WorldWideScience

Sample records for liposomal carrier systems

  1. Liposomes as potential carrier system for targeted delivery of polyene antibiotics.

    Science.gov (United States)

    Naik, Suresh R; Desai, Sandhya K; Shah, Priyank D; Wala, Santosh M

    2013-09-01

    The development of new therapeutic modalities involves the use of drug carrier, such as liposomes, which can modify pharmacokinetic and bio-distribution of drug profile. Polyene antibiotics incorporation into liposomes improves its availability at the site, bio-distribution and therapeutic index mainly through the engulfment of liposomes by circulating monocytes/macrophages and transportation to the site of infection. Polyene antibiotics (AmB, SJA-95, HA-1-92) and other antibiotics (streptomycin, tobramycin, quinolones, anti-tubercular and anti-cancer drugs), liposomal preparations are described with possible advantages from therapeutic efficacy and toxicity point of view. The polyene macrolide antibiotics liposomal preparations proved to be more effective in the treatment of systemic mycosis. The AmB-cyclodextrin derivatives inclusion complex is a major breakthrough in liposomal preparation which can be converted into aqueous phase of liposome. Liposomal drug incorporated preparation has been one of the important areas of research for developing the existing polyene antibiotics into useful chemotherapeutic agents in clinical medicine. In recent past other antibiotics have also been incorporated into liposomes using wide variety of materials, phosphatidylethanolamine derivatives (pegylated liposomes, enzyme sensitive conjugates, fluidosomes of anti-cancer drugs and poly lactic/glycolic acid microspheres for anti-tuberculosis drugs). In addition, attempts were also made to extend the receptor mediated drug targeting and to review some relevant patents.

  2. Carrier-inside-carrier: polyelectrolyte microcapsules as reservoir for drug-loaded liposomes.

    Science.gov (United States)

    Maniti, Ofelia; Rebaud, Samuel; Sarkis, Joe; Jia, Yi; Zhao, Jie; Marcillat, Olivier; Granjon, Thierry; Blum, Loïc; Li, Junbai; Girard-Egrot, Agnès

    2015-01-01

    Conventional liposomes have a short life-time in blood, unless they are protected by a polymer envelope, most often polyethylene glycol. However, these stabilizing polymers frequently interfere with cellular uptake, impede liposome-membrane fusion and inhibit escape of liposome content from endosomes. To overcome such drawbacks, polymer-based systems as carriers for liposomes are currently developed. Conforming to this approach, we propose a new and convenient method for embedding small size liposomes, 30-100 nm, inside porous calcium carbonate microparticles. These microparticles served as templates for deposition of various polyelectrolytes to form a protective shell. The carbonate particles were then dissolved to yield hollow polyelectrolyte microcapsules. The main advantage of using this method for liposome encapsulation is that carbonate particles can serve as a sacrificial template for deposition of virtually any polyelectrolyte. By carefully choosing the shell composition, bioavailability of the liposomes and of the encapsulated drug can be modulated to respond to biological requirements and to improve drug delivery to the cytoplasm and avoid endosomal escape.

  3. Development of Liposomal Bubbles with Perfluoropropane Gas as Gene Delivery Carriers

    Science.gov (United States)

    Maruyama, Kazuo; Suzuki, Ryo; Sawamura, Kaori; Takizawa, Tomoko; Utoguchi, Naoki; Negishi, Yoichi

    2007-05-01

    Liposomes have some advantages as drug, antigen and gene delivery carriers. Their size can be easily controlled and they can be modified to add a targeting function. Based on liposome technology, we developed novel liposomal bubbles (Bubble liposomes) containing the ultrasound imaging gas, perfluoropropane. We assessed the feasibility of Bubble liposomes as carriers for gene delivery after cavitation induced by ultrasound. At first, we investigated their ability to deliver genes with Bubble liposomes and ultrasound to various types of cells such as mouse sarcoma cells, mouse melanoma cells, human T cell line and human umbilical vein endothelial cells. The results showed that the Bubble liposomes could deliver plasmid DNA to many cell types without cytotoxicity. In addition, we found that Bubble liposomes could effectively deliver plasmid DNA into mouse femoral artery in vivo. The gene transduction with Bubble liposomes was more effectively than conventional lipofection. We conclude that Bubble liposomes are unique and efficient gene delivery carriers in vitro and in vivo.

  4. Preparation and investigation of Ulex europaeus agglutinin I-conjugated liposomes as potential oral vaccine carriers.

    Science.gov (United States)

    Li, KeXin; Chen, DaWei; Zhao, XiuLi; Hu, HaiYang; Yang, ChunRong; Pang, DaHai

    2011-11-01

    We prepared and optimized Ulex europaeus agglutinin I (UEAI)-modified Bovine serum albumin (BSA)-encapsulating liposomes (UEAI-LIP) as oral vaccine carriers and examined the feasibility of inducing systemic and mucosal immune responses by oral administration of UEAILIP. The prepared systems were characterized in vitro for their average size, zeta potential, encapsulation efficiency (EE%) and conjugation efficiency (CE%). In vitro release studies indicated that the presence of UEAI around the optimized liposomes was able to prevent a burst release of loaded BSA and provide sustained release of the encapsulated protein. In vivo immune-stimulating results in KM mice showed that BSA given intramuscularly generated systemic response only but both systemic and mucosal immune responses could be induced simultaneously in the groups in which BSA-loaded liposomes (LIP) and UEAI-LIP were administered intragastrically. Furthermore, the modification of UEAI on the surface of liposomes could further enhance the IgA and IgG levels obviously. In conclusion, this study demonstrated the high potential of lectin-modified liposomes containing the antigen as carriers for oral vaccine.

  5. Biotinylated liposomes as potential carriers for the oral delivery of insulin.

    Science.gov (United States)

    Zhang, Xingwang; Qi, Jianping; Lu, Yi; He, Wei; Li, Xiaoyang; Wu, Wei

    2014-01-01

    This study aimed to explore biotinylated liposomes (BLPs) as novel carriers to enhance the oral delivery of insulin. Biotinylation was achieved by incorporating biotin-conjugated phospholipids into the liposome membranes. A significant hypoglycemic effect and enhanced absorption were observed after treating diabetic rats with the BLPs with a relative bioavailability of 12.09% and 8.23%, based on the measurement of the pharmacologic effect and the blood insulin level, respectively; this achieved bioavailability was approximately double that of conventional liposomes. The significance of the biotinylation was confirmed by the facilitated absorption of the BLPs through receptor-mediated endocytosis, as well as by the improved physical stability of the liposomes. Increased cellular uptake and quick gastrointestinal transport further verified the ability of the BLPs to enhance absorption. These results provide a proof of concept that BLPs can be used as potential carriers for the oral delivery of insulin. Diabetes remains a major source of mortality in the Western world, and advances in its management are expected to have substantial socioeconomic impact. In this paper, biotinylated liposomes were utilized as carriers of insulin for local delivery, demonstrating the feasibility of this approach in a rat model. © 2014.

  6. Liposomal Conjugates for Drug Delivery to the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Frieder Helm

    2015-04-01

    Full Text Available Treatments of central nervous system (CNS diseases often fail due to the blood–brain barrier. Circumvention of this obstacle is crucial for any systemic treatment of such diseases to be effective. One approach to transfer drugs into the brain is the use of colloidal carrier systems—amongst others, liposomes. A prerequisite for successful drug delivery by colloidal carriers to the brain is the modification of their surface, making them invisible to the reticuloendothelial system (RES and to target them to specific surface epitopes at the blood–brain barrier. This study characterizes liposomes conjugated with cationized bovine serum albumin (cBSA as transport vectors in vitro in porcine brain capillary endothelial cells (PBCEC and in vivo in rats using fluorescently labelled liposomes. Experiments with PBCEC showed that sterically stabilized (PEGylated liposomes without protein as well as liposomes conjugated to native bovine serum albumin (BSA were not taken up. In contrast, cBSA-liposomes were taken up and appeared to be concentrated in intracellular vesicles. Uptake occurred in a concentration and time dependent manner. Free BSA and free cBSA inhibited uptake. After intravenous application of cBSA-liposomes, confocal fluorescence microscopy of brain cryosections from male Wistar rats showed fluorescence associated with liposomes in brain capillary surrounding tissue after 3, 6 and 24 h, for liposomes with a diameter between 120 and 150 nm, suggesting successful brain delivery of cationized-albumin coupled liposomes.

  7. Giant liposomes as delivery system for ecophysiological studies in copepods.

    Science.gov (United States)

    Buttino, Isabella; De Rosa, Giuseppe; Carotenuto, Ylenia; Ianora, Adrianna; Fontana, Angelo; Quaglia, Fabiana; La Rotonda, Maria Immacolata; Miralto, Antonio

    2006-03-01

    Giant liposomes are proposed as a potential delivery system in marine copepods, the dominant constituent of the zooplankton. Liposomes were prepared in the same size range as the food ingested by copepods (mean diameter of about 7 microm). The encapsulation of a hydrophilic and high molecular mass fluorescent compound, fluorescein isothiocyanate-dextran (FitcDx), within the liposomes provided a means of verifying copepod ingestion when viewed with the confocal laser-scanning microscope. Females of the calanoid copepod Temora stylifera were fed with FitcDx-encapsulated liposomes alone or mixed with the dinoflagellate alga Prorocentrum minimum. Control copepods were incubated with the P. minimum diet alone. Egg production rates, percentage egg-hatching success and number of faecal pellets produced were evaluated after 24 h and 48 h of feeding. Epifluorescence of copepod gut and faecal pellets indicated that the liposomes were actively ingested by T. stylifera in both experimental food conditions, with or without the dinoflagellate diet. Ingestion rates calculated using 3H-labelled liposomes indicated that females ingested more liposomes when P. minimum was added to the solution (16% vs 7.6% of uptake). When liposomes were supplied together with the algal diet, egg production rate, egg-hatching success and faecal pellet production were as high as those observed for the control diet. By contrary, egg production and hatching success were very low with a diet of liposomes alone and faecal pellet production was similar to that recorded in starved females. This results suggest that liposomes alone did not add any nutritive value to the diet, making them a good candidate as inert carriers to study the nutrient requirements or biological activity of different compounds. In particular, such liposomes are proposed as carriers for diatom-derived polyunsaturated aldehydes, which are known to impair copepod embryo viability. Other potential applications of liposomes as a delivery

  8. Liposome Delivery Systems for Inhalation: A Critical Review Highlighting Formulation Issues and Anticancer Applications.

    Science.gov (United States)

    Rudokas, Mindaugas; Najlah, Mohammad; Alhnan, Mohamed Albed; Elhissi, Abdelbary

    2016-01-01

    This is a critical review on research conducted in the field of pulmonary delivery of liposomes. Issues relating to the mechanism of nebulisation and liposome composition were appraised and correlated with literature reports of liposome formulations used in clinical trials to understand the role of liposome size and composition on therapeutic outcome. A major highlight was liposome inhalation for the treatment of lung cancers. Many in vivo studies that explored the potential of liposomes as anticancer carrier systems were evaluated, including animal studies and clinical trials. Liposomes can entrap anticancer drugs and localise their action in the lung following pulmonary delivery. The safety of inhaled liposomes incorporating anticancer drugs depends on the anticancer agent used and the amount of drug delivered to the target cancer in the lung. The difficulty of efficient targeting of liposomal anticancer aerosols to the cancerous tissues within the lung may result in low doses reaching the target site. Overall, following the success of liposomes as inhalable carriers in the treatment of lung infections, it is expected that more focus from research and development will be given to designing inhalable liposome carriers for the treatment of other lung diseases, including pulmonary cancers. The successful development of anticancer liposomes for inhalation may depend on the future development of effective aerosolisation devices and better targeted liposomes to maximise the benefit of therapy and reduce the potential for local and systemic adverse effects. © 2016 S. Karger AG, Basel.

  9. MITO-Porter: A liposome-based carrier system for delivery of macromolecules into mitochondria via membrane fusion.

    Science.gov (United States)

    Yamada, Yuma; Akita, Hidetaka; Kamiya, Hiroyuki; Kogure, Kentaro; Yamamoto, Takenori; Shinohara, Yasuo; Yamashita, Kikuji; Kobayashi, Hideo; Kikuchi, Hiroshi; Harashima, Hideyoshi

    2008-02-01

    Mitochondria are the principal producers of energy in higher cells. Mitochondrial dysfunction is implicated in a variety of human diseases, including cancer and neurodegenerative disorders. Effective medical therapies for such diseases will ultimately require targeted delivery of therapeutic proteins or nucleic acids to the mitochondria, which will be achieved through innovations in the nanotechnology of intracellular trafficking. Here we describe a liposome-based carrier that delivers its macromolecular cargo to the mitochondrial interior via membrane fusion. These liposome particles, which we call MITO-Porters, carry octaarginine surface modifications to stimulate their entry into cells as intact vesicles (via macropinocytosis). We identified lipid compositions for the MITO-Porter which promote both its fusion with the mitochondrial membrane and the release of its cargo to the intra-mitochondrial compartment in living cells. Thus, the MITO-Porter holds promise as an efficacious system for the delivery of both large and small therapeutic molecules into mitochondria.

  10. Evaluation of the physicochemical properties of liposomes as potential carriers of anticancer drugs: spectroscopic study

    International Nuclear Information System (INIS)

    Pentak, Danuta

    2016-01-01

    Vesicle size and composition are a critical parameter for determining the circulation half-life of liposomes. Size influences the degree of drug encapsulation in liposomes. The geometry, size, and properties of liposomes in an aqueous environment have to be described to enable potential applications of liposome systems as drug carriers. The characteristics of multiple thermotropic phase transitions are also an important consideration in liposomes used for analytical and bioanalytical purposes. The aim of this study was to evaluate the physicochemical properties of liposomes which accommodate hydrophilic and amphiphilic drugs used in cancer therapy. The studied liposomes were prepared with the involvement of the modified reverse-phase evaporation method (mREV). The prepared liposomes had a diameter of 70–150 nm. The analyzed compounds were 1-β-d-arabinofuranosylcytosine, cyclophosphamide, and ifosfamide. In literature, there is no information about simultaneous incorporation of cytarabine, ifosfamide, and cyclophosphamide, in spite of the fact that these drugs have been used for more than 30 years. A combination of the examined drugs is used in CODOX-M/IVAC therapy. CODOX-M/IVAC (cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine) is one of the currently preferred intensive-dose chemotherapy regimens for Burkitt lymphoma (BL). The present research demonstrates the pioneering studies of incorporation of ifosfamide into liposome vesicles, location of and competition between the analyzed drugs and liposome vesicles. The applied methods were nuclear magnetic resonance (NMR), atomic force microscopy (AFM), differential scanning calorimetry (DSC).Graphical Abstract.

  11. Evaluation of the physicochemical properties of liposomes as potential carriers of anticancer drugs: spectroscopic study

    Energy Technology Data Exchange (ETDEWEB)

    Pentak, Danuta, E-mail: danuta.pentak@us.edu.pl [University of Silesia, Department of Materials Chemistry and Chemical Technology, Institute of Chemistry (Poland)

    2016-05-15

    Vesicle size and composition are a critical parameter for determining the circulation half-life of liposomes. Size influences the degree of drug encapsulation in liposomes. The geometry, size, and properties of liposomes in an aqueous environment have to be described to enable potential applications of liposome systems as drug carriers. The characteristics of multiple thermotropic phase transitions are also an important consideration in liposomes used for analytical and bioanalytical purposes. The aim of this study was to evaluate the physicochemical properties of liposomes which accommodate hydrophilic and amphiphilic drugs used in cancer therapy. The studied liposomes were prepared with the involvement of the modified reverse-phase evaporation method (mREV). The prepared liposomes had a diameter of 70–150 nm. The analyzed compounds were 1-β-d-arabinofuranosylcytosine, cyclophosphamide, and ifosfamide. In literature, there is no information about simultaneous incorporation of cytarabine, ifosfamide, and cyclophosphamide, in spite of the fact that these drugs have been used for more than 30 years. A combination of the examined drugs is used in CODOX-M/IVAC therapy. CODOX-M/IVAC (cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine) is one of the currently preferred intensive-dose chemotherapy regimens for Burkitt lymphoma (BL). The present research demonstrates the pioneering studies of incorporation of ifosfamide into liposome vesicles, location of and competition between the analyzed drugs and liposome vesicles. The applied methods were nuclear magnetic resonance (NMR), atomic force microscopy (AFM), differential scanning calorimetry (DSC).Graphical Abstract.

  12. Interactions of liposome carriers with infectious fungal hyphae reveals the role of β-glucans.

    Science.gov (United States)

    Chavan, Neelam L; Young, Joseph K; Drezek, Rebekah A; Lewis, Russell; Bikram, Malavosklish

    2012-09-04

    Relatively little is known about how liposomal formulations modulate drug delivery to fungal pathogens. We compared patterns of hyphal cell wall binding for empty rhodmine-labeled liposomes and the clinically available amphotericin B-containing liposomal formulation (AmBisome) in Aspergillus fumigatus and Candida albicans. Following 0.5 h of coincubation with A. fumigatus , empty liposomes concentrated primarily in fungal septae along at the surface of the cell wall, suggesting that liposome uptake is concentrated in areas of the cell wall where linear glucan is exposed on the cell surface, which was confirmed by aniline blue staining. Consistent with this hypothesis, pretreatment of liposomes with soluble linear glucan (laminarin) decreased liposome binding in both Aspergillus and Candida fungal hyphae, while growth of Aspergillus hyphae in the presence of an agent that increases fungal cell wall surface exposure of linear β-glucans without cell death (caspofungin) increased liposome uptake throughout the Aspergillus fungal cell wall. Increasing the polyethylene glycol (PEG) concentration in liposomes from 0 to 30% significantly increased fungal uptake of liposomes that was only modestly attenuated when fungal cells were incubated in serum concentrations ranging from 10 to 100%. The presence of β-glucans on the fungal hyphae cell walls of Aspergillus fumigatus is one of the factors responsible for mediating the binding of liposome carriers to the hyphae and could explain possible synergy reported between liposomal amphotericin B and echinocanins.

  13. Using liposomes as carriers for polyphenolic compounds: the case of trans-resveratrol.

    Directory of Open Access Journals (Sweden)

    Claudia Bonechi

    Full Text Available Resveratrol (3,5,4'-trihydroxy-trans-stilbene is a polyphenol found in various plants, especially in the skin of red grapes. The effect of resveratrol on human health is the topic of numerous studies. In fact this molecule has shown anti-cancer, anti-inflammatory, blood-sugar-lowering ability and beneficial cardiovascular effects. However, for many polyphenol compounds of natural origin bioavailability is limited by low solubility in biological fluids, as well as by rapid metabolization in vivo. Therefore, appropriate carriers are required to obtain efficient therapeutics along with low administration doses.Liposomes are excellent candidates for drug delivery purposes, due to their biocompatibility, wide choice of physico-chemical properties and easy preparation.In this paper liposome formulations made by a saturated phosphatidyl-choline (DPPC and cholesterol (or its positively charged derivative DC-CHOL were chosen to optimize the loading of a rigid hydrophobic molecule such as resveratrol.Plain and resveratrol loaded liposomes were characterized for size, surface charge and structural details by complementary techniques, i.e. Dynamic Light Scattering (DLS, Zeta potential and Small Angle X-ray Scattering (SAXS. Nuclear and Electron Spin magnetic resonances (NMR and ESR, respectively were also used to gain information at the molecular scale.The obtained results allowed to give an account of loaded liposomes in which resveratrol interacted with the bilayer, being more deeply inserted in cationic liposomes than in zwitterionic liposomes. Relevant properties such as the mean size and the presence of oligolamellar structures were influenced by the loading of RESV guest molecules.The toxicity of all these systems was tested on stabilized cell lines (mouse fibroblast NIH-3T3 and human astrocytes U373-MG, showing that cell viability was not affected by the administration of liposomial resveratrol.

  14. Liposomes as carriers of imaging agents

    International Nuclear Information System (INIS)

    Caride, V.J.

    1985-01-01

    This review discusses the utilization of liposomes as imaging agents or as vehicles for contrast materials. The initial approach was the use of radiolabeled liposomes for scintigraphy. To this end liposomes were either labeled in the lipid membrane or aqueous radiotracers were incorporated inside the lipid vesicles. The lipid labeling provides a more stable association of the radioactive tracer and the lipid vesicles, while the use of water-soluble radiotracers provides a wider selection of compounds. Early attempts at selective tumor imaging using radiolabeled liposomes were unsuccessful. The use of monoclonal antibodies attached to liposomes offers new hopes. Several strategies have been proposed in this respect and several others can be envisioned. The use of liposomes permits the use of several administration routes for imaging agents. Of particular interest is the subcutaneous administration for lymph node visualization. Liposomes offer clear advantages over most radiocontrast agents for prolonged hepatosplenic contrast enhancement. This is particularly relevant in the diagnostic evaluation of the abdomen with computed tomography. Important research efforts are being conducted in this area. Two different approaches have been advanced: the incorporation of contrast agents into liposomes and the preparation of radiopaque liposomes from radiodense lipids. Nuclear magnetic resonance imaging can also benefit from contrast agents. Several centers are investigating this exciting field using liposomes loaded with paramagnetic elements.152 references

  15. Molecular Dynamics Studies of Liposomes as Carriers for Photosensitizing Drugs: Development, Validation, and Simulations with a Coarse-Grained Model.

    Science.gov (United States)

    Jämbeck, Joakim P M; Eriksson, Emma S E; Laaksonen, Aatto; Lyubartsev, Alexander P; Eriksson, Leif A

    2014-01-14

    Liposomes are proposed as drug delivery systems and can in principle be designed so as to cohere with specific tissue types or local environments. However, little detail is known about the exact mechanisms for drug delivery and the distributions of drug molecules inside the lipid carrier. In the current work, a coarse-grained (CG) liposome model is developed, consisting of over 2500 lipids, with varying degrees of drug loading. For the drug molecule, we chose hypericin, a natural compound proposed for use in photodynamic therapy, for which a CG model was derived and benchmarked against corresponding atomistic membrane bilayer model simulations. Liposomes with 21-84 hypericin molecules were generated and subjected to 10 microsecond simulations. Distribution of the hypericins, their orientations within the lipid bilayer, and the potential of mean force for transferring a hypericin molecule from the interior aqueous "droplet" through the liposome bilayer are reported herein.

  16. Mechanism and kinetics of the loss of poorly soluble drugs from liposomal carriers studied by a novel flow field-flow fractionation-based drug release-/transfer-assay

    DEFF Research Database (Denmark)

    Hinna, Askell Hvid; Hupfeld, Stefan; Kuntsche, Judith

    2016-01-01

    Liposomes represent a versatile drug formulation approach e.g. for improving the water-solubility of poorly soluble drugs but also to achieve drug targeting and controlled release. For the latter applications it is essential that the drug remains associated with the liposomal carrier during transit...... in the vascular bed. A range of in vitro test methods has been suggested over the years for prediction of the release of drug from liposomal carriers. The majority of these fail to give a realistic prediction for poorly water-soluble drugs due to the intrinsic tendency of such compounds to remain associated...... the amount of drug remaining associated with the liposomal drug carrier as well as that transferred to the acceptor liposomes at distinct times of incubation, boththe kinetics of drug transfer and release to the water phase could be established for the model drug p-THPP (5,10,15,20-tetrakis(4-hydroxyphenyl...

  17. [Drug delivery systems using nano-sized drug carriers].

    Science.gov (United States)

    Nakayama, Masamichi; Okano, Teruo

    2005-07-01

    Nanotechnology has attracted great attention all over the world in recent several years and has led to the establishment of the novel technical field of "nanomedicine" through collaboration with advanced medical technology. Particularly, site-specific drug targeting using particle drug carrier systems has made substantial progress and been actively developed. This review explains the essential factors (size and chemical character) of drug carriers to allow long circulation in the bloodstream avoiding the reticuloendothelial system, and shows the present status and future perspective of several types of nano-carrier systems (water-soluble polymer, liposome and polymeric micelle). We also introduce the novel concept of multi-targeting system (combination of two or more targeting methodologies) for ideal drug therapies.

  18. Elastic liposomes as novel carriers: recent advances in drug delivery

    Directory of Open Access Journals (Sweden)

    Hussain A

    2017-07-01

    Full Text Available Afzal Hussain,1,2 Sima Singh,1 Dinesh Sharma,3 Thomas J Webster,4 Kausar Shafaat,2 Abdul Faruk5 1Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India; 2Faculty of Pharmacy, Sachchidananda Sinha College, Aurangabad, Bihar, India; 3Zifam Pyrex Myanmar Co. Ltd., Yangon, Myanmar; 4Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 5Department of Pharmaceutical Sciences, Hemwati Nandan Bahuguna Garhwal University, Srinagar, Uttarakhand, India Abstract: Elastic liposomes (EL are some of the most versatile deformable vesicular carriers that comprise physiologically biocompatible lipids and surfactants for the delivery of numerous challenging molecules and have marked advantages over other colloidal systems. They have been investigated for a wide range of applications in pharmaceutical technology through topical, transdermal, nasal, and oral routes for efficient and effective drug delivery. Increased drug encapsulation efficiency, enhanced drug permeation and penetration into or across the skin, and ultradeformability have led to widespread interest in ELs to modulate drug release, permeation, and drug action more efficiently than conventional drug-release vehicles. This review provides insights into the versatile role that ELs play in the delivery of numerous drugs and biomolecules by improving drug release, permeation, and penetration across the skin as well as stability. Furthermore, it provides future directions that should ensure the widespread use of ELs across all medical fields. Keywords: elastic liposomes, drug delivery, topical, transdermal, enhanced delivery 

  19. Elastic liposomes as novel carriers: recent advances in drug delivery

    Science.gov (United States)

    Hussain, Afzal; Singh, Sima; Sharma, Dinesh; Webster, Thomas J; Shafaat, Kausar; Faruk, Abdul

    2017-01-01

    Elastic liposomes (EL) are some of the most versatile deformable vesicular carriers that comprise physiologically biocompatible lipids and surfactants for the delivery of numerous challenging molecules and have marked advantages over other colloidal systems. They have been investigated for a wide range of applications in pharmaceutical technology through topical, transdermal, nasal, and oral routes for efficient and effective drug delivery. Increased drug encapsulation efficiency, enhanced drug permeation and penetration into or across the skin, and ultradeformability have led to widespread interest in ELs to modulate drug release, permeation, and drug action more efficiently than conventional drug-release vehicles. This review provides insights into the versatile role that ELs play in the delivery of numerous drugs and biomolecules by improving drug release, permeation, and penetration across the skin as well as stability. Furthermore, it provides future directions that should ensure the widespread use of ELs across all medical fields. PMID:28761343

  20. Delivery systems for biopharmaceuticals. Part II: Liposomes, Micelles, Microemulsions and Dendrimers.

    Science.gov (United States)

    Silva, Ana C; Lopes, Carla M; Lobo, José M S; Amaral, Maria H

    2015-01-01

    Biopharmaceuticals are a generation of drugs that include peptides, proteins, nucleic acids and cell products. According to their particular molecular characteristics (e.g. high molecular size, susceptibility to enzymatic activity), these products present some limitations for administration and usually parenteral routes are the only option. To avoid these limitations, different colloidal carriers (e.g. liposomes, micelles, microemulsions and dendrimers) have been proposed to improve biopharmaceuticals delivery. Liposomes are promising drug delivery systems, despite some limitations have been reported (e.g. in vivo failure, poor long-term stability and low transfection efficiency), and only a limited number of formulations have reached the market. Micelles and microemulsions require more studies to exclude some of the observed drawbacks and guarantee their potential for use in clinic. According to their peculiar structures, dendrimers have been showing good results for nucleic acids delivery and a great development of these systems during next years is expected. This is the Part II of two review articles, which provides the state of the art of biopharmaceuticals delivery systems. Part II deals with liposomes, micelles, microemulsions and dendrimers.

  1. Liposome-based drug delivery in breast cancer treatment

    International Nuclear Information System (INIS)

    Park, John W

    2002-01-01

    Drug delivery systems can in principle provide enhanced efficacy and/or reduced toxicity for anticancer agents. Long circulating macromolecular carriers such as liposomes can exploit the 'enhanced permeability and retention' effect for preferential extravasation from tumor vessels. Liposomal anthracyclines have achieved highly efficient drug encapsulation, resulting in significant anticancer activity with reduced cardiotoxicity, and include versions with greatly prolonged circulation such as liposomal daunorubicin and pegylated liposomal doxorubicin. Pegylated liposomal doxorubucin has shown substantial efficacy in breast cancer treatment both as monotherapy and in combination with other chemotherapeutics. Additional liposome constructs are being developed for the delivery of other drugs. The next generation of delivery systems will include true molecular targeting; immunoliposomes and other ligand-directed constructs represent an integration of biological components capable of tumor recognition with delivery technologies

  2. Chitosan/lecithin liposomal nanovesicles as an oral insulin delivery system.

    Science.gov (United States)

    Al-Remawi, Mayyas; Elsayed, Amani; Maghrabi, Ibrahim; Hamaidi, Mohammad; Jaber, Nisrein

    2017-05-01

    In the present work, insulin-chitosan polyelectrolyte complexes associated to lecithin liposomes were investigated as a new carrier for oral delivery of insulin. The preparation was characterized in terms of particle size, zeta potential and encapsulation efficiency. Surface tension measurements revealed that insulin-chitosan polyelectrolyte complexes have some degree of hydrophobicity and should be added to lecithin liposomal dispersion and not the vice versa to prevent their adsorption on the surface. Stability of insulin was enhanced when it was associated to liposomes. Significant reduction of blood glucose levels was noticed after oral administration of liposomal preparation to streptozotocin diabetic rats compared to control. The hypoglycemic activity was more prolonged compared to subcutaneously administered insulin.

  3. Mechanism and kinetics of the loss of poorly soluble drugs from liposomal carriers studied by a novel flow field-flow fractionation-based drug release-/transfer-assay.

    Science.gov (United States)

    Hinna, Askell Hvid; Hupfeld, Stefan; Kuntsche, Judith; Bauer-Brandl, Annette; Brandl, Martin

    2016-06-28

    Liposomes represent a versatile drug formulation approach e.g. for improving the water-solubility of poorly soluble drugs but also to achieve drug targeting and controlled release. For the latter applications it is essential that the drug remains associated with the liposomal carrier during transit in the vascular bed. A range of in vitro test methods has been suggested over the years for prediction of the release of drug from liposomal carriers. The majority of these fail to give a realistic prediction for poorly water-soluble drugs due to the intrinsic tendency of such compounds to remain associated with liposome bilayers even upon extensive dilution. Upon i.v. injection, in contrast, rapid drug loss often occurs due to drug transfer from the liposomal carriers to endogenous lipophilic sinks such as lipoproteins, plasma proteins or membranes of red blood cells and endothelial cells. Here we report on the application of a recently introduced in vitro predictive drug transfer assay based on incubation of the liposomal drug carrier with large multilamellar liposomes, the latter serving as a biomimetic model sink, using flow field-flow fractionation as a tool to separate the two types of liposomes. By quantifying the amount of drug remaining associated with the liposomal drug carrier as well as that transferred to the acceptor liposomes at distinct times of incubation, both the kinetics of drug transfer and release to the water phase could be established for the model drug p-THPP (5,10,15,20-tetrakis(4-hydroxyphenyl)21H,23H-porphine). p-THPP is structurally similar to temoporfin, a photosensitizer which is under clinical evaluation in a liposomal formulation. Mechanistic insights were gained by varying the donor-to-acceptor lipid mass ratio, size and lamellarity of the liposomes. Drug transfer kinetics from one liposome to another was found rate determining as compared to redistribution from the outermost to the inner concentric bilayers, such that the overall

  4. Liposomes - experiment of magnetic resonance imaging application

    International Nuclear Information System (INIS)

    Mathieu, S.

    1987-01-01

    Most pharmaceutical research effort with liposomes has been involved with the investigation of their use as drug carriers to particular target organs. Recently there has been a growing interest in liposomes not only as carrier of drugs but as a tool for the introduction of various substances into the human body. In this study, liposome delivery of nitroxyl radicals as NMR contrast agent for improved tissue imaging is experimented in rats [fr

  5. Recent advances on liposomal nanoparticles: synthesis, characterization and biomedical applications.

    Science.gov (United States)

    Panahi, Yunes; Farshbaf, Masoud; Mohammadhosseini, Majid; Mirahadi, Mozhdeh; Khalilov, Rovshan; Saghfi, Siamak; Akbarzadeh, Abolfazl

    2017-06-01

    Liposome is a new nanostructure for the encapsulation and delivery of bioactive agents. There are a lot of bioactive materials that could be incorporated into liposomes including cosmetics, food ingredients, and pharmaceuticals. Liposomes possess particular properties such as biocompatibility, biodegradability; accompanied by their nanosize they have potential applications in nanomedicine, cosmetics, and food industry. Nanoliposome technology offers thrilling chances for food technologists in fields including encapsulation and controlled release of food ingredients, also improved bioavailability and stability of sensitive materials. Amid numerous brilliant new drug and gene delivery systems, liposomes provide an advanced technology to carry active molecules to the specific site of action, and now days, various formulations are in clinical use. In this paper, we provide review of the main physicochemical properties of liposomes, current methods of the manufacturing and introduce some of their usage in food nanotechnology as carrier vehicles of nutrients, enzymes, and food antimicrobials and their applications as drug carriers and gene delivery agents in biomedicine.

  6. Liposomal drug delivery system from laboratory to clinic

    Directory of Open Access Journals (Sweden)

    Kshirsagar N

    2005-01-01

    Full Text Available The main objective of drug delivery systems is to deliver a drug effectively, specifically to the site of action and to achieve greater efficacy and minimise the toxic effects compared to conventional drugs. Amongst various carrier systems, liposomes have generated a great interest because of their versatility. Liposomes are vesicular concentric bilayered structures, which are biocompatible, biodegradable and nonimmumnogenic. They can control the delivery of drugs by targeting the drug to the site of action or by site avoidance drug delivery or by prolonged circulation of drugs. Amphotericin B (Amp B remains the drug of choice in most systemic mycoses and also as a second line treatment for Kala azar. However, its toxic effects often limit its use. Although the liposome delivery system has been tried for several drugs, only a few have been used in patients due to the slow development of necessary large-scale pharmaceutical procedures. This paper reviews the development of the technique for liposomal Amphotericin B (L-Amp-LRC-1, FungisomeTM drug delivery system in our laboratory in collaboration with the department of Biochemistry, Delhi University in India and proving the safety and efficacy of this preparation in clinical practice. It also attempts to compare the efficacy and benefits of our product for Indian patients with those of similar products and it includes facts from the publications that flowed from our work. As compared to conventional Amp B, Fungisome is infused over a much shorter period requiring a smaller volume and no premedication. It was found to be safe in patients who had developed serious unacceptable toxicity with conventional Amp B. In renal transplant patients, Fungisome did not produce any nephrotoxicity. Fungisome is effective in fungal infections resistant to fluconazole, conventional Amp B and in virgin and resistant cases of visceral leishmaniasis. The cost of any drug is of great significance, especially in India

  7. Mucosal delivery of liposome-chitosan nanoparticle complexes.

    Science.gov (United States)

    Carvalho, Edison L S; Grenha, Ana; Remuñán-López, Carmen; Alonso, Maria José; Seijo, Begoña

    2009-01-01

    Designing adequate drug carriers has long been a major challenge for those working in drug delivery. Since drug delivery strategies have evolved for mucosal delivery as the outstanding alternative to parenteral administration, many new drug delivery systems have been developed which evidence promising properties to address specific issues. Colloidal carriers, such as nanoparticles and liposomes, have been referred to as the most valuable approaches, but still have some limitations that can become more inconvenient as a function of the specific characteristics of administration routes. To overcome these limitations, we developed a new drug delivery system that results from the combination of chitosan nanoparticles and liposomes, in an approach of combining their advantages, while avoiding their individual limitations. These lipid/chitosan nanoparticle complexes are, thus, expected to protect the encapsulated drug from harsh environmental conditions, while concomitantly providing its controlled release. To prepare these assemblies, two different strategies have been applied: one focusing on the simple hydration of a previously formed dry lipid film with a suspension of chitosan nanoparticles, and the other relying on the lyophilization of both basic structures (nanoparticles and liposomes) with a subsequent step of hydration with water. The developed systems are able to provide a controlled release of the encapsulated model peptide, insulin, evidencing release profiles that are dependent on their lipid composition. Moreover, satisfactory in vivo results have been obtained, confirming the potential of these newly developed drug delivery systems as drug carriers through distinct mucosal routes.

  8. Hydrophobic Drug-Loaded PEGylated Magnetic Liposomes for Drug-Controlled Release

    Science.gov (United States)

    Hardiansyah, Andri; Yang, Ming-Chien; Liu, Ting-Yu; Kuo, Chih-Yu; Huang, Li-Ying; Chan, Tzu-Yi

    2017-05-01

    Less targeted and limited solubility of hydrophobic-based drug are one of the serious obstacles in drug delivery system. Thus, new strategies to enhance the solubility of hydrophobic drug and controlled release behaviors would be developed. Herein, curcumin, a model of hydrophobic drug, has been loaded into PEGylated magnetic liposomes as a drug carrier platform for drug controlled release system. Inductive magnetic heating (hyperthermia)-stimulated drug release, in vitro cellular cytotoxicity assay of curcumin-loaded PEGylated magnetic liposomes and cellular internalization-induced by magnetic guidance would be investigated. The resultant of drug carriers could disperse homogeneously in aqueous solution, showing a superparamagnetic characteristic and could inductive magnetic heating with external high-frequency magnetic field (HFMF). In vitro curcumin release studies confirmed that the drug carriers exhibited no significant release at 37 °C, whereas exhibited rapid releasing at 45 °C. However, it would display enormous (three times higher) curcumin releasing under the HFMF exposure, compared with that without HFMF exposure at 45 °C. In vitro cytotoxicity test shows that curcumin-loaded PEGylated magnetic liposomes could efficiently kill MCF-7 cells in parallel with increasing curcumin concentration. Fluorescence microscopy observed that these drug carriers could internalize efficiently into the cellular compartment of MCF-7 cells. Thus, it would be anticipated that the novel hydrophobic drug-loaded PEGylated magnetic liposomes in combination with inductive magnetic heating are promising to apply in the combination of chemotherapy and thermotherapy for cancer therapy.

  9. Nanostructured lipid carriers system: recent advances in drug delivery.

    Science.gov (United States)

    Iqbal, Md Asif; Md, Shadab; Sahni, Jasjeet Kaur; Baboota, Sanjula; Dang, Shweta; Ali, Javed

    2012-12-01

    Nanostructured lipid carrier (NLC) is second generation smarter drug carrier system having solid matrix at room temperature. This carrier system is made up of physiological, biodegradable and biocompatible lipid materials and surfactants and is accepted by regulatory authorities for application in different drug delivery systems. The availability of many products in the market in short span of time reveals the success story of this delivery system. Since the introduction of the first product, around 30 NLC preparations are commercially available. NLC exhibit superior advantages over other colloidal carriers viz., nanoemulsions, polymeric nanoparticles, liposomes, SLN etc. and thus, have been explored to more extent in pharmaceutical technology. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes NLC versatile delivery system for various routes of administration. The present review gives insights on the definitions and characterization of NLC as colloidal carriers including the production techniques and suitable formulations. This review paper also highlights the importance of NLC in pharmaceutical applications for the various routes of drug delivery viz., topical, oral, pulmonary, ocular and parenteral administration and its future perspective as a pharmaceutical carrier.

  10. Liposomal photosensitizers: potential platforms for anticancer photodynamic therapy

    Directory of Open Access Journals (Sweden)

    L.A. Muehlmann

    2011-08-01

    Full Text Available Photodynamic therapy is a well-established and clinically approved treatment for several types of cancer. Antineoplastic photodynamic therapy is based on photosensitizers, i.e., drugs that absorb photons translating light energy into a chemical potential that damages tumor tissues. Despite the encouraging clinical results with the approved photosensitizers available today, the prolonged skin phototoxicity, poor selectivity for diseased tissues, hydrophobic nature, and extended retention in the host organism shown by these drugs have stimulated researchers to develop new formulations for photodynamic therapy. In this context, due to their amphiphilic characteristic (compatibility with both hydrophobic and hydrophilic substances, liposomes have proven to be suitable carriers for photosensitizers, improving the photophysical properties of the photosensitizers. Moreover, as nanostructured drug delivery systems, liposomes improve the efficiency and safety of antineoplastic photodynamic therapy, mainly by the classical phenomenon of extended permeation and retention. Therefore, the association of photosensitizers with liposomes has been extensively studied. In this review, both current knowledge and future perspectives on liposomal carriers for antineoplastic photodynamic therapy are critically discussed.

  11. Tumor targeting using liposomal antineoplastic drugs

    Directory of Open Access Journals (Sweden)

    Jörg Huwyler

    2008-03-01

    Full Text Available Jörg Huwyler1, Jürgen Drewe2, Stephan Krähenbühl21University of Applied Sciences Northwestern Switzerland, Institute of Pharma Technology, Muttenz, Switzerland; 2Department of Research and Division of Clinical Pharmacology, University Hospital Basel, Basel, SwitzerlandAbstract: During the last years, liposomes (microparticulate phospholipid vesicles have beenused with growing success as pharmaceutical carriers for antineoplastic drugs. Fields of application include lipid-based formulations to enhance the solubility of poorly soluble antitumordrugs, the use of pegylated liposomes for passive targeting of solid tumors as well as vector-conjugated liposomal carriers for active targeting of tumor tissue. Such formulation and drug targeting strategies enhance the effectiveness of anticancer chemotherapy and reduce at the same time the risk of toxic side-effects. The present article reviews the principles of different liposomal technologies and discusses current trends in this field of research.Keywords: tumor targeting, antineoplastic drugs, liposomes, pegylation, steric stabilization, immunoliposomes

  12. Nanodrug-enhanced radiofrequency tumor ablation: effect of micellar or liposomal carrier on drug delivery and treatment efficacy.

    Directory of Open Access Journals (Sweden)

    Marwan Moussa

    Full Text Available To determine the effect of different drug-loaded nanocarriers (micelles and liposomes on delivery and treatment efficacy for radiofrequency ablation (RFA combined with nanodrugs.Fischer 344 rats were used (n = 196. First, single subcutaneous R3230 tumors or normal liver underwent RFA followed by immediate administration of i.v. fluorescent beads (20, 100, and 500 nm, with fluorescent intensity measured at 4-24 hr. Next, to study carrier type on drug efficiency, RFA was combined with micellar (20 nm or liposomal (100 nm preparations of doxorubicin (Dox; targeting HIF-1α or quercetin (Qu; targeting HSP70. Animals received RFA alone, RFA with Lipo-Dox or Mic-Dox (1 mg i.v., 15 min post-RFA, and RFA with Lipo-Qu or Mic-Qu given 24 hr pre- or 15 min post-RFA (0.3 mg i.v.. Tumor coagulation and HIF-1α or HSP70 expression were assessed 24 hr post-RFA. Third, the effect of RFA combined with i.v. Lipo-Dox, Mic-Dox, Lipo-Qu, or Mic-Qu (15 min post-RFA compared to RFA alone on tumor growth and animal endpoint survival was evaluated. Finally, drug uptake was compared between RFA/Lipo-Dox and RFA/Mic-Dox at 4-72 hr.Smaller 20 nm beads had greater deposition and deeper tissue penetration in both tumor (100 nm/500 nm and liver (100 nm (p<0.05. Mic-Dox and Mic-Qu suppressed periablational HIF-1α or HSP70 rim thickness more than liposomal preparations (p<0.05. RFA/Mic-Dox had greater early (4 hr intratumoral doxorubicin, but RFA/Lipo-Dox had progressively higher intratumoral doxorubicin at 24-72 hr post-RFA (p<0.04. No difference in tumor growth and survival was seen between RFA/Lipo-Qu and RFA/Mic-Qu. Yet, RFA/Lipo-Dox led to greater animal endpoint survival compared to RFA/Mic-Dox (p<0.03.With RF ablation, smaller particle micelles have superior penetration and more effective local molecular modulation. However, larger long-circulating liposomal carriers can result in greater intratumoral drug accumulation over time and reduced tumor growth. Accordingly

  13. Recent advances in liposomal nanohybrid cerasomes as promising drug nanocarriers.

    Science.gov (United States)

    Yue, Xiuli; Dai, Zhifei

    2014-05-01

    Liposomes have been extensively investigated as possible carriers for diagnostic or therapeutic agents due to their unique properties. However, liposomes still have not attained their full potential as drug and gene delivery vehicles because of their insufficient morphological stability. Recently, a super-stable and freestanding hybrid liposomal cerasome (partially ceramic- or silica-coated liposome) has drawn much attention as a novel drug delivery system because its atomic layer of polyorganosiloxane surface imparts higher morphological stability than conventional liposomes and its liposomal bilayer structure reduces the overall rigidity and density greatly compared to silica nanoparticles. Cerasomes are more biocompatible than silica nanoparticles due to the incorporation of the liposomal architecture into cerasomes. Cerasomes combine the advantages of both liposomes and silica nanoparticles but overcome their disadvantages so cerasomes are ideal drug delivery systems. The present review will first highlights some of the key advances of the past decade in the technology of cerasome production and then review current biomedical applications of cerasomes, with a view to stimulating further research in this area of study. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

    Directory of Open Access Journals (Sweden)

    Ludmila Škorpilová

    2017-07-01

    Full Text Available Like thapsigargin, which is undergoing clinical trials, trilobolide is a natural product with promising anticancer and anti-inflammatory properties. Similar to thapsigargin, it has limited aqueous solubility that strongly reduces its potential medicinal applications. The targeted delivery of hydrophobic drugs can be achieved using liposome-based carriers. Therefore, we designed a traceable liposomal drug delivery system for trilobolide. The fluorescent green-emitting dye BODIPY, cholesterol and trilobolide were used to create construct 6. The liposomes were composed of dipalmitoyl-3-trimethylammoniumpropane and phosphatidylethanolamine. The whole system was characterized by atomic force microscopy, the average size of the liposomes was 150 nm in width and 30 nm in height. We evaluated the biological activity of construct 6 and its liposomal formulation, both of which showed immunomodulatory properties in primary rat macrophages. The uptake and intracellular distribution of construct 6 and its liposomal formulation was monitored by means of live-cell fluorescence microscopy in two cancer cell lines. The encapsulation of construct 6 into the liposomes improved the drug distribution in cancer cells and was followed by cell death. This new liposomal trilobolide derivative not only retains the biological properties of pure trilobolide, but also enhances the bioavailability, and thus has potential for the use in theranostic applications.

  15. Hyaluronan-decorated liposomes as drug delivery systems for cutaneous administration.

    Science.gov (United States)

    Franzé, Silvia; Marengo, Alessandro; Stella, Barbara; Minghetti, Paola; Arpicco, Silvia; Cilurzo, Francesco

    2018-01-15

    The work aimed to evaluate the feasibility to design hyaluronic acid (HA) decorated flexible liposomes to enhance the skin penetration of nifedipine. Egg phosphatidylcholine (e-PC) based transfersomes (Tween 80) and transethosomes (ethanol) were prepared. HA was reacted with 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (HA-DPPE) and two molar ratios (0.5 and 3%) of conjugate with respect to e-PC were tested. The presence of HA significantly increased the packing order of the bilayer (as verified by differential scanning calorimetry), reducing both the encapsulation efficiency and the flexibility of the decorated liposomes in a dose-dependent manner. In fact, at the highest HA content the constant of deformability (K, N/mm) increased and the carriers remained on the skin surface after topical application. The stiffening effect of HA was counterbalanced by the addition of ethanol as fluidizing agent that allowed to maintain the highest HA concentration, meanwhile reducing the K value of the vesicles. HA-transethosomes allowed a suitable nifedipine permeation (J ∼ 30 ng/cm 2 /h) and significantly improved the drug penetration, favouring the formation of a drug depot in the epidermis. These data suggest the potentialities of HA-transethosomes as drug delivery systems intended for the treatment of cutaneous pathologies and underline the importance of studying the effect of surface functionalization on carrier deformability to rationalize the design of such systems. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Experimental Aspects of Colloidal Interactions in Mixed Systems of Liposome and Inorganic Nanoparticle and Their Applications

    Directory of Open Access Journals (Sweden)

    Michael Gradzielski

    2012-09-01

    Full Text Available In the past few years, growing attention has been devoted to the study of the interactions taking place in mixed systems of phospholipid membranes (for instance in the form of vesicles and hard nanoparticles (NPs. In this context liposomes (vesicles may serve as versatile carriers or as a model system for biological membranes. Research on these systems has led to the observation of novel hybrid structures whose morphology strongly depends on the charge, composition and size of the interacting colloidal species as well as on the nature (pH, ionic strength of their dispersing medium. A central role is played by the phase behaviour of phospholipid bilayers which have a tremendous influence on the liposome properties. Another central aspect is the incorporation of nanoparticles into vesicles, which is intimately linked to the conditions required for transporting a nanoparticle through a membrane. Herein, we review recent progress made on the investigations of the interactions in liposome/nanoparticle systems focusing on the particularly interesting structures that are formed in these hybrid systems as well as their potential applications.

  17. Mucosal delivery of liposome-chitosan nanoparticles complexes

    OpenAIRE

    Carvalho, Edison Samir Mascarelhas; Grenha, Ana; Remuñán-López, Carmen; Alonso, Maria José; Seijo, Begoña

    2009-01-01

    Designing adequate drug carriers has long been a major challenge for those working in drug delivery. Since drug delivery strategies have evolved for mucosal delivery as the outstanding alternative to parenteral administration, many new drug delivery systems have been developed which evidence promising properties to address specific issues. Colloidal carriers, such as nanoparticles and liposomes, have been referred to as the most valuable approaches, but still have some limitations that can...

  18. A novel liposome-based nanocarrier loaded with an LPS-dsRNA cocktail for fish innate immune system stimulation.

    Directory of Open Access Journals (Sweden)

    Angels Ruyra

    Full Text Available Development of novel systems of vaccine delivery is a growing demand of the aquaculture industry. Nano- and micro- encapsulation systems are promising tools to achieve efficient vaccines against orphan vaccine fish diseases. In this context, the use of liposomal based-nanocarriers has been poorly explored in fish; although liposomal nanocarriers have successfully been used in other species. Here, we report a new ∼125 nm-in-diameter unilamellar liposome-encapsulated immunostimulant cocktail containing crude lipopolysaccharide (LPS from E. coli and polyinosinic:polycytidylic acid [poly (I:C], a synthetic analog of dsRNA virus, aiming to be used as a non-specific vaccine nanocarrier in different fish species. This liposomal carrier showed high encapsulation efficiencies and low toxicity not only in vitro using three different cellular models but also in vivo using zebrafish embryos and larvae. We showed that such liposomal LPS-dsRNA cocktail is able to enter into contact with zebrafish hepatocytes (ZFL cell line and trout macrophage plasma membranes, being preferentially internalized through caveolae-dependent endocytosis, although clathrin-mediated endocytosis in ZFL cells and macropinocytocis in macrophages also contribute to liposome uptake. Importantly, we also demonstrated that this liposomal LPS-dsRNA cocktail elicits a specific pro-inflammatory and anti-viral response in both zebrafish hepatocytes and trout macrophages. The design of a unique delivery system with the ability to stimulate two potent innate immunity pathways virtually present in all fish species represents a completely new approach in fish health.

  19. Pros and cons of the liposome platform in cancer drug targeting.

    Science.gov (United States)

    Gabizon, Alberto A; Shmeeda, Hilary; Zalipsky, Samuel

    2006-01-01

    Coating of liposomes with polyethylene-glycol (PEG) by incorporation in the liposome bilayer of PEG-derivatized lipids results in inhibition of liposome uptake by the reticulo-endothelial system and significant prolongation of liposome residence time in the blood stream. Parallel developments in drug loading technology have improved the efficiency and stability of drug entrapment in liposomes, particularly with regard to cationic amphiphiles such as anthracyclines. An example of this new generation of liposomes is a formulation of pegylated liposomal doxorubicin known as Doxil or Caelyx, whose clinical pharmacokinetic profile is characterized by slow plasma clearance and small volume of distribution. A hallmark of these long-circulating liposomal drug carriers is their enhanced accumulation in tumors. The mechanism underlying this passive targeting effect is the phenomenon known as enhanced permeability and retention (EPR) which has been described in a broad variety of experimental tumor types. Further to the passive targeting effect, the liposome drug delivery platform offers the possibility of grafting tumor-specific ligands on the liposome membrane for active targeting to tumor cells, and potentially intracellular drug delivery. The pros and cons of the liposome platform in cancer targeting are discussed vis-à-vis nontargeted drugs, using as an example a liposome drug delivery system targeted to the folate receptor.

  20. Recent Trends of Polymer Mediated Liposomal Gene Delivery System

    Directory of Open Access Journals (Sweden)

    Shyamal Kumar Kundu

    2014-01-01

    Full Text Available Advancement in the gene delivery system have resulted in clinical successes in gene therapy for patients with several genetic diseases, such as immunodeficiency diseases, X-linked adrenoleukodystrophy (X-ALD blindness, thalassemia, and many more. Among various delivery systems, liposomal mediated gene delivery route is offering great promises for gene therapy. This review is an attempt to depict a portrait about the polymer based liposomal gene delivery systems and their future applications. Herein, we have discussed in detail the characteristics of liposome, importance of polymer for liposome formulation, gene delivery, and future direction of liposome based gene delivery as a whole.

  1. Entrapment of ovalbumin into liposomes--factors affecting entrapment efficiency, liposome size, and zeta potential.

    Science.gov (United States)

    Brgles, Marija; Jurasin, Darija; Sikirić, Maja Dutour; Frkanec, Ruza; Tomasić, Jelka

    2008-01-01

    Various amounts of Ovalbumin (OVA) were encapsulated into positively and negatively charged multilamellar liposomes, with the aim to investigate the entrapment efficiency in different buffers and to study their effects on the liposome size and zeta potential. Results showed that the entrapment efficiency of OVA in anionic liposomes was the same in 10 mM Phosphate Buffer (PB) as in Phosphate-Buffered Saline (PBS; PB + 0.15 M NaCl). Also, liposome size was approximately 1200 nm for all anionic liposomes incorporating OVA. The entrapment efficiency of OVA in cationic liposomes was highly dependent on ionic strength. The size of cationic liposomes was approximately 1200 nm in PBS, regardless of protein content, but increased with the amount of the incorporated protein in PB. Aggregation of cationic liposomes in PB was observed when the mass of the protein was 2.5 mg or greater. The zeta potential of anionic liposomes was negative and of cationic liposomes positive in the whole range of protein mass tested. These results show how different compositions of lipid and aqueous phases can be used to vary the entrapment efficiency, liposome size, and zeta potential--the factors that are of great importance for the use of liposomes as drug carriers.

  2. Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries

    Directory of Open Access Journals (Sweden)

    Jain PP

    2014-07-01

    Full Text Available Pritesh P Jain,1 Regina Leber,1,2 Chandran Nagaraj,1 Gerd Leitinger,3 Bernhard Lehofer,4 Horst Olschewski,1,5 Andrea Olschewski,1,6 Ruth Prassl,1,4 Leigh M Marsh11Ludwig Boltzmann Institute for Lung Vascular Research, 2Biophysics Division, Institute of Molecular Biosciences, University of Graz, 3Research Unit Electron Microscopic Techniques, Institute of Cell Biology, Histology, and Embryology, 4Institute of Biophysics, 5Division of Pulmonology, Department of Internal Medicine, 6Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, AustriaAbstract: Prostacyclin analogues are standard therapeutic options for vasoconstrictive diseases, including pulmonary hypertension and Raynaud’s phenomenon. Although effective, these treatment strategies are expensive and have several side effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier systems. In this study, we synthesized liposomal nanoparticles tailored for the prostacyclin analogue iloprost and evaluated their pharmacologic efficacy on mouse intrapulmonary arteries, using a wire myograph. The use of cationic lipids, stearylamine, or 1,2-di-(9Z-octadecenoyl-3-trimethylammonium-propane (DOTAP in liposomes promoted iloprost encapsulation to at least 50%. The addition of cholesterol modestly reduced iloprost encapsulation. The liposomal nanoparticle formulations were tested for toxicity and pharmacologic efficacy in vivo and ex vivo, respectively. The liposomes did not affect the viability of human pulmonary artery smooth muscle cells. Compared with an equivalent concentration of free iloprost, four out of the six polymer-coated liposomal formulations exhibited significantly enhanced vasodilation of mouse pulmonary arteries. Iloprost that was encapsulated in liposomes containing the polymer polyethylene glycol exhibited concentration-dependent relaxation of arteries. Strikingly, half the concentration of iloprost in liposomes elicited

  3. Stimuli-responsive Smart Liposomes in Cancer Targeting.

    Science.gov (United States)

    Jain, Ankit; Jain, Sanjay K

    2018-02-08

    Liposomes are vesicular carriers which possess aqueous core entrapped within the lipid bilayer. These are carriers of choice because of biocompatible and biodegradable features in addition to flexibility of surface modifications at surface and lipid compositions of lipid bilayers. Liposomes have been reported well for cancer treatment using both passive and active targeting approaches however tumor microenvironment is still the biggest hurdle for safe and effective delivery of anticancer agents. To overcome this problem, stimuli-responsive smart liposomes have emerged as promising cargoes pioneered to anomalous tumor milieu in response to pH, temperature, and enzymes etc. as internal triggers, and magnetic field, ultrasound, and redox potential as external guides for enhancement of drug delivery to tumors. This review focuses on all such stimuli-responsive approaches using fabrication potentiality of liposomes in combination to various ligands, linkers, and PEGylation etc. Scientists engaged in cancer targeting approaches can get benefited greatly with this knowledgeable assemblage of advances in liposomal nanovectors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Liposomes as carriers of the beta-emitters rhenium-186 and rhenium-188 for use in radiotherapy

    International Nuclear Information System (INIS)

    Haefeli, U.

    1989-01-01

    The two radioisotopes Re-186 and Re-188 are highly favoured as therapeutic nuclides in nuclear medicine due to their unique radiation characteristics. For application in future (e.g. radiosynoviorthesis of the knee) we have chosen liposomes as biodegradable and non-irriting carriers. They were filled with radioactive Re in therapeutic doses of >370 MBq (10 mCi). 1. Small unilamellar liposomes (SUV's) of an average size of 28 nm were prepared by ultrasonic irradiation. They encapsulated only 0.64% of the perrhenate. 2. Liposomes carrying DTPA-SA in their bilayer (SA=octadecylamine) were produced in order to form a complex with Tc and Re. Technetium was complexed in high yield and the Tc-DTPA-liposome bindings were found to be stable when tested by dialysis. Similar attempts to complex Re were not successful because the amount of Sn(+II) required for the reduction was so high that the liposomes were destroyed. 3. Methylthiosemicarbazide (mts) was coupled covalently to aminomethylpolystyrene. These spheres were used as a very convenient and simple model for testing the labelling-yield and the stability of the Re-mts-complex. 4. Two isomers of the complex ReO(OEt)Cl 2 (PPh 3 ) 2 (Rephos) were characterized. These highly lipid-soluble inactive complexes were irradiated by neutrons and then used to prepare a mixed micelle with egg yolk lecithin and the detergent sodium deoxycholate. Liposomes were produced in a size of 60-80 nm in a very simple way by gelfiltration. Up to 53.5% of the radioactive Rephos was incorporated. Monitoring the stability by dialysis an initial loss of 10-15% and subsequent linear decrease were observed. The daily loss could be reduced to 1.0% by the addition of ascorbic acid. After 8 days, 82% of the initial activity still remained in the vesicles. 5. [ReO 2 (en) 2 ]Cl.2H 2 O and [ReO 2 (1,4,8,11-tetraazaundecane)]Cl were synthesized and characterized. 6. A direct enzymatic method to determine the remaining cholate in liposomes was developed

  5. Evaluation of iron transport from ferrous glycinate liposomes using ...

    African Journals Online (AJOL)

    Background: Iron fortification of foods is currently a strategy employed to fight iron deficiency in countries. Liposomes were assumed to be a potential carrier of iron supplements. Objective: The objective of this study was to investigate the iron transport from ferrous glycinate liposomes, and to estimate the effects of liposomal ...

  6. Physicochemical interactions among α-eleostearic acid-loaded liposomes applied to the development of drug delivery systems

    Science.gov (United States)

    Nogueira, Alessandro Oliveira de Moraes; de Sousa, Robson Simplício; Pereira, Luiza Silveira; Mallmann, Christian; da Silva Ferreira, Ailton; Clementin, Rosilene Maria; de Lima, Vânia Rodrigues

    2018-02-01

    In this study, α-eleostearic acid-loaded (α-ESA-loaded) dimyristoylphosphatidylcholine (DMPC) liposomes had their physicochemical properties characterized by horizontal attenuated total reflectance Fourier transform infrared (HATR-FTIR) spectroscopy, nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC). In vitro thiobarbituric acid reactive substance (TBARS) assays were performed to obtain preliminary information on the oxidative potential of the system. An α-ESA-promoted ordering effect in the lipid phosphate region was observed. It was associated with a rotation restriction due to an increase in the amount of lipid group hydrogen bonds. The fatty acid was responsible for the reduction in the degree of hydration of carbonyl groups located in the interfacial region of lipids. α-ESA disordered the DMPC methylene acyl chains by trans-gauche isomerization and increased its rotation rate. TBARS results showed pro-oxidant behavior on liposomes, induced by α-ESA. The discussion about the responses considered the degree of saturation of phosphatidylcholines and suggested that the α-ESA oxidative effects may be modulated by the liposome lipid composition. The versatility of liposomal carriers may be promising for the development of efficacious α-ESA-based drug delivery systems. Results described in this study contribute to the selection of adequate material to produce them.

  7. Pharmacokinetics of a 5-fluorouracil liposomal delivery system.

    OpenAIRE

    Simmons, S T; Sherwood, M B; Nichols, D A; Penne, R B; Sery, T; Spaeth, G L

    1988-01-01

    A liposomal delivery system was developed in an attempt to prolong ocular levels of 5-fluorouracil for glaucoma filtering surgery. The pharmacokinetics of the 5-fluorouracil liposomal delivery system were studied in normal pigmented rabbits with 5-fluorouracil labelled with carbon-14 (C-14). 14C 5-fluorouracil was incorporated into the liposomes at a concentration of 10 g/l and injected subconjunctivally in doses of 5 and 10 mg. Concentrations of 5-fluorouracil were assayed at 10 time interva...

  8. trans-Double Bond-Containing Liposomes as Potential Carriers for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Giorgia Giacometti

    2017-11-01

    Full Text Available The use of liposomes has been crucial for investigations in biomimetic chemical biology as a membrane model and in medicinal chemistry for drug delivery. Liposomes are made of phospholipids whose biophysical characteristics strongly depend on the type of fatty acid moiety, where natural unsaturated lipids always have the double bond geometry in the cis configuration. The influence of lipid double bond configuration had not been considered so far with respect to the competence of liposomes in delivery. We were interested in evaluating possible changes in the molecular properties induced by the conversion of the double bond from cis to trans geometry. Here we report on the effects of the addition of trans-phospholipids supplied in different amounts to other liposome constituents (cholesterol, neutral phospholipids and cationic surfactants, on the size, ζ-potential and stability of liposomal formulations and on their ability to encapsulate two dyes such as rhodamine B and fluorescein. From a biotechnological point of view, trans-containing liposomes proved to have different characteristics from those containing the cis analogues, and to influence the incorporation and release of the dyes. These results open new perspectives in the use of the unnatural lipid geometry, for the purpose of changing liposome behavior and/or of obtaining molecular interferences, also in view of synergic effects of cell toxicity, especially in antitumoral strategies.

  9. Partially polymerized liposomes: stable against leakage yet capable of instantaneous release for remote controlled drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Qin Guoting; Li Zheng; Xia Rongmin; Li Feng; O' Neill, Brian E; Li, King C [Department of Radiology, The Methodist Hospital Research Institute, Houston, TX 77030 (United States); Goodwin, Jessica T; Khant, Htet A; Chiu, Wah, E-mail: zli@tmhs.org, E-mail: kli@tmhs.org [National Center for Macromolecular Imaging, Baylor College of Medicine, Houston, TX 77030 (United States)

    2011-04-15

    A critical issue for current liposomal carriers in clinical applications is their leakage of the encapsulated drugs that are cytotoxic to non-target tissues. We have developed partially polymerized liposomes composed of polydiacetylene lipids and saturated lipids. Cross-linking of the diacetylene lipids prevents the drug leakage even at 40 deg. C for days. These inactivated drug carriers are non-cytotoxic. Significantly, more than 70% of the encapsulated drug can be instantaneously released by a laser that matches the plasmon resonance of the tethered gold nanoparticles on the liposomes, and the therapeutic effect was observed in cancer cells. The remote activation feature of this novel drug delivery system allows for precise temporal and spatial control of drug release.

  10. Superresolution and Fluorescence Dynamics Evidence Reveal That Intact Liposomes Do Not Cross the Human Skin Barrier

    DEFF Research Database (Denmark)

    Dreier, Jes; Sørensen, Jens A; Brewer, Jonathan R

    2016-01-01

    In this study we use the combination of super resolution optical microscopy and raster image correlation spectroscopy (RICS) to study the mechanism of action of liposomes as transdermal drug delivery systems in human skin. Two different compositions of liposomes were applied to newly excised human...... skin, a POPC liposome and a more flexible liposome containing the surfactant sodium cholate. Stimulated emission depletion microscopy (STED) images of intact skin and cryo-sections of skin treated with labeled liposomes were recorded displaying an optical resolution low enough to resolve the 100 nm...... liposomes in the skin. The images revealed that virtually none of the liposomes remained intact beneath the skin surface. RICS two color cross correlation diffusion measurements of double labeled liposomes confirmed these observations. Our results suggest that the liposomes do not act as carriers...

  11. Plasmon resonant liposomes for controlled drug delivery

    Science.gov (United States)

    Knights-Mitchell, Shellie S.; Romanowski, Marek

    2015-03-01

    Nanotechnology use in drug delivery promotes a reduction in systemic toxicity, improved pharmacokinetics, and better drug bioavailability. Liposomes continue to be extensively researched as drug delivery systems (DDS) with formulations such as Doxil® and Ambisome® approved by FDA and successfully marketed in the United States. However, the limited ability to precisely control release of active ingredients from these vesicles continues to challenge the broad implementation of this technology. Moreover, the full potential of the carrier to sequester drugs until it can reach its intended target has yet to be realized. Here, we describe a liposomal DDS that releases therapeutic doses of an anticancer drug in response to external stimulus. Earlier, we introduced degradable plasmon resonant liposomes. These constructs, obtained by reducing gold on the liposome surface, facilitate spatial and temporal release of drugs upon laser light illumination that ultimately induces an increase in temperature. In this work, plasmon resonant liposomes have been developed to stably encapsulate and retain doxorubicin at physiological conditions represented by isotonic saline at 37o C and pH 7.4. Subsequently, they are stimulated to release contents either by a 5o C increase in temperature or by laser illumination (760 nm and 88 mW/cm2 power density). Successful development of degradable plasmon resonant liposomes responsive to near-infrared light or moderate hyperthermia can provide a new delivery method for multiple lipophilic and hydrophilic drugs with pharmacokinetic profiles that limit clinical utility.

  12. Silica-coated flexible liposomes as a nanohybrid delivery system for enhanced oral bioavailability of curcumin

    Directory of Open Access Journals (Sweden)

    Li C

    2012-12-01

    Full Text Available Chong Li, Yan Zhang, Tingting Su, Lianlian Feng, Yingying Long, Zhangbao ChenKey Laboratory on Luminescence and Real-Time Analysis, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, ChinaAbstract: We investigated flexible liposomes as a potential oral drug delivery system. However, enhanced membrane fluidity and structural deformability may necessitate liposomal surface modification when facing the harsh environment of the gastrointestinal tract. In the present study, silica-coated flexible liposomes loaded with curcumin (CUR-SLs having poor water solubility as a model drug were prepared by a thin-film method with homogenization, followed by the formation of a silica shell by the sol-gel process. We systematically investigated the physical properties, drug release behavior, pharmacodynamics, and bioavailability of CUR-SLs. CUR-SLs had a mean diameter of 157 nm and a polydispersity index of 0.14, while the apparent entrapment efficiency was 90.62%. Compared with curcumin-loaded flexible liposomes (CUR-FLs without silica-coatings, CUR-SLs had significantly higher stability against artificial gastric fluid and showed more sustained drug release in artificial intestinal fluid as determined by in vitro release assays. The bioavailability of CUR-SLs and CUR-FLs was 7.76- and 2.35-fold higher, respectively, than that of curcumin suspensions. Silica coating markedly improved the stability of flexible liposomes, and CUR-SLs exhibited a 3.31-fold increase in bioavailability compared with CUR-FLs, indicating that silica-coated flexible liposomes may be employed as a potential carrier to deliver drugs with poor water solubility via the oral route with improved bioavailability.Keywords: silica, flexible liposome, oral bioavailability, curcumin

  13. Pharmacokinetics of a 5-fluorouracil liposomal delivery system.

    Science.gov (United States)

    Simmons, S T; Sherwood, M B; Nichols, D A; Penne, R B; Sery, T; Spaeth, G L

    1988-01-01

    A liposomal delivery system was developed in an attempt to prolong ocular levels of 5-fluorouracil for glaucoma filtering surgery. The pharmacokinetics of the 5-fluorouracil liposomal delivery system were studied in normal pigmented rabbits with 5-fluorouracil labelled with carbon-14 (C-14). 14C 5-fluorouracil was incorporated into the liposomes at a concentration of 10 g/l and injected subconjunctivally in doses of 5 and 10 mg. Concentrations of 5-fluorouracil were assayed at 10 time intervals from 0.5 to 96 hours in cornea, sclera, and conjunctiva and at six time intervals from 0.5 to 12 hours in aqueous. Two peak concentrations were noted at approximately one and eight hours, with measurable levels present at 96 hours. This study demonstrates the ability of this liposomal delivery system to prolong levels of 5-fluorouracial in normal pigmented rabbits. PMID:3179257

  14. Formulation and Evaluation of Rifampicin Liposomes for Buccal Drug Delivery.

    Science.gov (United States)

    Lankalapalli, Srinivas; Tenneti, V S Vinai Kumar

    2016-01-01

    Drug delivery through liposomes offers several advantages, but still challenging to the researchers for the use of liposomes as carriers in drug delivery due to their poor physical stability, unpredictable drug encapsulation and systemic availability of the loaded drug. The present investigation was planned with an objective to prepare Rifampicin loaded liposomes by using response surface methodology of statistical 32 factorial design and further to formulate them into pastilles for deliver through buccal route thereby to enhance systemic absorption. Rifampicin liposomes were prepared by using different ratios of soya lecithin and cholesterol by solvent Injection method. These liposomes were characterized by using optical microscopy, Scanning Electron Microscopy (SEM) and evaluated for particle size, entrapment efficiency (EE), in vitro and ex vivo drug release. Main effects and interaction terms of the formulation variables were evaluated quantitatively using a mathematical statistical model approach showing that both independent variables have significant (P value value: 0.0273), percentage entrapment efficiency (P value: 0.0096), percentage drug release through dialysis membrane (P value: 0.0047) and percentage drug release through porcine buccal membrane (P value: 0.0019). The statistical factorial design of liposomal formulations fulfilled all the requirements of the target set and exhibited suitable values for the selected test parameters. Pastilles were prepared for liposomes using glycerol gelatin base and were found to be soft, smooth with uniform drug content and drug release.

  15. Comparison of conventional chemotherapy, stealth liposomes and temperature-sensitive liposomes in a mathematical model.

    Directory of Open Access Journals (Sweden)

    Astrid Gasselhuber

    Full Text Available Various liposomal drug carriers have been developed to overcome short plasma half-life and toxicity related side effects of chemotherapeutic agents. We developed a mathematical model to compare different liposome formulations of doxorubicin (DOX: conventional chemotherapy (Free-DOX, Stealth liposomes (Stealth-DOX, temperature sensitive liposomes (TSL with intra-vascular triggered release (TSL-i, and TSL with extra-vascular triggered release (TSL-e. All formulations were administered as bolus at a dose of 9 mg/kg. For TSL, we assumed locally triggered release due to hyperthermia for 30 min. Drug concentrations were determined in systemic plasma, aggregate body tissue, cardiac tissue, tumor plasma, tumor interstitial space, and tumor cells. All compartments were assumed perfectly mixed, and represented by ordinary differential equations. Contribution of liposomal extravasation was negligible in the case of TSL-i, but was the major delivery mechanism for Stealth-DOX and for TSL-e. The dominant delivery mechanism for TSL-i was release within the tumor plasma compartment with subsequent tissue- and cell uptake of released DOX. Maximum intracellular tumor drug concentrations for Free-DOX, Stealth-DOX, TSL-i, and TSL-e were 3.4, 0.4, 100.6, and 15.9 µg/g, respectively. TSL-i and TSL-e allowed for high local tumor drug concentrations with reduced systemic exposure compared to Free-DOX. While Stealth-DOX resulted in high tumor tissue concentrations compared to Free-DOX, only a small fraction was bioavailable, resulting in little cellular uptake. Consistent with clinical data, Stealth-DOX resulted in similar tumor intracellular concentrations as Free-DOX, but with reduced systemic exposure. Optimal release time constants for maximum cellular uptake for Stealth-DOX, TSL-e, and TSL-i were 45 min, 11 min, and <3 s, respectively. Optimal release time constants were shorter for MDR cells, with ∼4 min for Stealth-DOX and for TSL-e. Tissue concentrations

  16. Characterization data on the topical carrier DDC642

    Directory of Open Access Journals (Sweden)

    Eline Desmet

    2016-06-01

    Full Text Available This article contains original data, figures and methods used in the characterization of the liposomal carrier ‘DDC642’ for topical applications, described in “An elastic liposomal formulation for RNAi-based topical treatment of skin disorders: proof-of-concept in the treatment of psoriasis” (Desmet et al., 2016 [1]. Several elastic liposomal formulations have been evaluated for their ability to encapsulate and deliver RNA interference (RNAi molecules to cultured primary skin cells. The efficiency and effectiveness of these liposomes were compared to that of our previously characterized liposomes, the ‘SECosomes’ (SEC (Geusens et al., 2010 [2]. After selection of a potential superior carrier, based on encapsulation and transfection efficiency data (Desmet et al., 2016 [1], the selected DDC642 liposomes were characterized more in-depth. Herein, a detailed characterization of the DDC642 liposome and RNAi-loaded lipoplexes is given, including the matching protocols.

  17. Ultradeformable Liposomes: a Novel Vesicular Carrier For Enhanced Transdermal Delivery of Procyanidins: Effect of Surfactants on the Formation, Stability, and Transdermal Delivery.

    Science.gov (United States)

    Chen, Rencai; Li, Rongli; Liu, Qian; Bai, Chao; Qin, Benlin; Ma, Yue; Han, Jing

    2017-07-01

    The aims of this work were to develop a novel vesicular carrier, procyanidins, ultradeformable liposomes (PUDLs), to expand the applications for procyanidins, and increase their stability and transdermal delivery. In this study, we prepared procyanidins ultradeformable liposomes using thin film hydration method and evaluated their encapsulation efficiency, vesicle deformability, storage stability, and skin permeation in vitro. The influence of different surfactants on the properties of PUDLs was also investigated. The results obtained showed that the PUDLs containing Tween 80 had a high entrapment efficiency (80.27 ± 0.99%), a small particle size (140.6 ± 19 nm), high elasticity, and prolonged drug release. Compared with procyanidins solution, the stability of procyanidins in PUDLs improved significantly when stored at 4, 25, and 30°C. The penetration rate of PUDLs was 6.25-fold greater than that of procyanidins solution. Finally, the results of our study suggested that PUDLs could increase the transdermal flux, prolong the release and improve the stability of procyanidins, and could serve as an effective dermal delivery system for procyanidins.

  18. Fluorescent cell-traceable dexamethasone-loaded liposomes for the treatment of inflammatory liver diseases

    NARCIS (Netherlands)

    Bartneck, M.; Scheyda, K.M.; Warzecha, K.T.; Rizzo, L.Y.; Hittatiya, K.; Luedde, T.; Storm, Gerrit; Trautwein, C.; Lammers, Twan Gerardus Gertudis Maria; Tacke, F.

    2015-01-01

    Liposomes are routinely used carrier materials for delivering drug molecules to pathological sites. Besides in tumors and inflammatory sites, liposomes also strongly accumulate in liver and spleen. The potential of using liposomes to treat acute and chronic liver disorders, however, has not yet been

  19. Fluorescent cell-traceable dexamethasone-loaded liposomes for the treatment of inflammatory liver diseases

    NARCIS (Netherlands)

    Bartneck, Matthias; Scheyda, Katharina M; Warzecha, Klaudia T; Rizzo, Larissa Y; Hittatiya, Kanishka; Luedde, Tom; Storm, G; Trautwein, Christian; Lammers, Twan; Tacke, Frank

    Liposomes are routinely used carrier materials for delivering drug molecules to pathological sites. Besides in tumors and inflammatory sites, liposomes also strongly accumulate in liver and spleen. The potential of using liposomes to treat acute and chronic liver disorders, however, has not yet been

  20. Liposomal preparations of muramyl glycopeptides as immunomodulators and adjuvants.

    Science.gov (United States)

    Turánek, Jaroslav; Ledvina, Miroslav; Kasná, Andrea; Vacek, Antonín; Hríbalova, Vera; Krejcí, Josef; Miller, Andrew D

    2006-04-12

    The need for safe and structurally defined immunomodulators and adjuvants is increasing in connection with the recently observed marked increase in the prevalence of pathological conditions characterized by immunodeficiency. Important groups of such compounds are muramyl glycopeptides, analogs of muramyl dipeptide (MDP), glucosaminyl-muramyl dipeptide (GMDP), and desmuramylpeptides. We have designed and synthesized new types of analogs with changes in both the sugar and the peptide parts of the molecule that show a high immunostimulating and adjuvant activity and suppressed adverse side effects. The introduction of lipophilic residues has also improved their incorporation into liposomes, which represent a suitable drug carrier. The proliposome-liposome method is based on the conversion of the initial proliposome preparation into liposome dispersion by dilution with the aqueous phase. The description of a home-made stirred thermostated cell and its link-up with a liquid delivery system for a rapid and automated preparation of multilamellar liposomes at strictly controlled conditions (sterility, temperature, dilution rate and schedule) is presented. The cell has been designed for laboratory-scale preparation of liposomes (300-1000 mg of phospholipid per run) in a procedure taking less than 90 min. The method can be readily scaled up. Examples of adjuvant and immunostimulatory effect of liposomal preparation in mice model will be presented.

  1. Histidine-lysine peptides as carriers of nucleic acids.

    Science.gov (United States)

    Leng, Qixin; Goldgeier, Lisa; Zhu, Jingsong; Cambell, Patricia; Ambulos, Nicholas; Mixson, A James

    2007-03-01

    With their biodegradability and diversity of permutations, peptides have significant potential as carriers of nucleic acids. This review will focus on the sequence and branching patterns of peptide carriers composed primarily of histidines and lysines. While lysines within peptides are important for binding to the negatively charged phosphates, histidines are critical for endosomal lysis enabling nucleic acids to reach the cytosol. Histidine-lysine (HK) polymers by either covalent or ionic bonds with liposomes augment transfection compared to liposome carriers alone. More recently, we have examined peptides as sole carriers of nucleic acids because of their intrinsic advantages compared to the bipartite HK/liposome carriers. With a protocol change and addition of a histidine-rich tail, HK peptides as sole carriers were more effective than liposomes alone in several cell lines. While four-branched polymers with a primary repeating sequence pattern of -HHK- were more effective as carriers of plasmids, eight-branched polymers with a sequence pattern of -HHHK- were more effective as carriers of siRNA. Compared to polyethylenimine, HK carriers of siRNA and plasmids had reduced toxicity. When injected intravenously, HK polymers in complex with plasmids encoding antiangiogenic proteins significantly decreased tumor growth. Furthermore, modification of HK polymers with polyethylene glycol and vascular-specific ligands increased specificity of the polyplex to the tumor by more than 40-fold. Together with further development and insight on the structure of HK polyplexes, HK peptides may prove to be useful as carriers of different forms of nucleic acids both in vitro and in vivo.

  2. Internal radiotherapy and dosimetric study for 111In/177Lu-pegylated liposomes conjugates in tumor-bearing mice

    International Nuclear Information System (INIS)

    Wang, H.-E.; Yu, H.-M.; Lu, Y.-C.; Heish, N.-N.; Tseng, Yun-Long; Huang, K.-L.; Chuang, K.-T.; Chen, Chin-Hsiung; Hwang, J.-J.; Lin, W.-J.; Wang, Shyh-Jen; Ting, G.; Whang-Peng, Jacqueline; Deng, W.-P.

    2006-01-01

    In vivo characterization and dosimetric analysis has been performed to evaluate the potential of pegylated liposomes as carriers of radionuclides in tumor internal radiotherapy. Methods: The DTPA/PEG-liposomes were synthesized with a medium size of 110 nm, conjugated with 111 In/ 177 Lu-(oxine) 3 to afford 111 In/ 177 Lu-liposome. The stability of 111 In/ 177 Lu-liposome in serum was investigated. The biodistribution, scintigraphic imaging and pharmacokinetics of 111 In/ 177 Lu-liposomes after intravenous(i.v.) injection into C-26 tumor-bearing BALB/cByJ mice were studied. Radiation dose was estimated by MIRD-III program. Results: The incorporation efficiency of 111 In/ 177 Lu into liposomes was 95%. After incubation at 37 o C for 72 h in serum, more than 83% of radioactivity was still retained in the intact 111 In/ 177 Lu-liposomes. The biodistribution of 111 In-liposomes showed that the radioactivity in the blood decreased from 23.14±8.16%ID/g at 1 h to 0.02±0.00%ID/g at 72 h post-injection (p.i.), while reaching its maximum accumulation in tumors at 48 h p.i., with half-life in blood of 10.2 h. The results were supported by that of 177 Lu-liposomes. Scintigraphic imaging with 111 In-liposomes showed unambiguous tumor images at 48 h p.i. Dose estimation showed that the absorbed dose in tumor from 177 Lu-liposomes was 5.74x10 -5 Gy/MBq. Conclusions: This study provides an in vivo characterization and dosimetric evaluation for the use of liposome systems as carriers in targeted radionuclide therapy. The results suggest that adequate tumor targeting as well as dose delivered to tumors could be achieved by the use of radionuclide targeted liposomes

  3. Liposome-based DNA carriers may induce cellular stress response and change gene expression pattern in transfected cells

    Science.gov (United States)

    2011-01-01

    Background During functional studies on the rat stress-inducible Hspa1b (hsp70.1) gene we noticed that some liposome-based DNA carriers, which are used for transfection, induce its promoter activity. This observation concerned commercial liposome formulations (LA), Lipofectin and Lipofectamine 2000. This work was aimed to understand better the mechanism of this phenomenon and its potential biological and practical consequences. Results We found that a reporter gene driven by Hspa1b promoter is activated both in the case of transient transfections and in the stably transfected cells treated with LA. Using several deletion clones containing different fragments of Hspa1b promoter, we found that the regulatory elements responsible for most efficient LA-driven inducibility were located between nucleotides -269 and +85, relative to the transcription start site. Further studies showed that the induction mechanism was independent of the classical HSE-HSF interaction that is responsible for gene activation during heat stress. Using DNA microarrays we also detected significant activation of the endogenous Hspa1b gene in cells treated with Lipofectamine 2000. Several other stress genes were also induced, along with numerous genes involved in cellular metabolism, cell cycle control and pro-apoptotic pathways. Conclusions Our observations suggest that i) some cationic liposomes may not be suitable for functional studies on hsp promoters, ii) lipofection may cause unintended changes in global gene expression in the transfected cells. PMID:21663599

  4. Liposome-based DNA carriers may induce cellular stress response and change gene expression pattern in transfected cells

    Directory of Open Access Journals (Sweden)

    Lisowska Katarzyna Marta

    2011-06-01

    Full Text Available Abstract Background During functional studies on the rat stress-inducible Hspa1b (hsp70.1 gene we noticed that some liposome-based DNA carriers, which are used for transfection, induce its promoter activity. This observation concerned commercial liposome formulations (LA, Lipofectin and Lipofectamine 2000. This work was aimed to understand better the mechanism of this phenomenon and its potential biological and practical consequences. Results We found that a reporter gene driven by Hspa1b promoter is activated both in the case of transient transfections and in the stably transfected cells treated with LA. Using several deletion clones containing different fragments of Hspa1b promoter, we found that the regulatory elements responsible for most efficient LA-driven inducibility were located between nucleotides -269 and +85, relative to the transcription start site. Further studies showed that the induction mechanism was independent of the classical HSE-HSF interaction that is responsible for gene activation during heat stress. Using DNA microarrays we also detected significant activation of the endogenous Hspa1b gene in cells treated with Lipofectamine 2000. Several other stress genes were also induced, along with numerous genes involved in cellular metabolism, cell cycle control and pro-apoptotic pathways. Conclusions Our observations suggest that i some cationic liposomes may not be suitable for functional studies on hsp promoters, ii lipofection may cause unintended changes in global gene expression in the transfected cells.

  5. [Advances in novel carrier systems of chemical constituents from spice volatile oils].

    Science.gov (United States)

    Zhang, Jia-jia; Zhu, Yuan; Yu, Jiang-nan; Xu, Xi-ming

    2015-10-01

    Recent years, chemical constituents from spice volatile oils have gained worldwide concern owing to its multiple pharmacological effects and safety for using as the natural antibacterial agents. However, their poor dissolution, strong volatility, serious irritation, weak stability, easy oxidation and low bioavailability characteristics are the major obstacle in the preparation of effective oral formulation and practical application. Therefore, there is an urgent need to select a novel carrier system that can delivery the chemical constituents from spice volatile oils more efficiently with improving their stability as well as alleviating the irritation, and develop the functional food, health products and even medicine for exerting their pharmacological effects, which also is the focus and nodus of the research on their application. This review presents recent systematic studies on their novel carrier systems, including cyclodextrin inclusion complex, liposomes, nanoemulsions, nanoparticles, solid dispersion and so on, and summarizes the characteristics, application range and problems of each novel carrier systems, in order to provide some beneficial thoughts in further developing new products of chemical constituents from spice volatile oils.

  6. G5 PAMAM dendrimer versus liposome: a comparison study on the in vitro transepithelial transport and in vivo oral absorption of simvastatin.

    Science.gov (United States)

    Qi, Rong; Zhang, Heran; Xu, Lu; Shen, Wenwen; Chen, Cong; Wang, Chao; Cao, Yini; Wang, Yunan; van Dongen, Mallory A; He, Bing; Wang, Siling; Liu, George; Banaszak Holl, Mark M; Zhang, Qiang

    2015-07-01

    This study compared formulation effects of a dendrimer and a liposome preparation on the water solubility, transepithelial transport, and oral bioavailability of simvastatin (SMV). Amine-terminated G5 PAMAM dendrimer (G5-NH2) was chosen to form SMV/G5-NH2 molecular complexes, and SMV-liposomes were prepared by using a thin film dispersion method. The effects of these preparations on the transepithelial transport were investigated in vitro using Caco-2 cell monolayers. Results indicated that the solubility and transepithelial transport of SMV were significantly improved by both formulations. Pharmacokinetic studies in rats also revealed that both the SMV/G5-NH2 molecular complexes and the SMV-liposomes significantly improved the oral bioavailability of SMV with the liposomes being more effective than the G5-NH2. The overall better oral absorption of SMV-liposomes as compared to SMV/G5-NH2 molecular complexes appeared to arise from better liposomal solubilization and encapsulation of SMV and more efficient intracellular SMV delivery. Various carrier systems have been designed to enhance drug delivery via the oral route. In this study, the authors compared G5 PAMAM dendrimers to liposome preparations in terms of solubility, transepithelial transport, and oral bioavailability of this poorly water-soluble drug. This understanding has improved our knowledge in the further development of drug carrier systems. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Lipossomas: a bala mágica acertou? Liposomes: has the magic bullet hit the target?

    Directory of Open Access Journals (Sweden)

    Nuno C. Santos

    2002-12-01

    Full Text Available Efficient drug delivery systems are as important as drug themselves. A powerful drug unable to reach the target cell is useless in practice. Ehrlich's Magic Bullet was the first carrier system to be proposed. The evolution in this domain has been quite slow as the natural mechanisms of mammals against foreign products are hard to overcome. However, lipid-based systems (liposomes and related vesicles have attained reasonable success. The basic preparations and structural features of liposomes and related vesicles as well as their applications are addressed from the chemist's and biochemist's point of view.

  8. Superresolution and Fluorescence Dynamics Evidence Reveal That Intact Liposomes Do Not Cross the Human Skin Barrier.

    Directory of Open Access Journals (Sweden)

    Jes Dreier

    Full Text Available In this study we use the combination of super resolution optical microscopy and raster image correlation spectroscopy (RICS to study the mechanism of action of liposomes as transdermal drug delivery systems in human skin. Two different compositions of liposomes were applied to newly excised human skin, a POPC liposome and a more flexible liposome containing the surfactant sodium cholate. Stimulated emission depletion microscopy (STED images of intact skin and cryo-sections of skin treated with labeled liposomes were recorded displaying an optical resolution low enough to resolve the 100 nm liposomes in the skin. The images revealed that virtually none of the liposomes remained intact beneath the skin surface. RICS two color cross correlation diffusion measurements of double labeled liposomes confirmed these observations. Our results suggest that the liposomes do not act as carriers that transport their cargo directly through the skin barrier, but mainly burst and fuse with the outer lipid layers of the stratum corneum. It was also found that the flexible liposomes showed a greater delivery of the fluorophore into the stratum corneum, indicating that they functioned as chemical permeability enhancers.

  9. From conventional to stealth liposomes: a new frontier in cancer chemotherapy.

    Science.gov (United States)

    Cattel, Luigi; Ceruti, Maurizio; Dosio, Franco

    2003-01-01

    Many attempts have been made to achieve good selectivity to targeted tumor cells by preparing specialized carrier agents that are therapeutically profitable for anticancer therapy. Among these, liposomes are the most studied colloidal particles thus far applied in medicine and in particular in antitumor therapy. Although they were first described in the 1960s, only at the beginning of 1990s did the first therapeutic liposomes appear on the market. The first-generation liposomes (conventional liposomes) comprised a liposome-containing amphotericin B, Ambisome (Nexstar, Boulder, CO, USA), used as an antifungal drug, and Myocet (Elan Pharma Int, Princeton, NJ, USA), a doxorubicin-containing liposome, used in clinical trials to treat metastatic breast cancer. The second-generation liposomes ("pure lipid approach") were long-circulating liposomes, such as Daunoxome, a daunorubicin-containing liposome approved in the US and Europe to treat AIDS-related Kaposi's sarcoma. The third-generation liposomes were surface-modified liposomes with gangliosides or sialic acid, which can evade the immune system responsible for removing liposomes from circulation. The fourth-generation liposomes, pegylated liposomal doxorubicin, were called "stealth liposomes" because of their ability to evade interception by the immune system, in the same way as the stealth bomber was able to evade radar. Actually, the only stealth liposome on the market is Caelyx/Doxil (Schering-Plough, Madison NJ, USA), used to cure AIDS-related Kaposi's sarcoma, resistant ovarian cancer and metastatic breast cancer. Pegylated liposomal doxorubicin is characterized by a very long-circulation half-life, favorable pharmacokinetic behavior and specific accumulation in tumor tissues. These features account for the much lower toxicity shown by Caelyx in comparison to free doxorubicin, in terms of cardiotoxicity, vesicant effects, nausea, vomiting and alopecia. Pegylated liposomal doxorubicin also appeared to be less

  10. Process Variables and Design of Experiments in Liposome and Nanoliposome Research.

    Science.gov (United States)

    Zoghi, Alaleh; Khosravi-Darani, Kianoush; Omri, Abdelwahab

    2018-01-01

    Liposomes vesicles consisting of one or more phospholipid bilayers are microcarriers used in numerous scientific disciplines. During the last decade, nanostructured liposomes, or nanoliposomes, have been utilized in biomedical investigations due to their unique characteristics including nanoscale size, sustained release, biocompatibility, and biodegradability. The extensive literature covering the field of liposomology is an indication of increasing interests and applications in many areas, especially as carriers of active substances in nanomedicine, agriculture, food technology, and cosmetics. Nanoliposomes application as drug carriers resulted in more effective treatment of such diseases as cancers, atherosclerosis, infectious diseases and ocular disorders. In this communication, we will introduce commonly used methods for the preparation of liposome, pointing the therapeutic report of liposomes, and explaining the common process variables in liposome encapsulations. We will also review different screening methods and full and fractional factorial designs that impact independent variables in certain applications and the end-user response. We will review such key factors as encapsulation efficiency, loading capacity, particles' biologic, structural and physicochemical properties, and lipid composition in an effort to provide a comprehensive guide for liposomologists in different fields of interest. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. AlPcS4-PDT for gastric cancer therapy using gold nanorod, cationic liposome, and Pluronic® F127 nanomicellar drug carriers.

    Science.gov (United States)

    Xin, Jing; Wang, Sijia; Wang, Bing; Wang, Jiazhuang; Wang, Jing; Zhang, Luwei; Xin, Bo; Shen, Lijian; Zhang, Zhenxi; Yao, Cuiping

    2018-01-01

    As a promising photodynamic therapy (PDT) agent, Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS 4 ) provides deep penetration into tissue, high quantum yields, good photostability, and low photobleaching. However, its low delivery efficiency and high binding affinity to serum albumin cause its low penetration into cancer cells, further limiting its PDT effect on gastric cancer. In order to improve AlPcS 4 /PDT effect, the AlPcS 4 delivery sys tems with different drug carriers were synthesized and investigated. Gold nanorods, cationic liposomes, and Pluronic ® F127 nanomicellars were used to formulate the AlPcS 4 delivery systems. The anticancer effect was evaluated by CCK-8 assay and colony formation assay. The delivery efficiency of AlPcS 4 and the binding affinity to serum proteins were determined by fluorescence intensity assay. The apoptosis and necrosis ability, reactive oxygen species and singlet oxygen generation, mitochondrial transmembrane potential and ([Ca 2+ ] i ) concentration were further measured to evaluate the mechanism of cell death. The series of synthesized AlPcS 4 delivery systems with different drug carriers improve the limited PDT effect in varying degrees. In contrast, AlPcS 4 complex with gold nanorods has significant anticancer effects because gold nanorods are not only suitable for AlPcS 4 delivery, but also exhibit enhanced singlet oxygen generation effect and photothermal effect to induce cell death directly. Moreover, AlPcS 4 complex with cationic liposomes shows the potent inhibition effect because of its optimal AlPcS 4 delivery efficiency and ability to block serum albumin. In addition, AlPcS 4 complex with Pluronic F127 exhibits inferior PDT effect but presents lower cytotoxicity, slower dissociation rate, and longer retention time of incorporated drugs; thus, F127-AlPcS 4 is used for prolonged gastric cancer therapy. The described AlPcS 4 drug delivery systems provide promising agents for gastric cancer therapy.

  12. Interaction of dipalmitoyl phosphatidylcholine (DPPC) liposomes and insulin

    Science.gov (United States)

    Mady, Mohsen M.; Elshemey, Wael M.

    2011-06-01

    Insulin, a peptide that has been used for decades in the treatment of diabetes, has well-defined properties and delivery requirements. Liposomes, which are lipid bilayer vesicles, have gained increasing attention as drug carriers which reduce the toxicity and increase the pharmacological activity of various drugs. The molecular interaction between (uncharged lipid) dipalmitoyl phosphatidylcholine (DPPC) liposomes and insulin has been characterized by using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction. The characteristic protein absorption band peaks, Amide I (at about 1660 cm-1) and Amide II band (at about 1546 cm-1) are potentially reduced in the liposome insulin complex. Wide-angle x-ray scattering measurements showed that the association of insulin with DPPC lipid of liposomes still maintains the characteristic DPPC diffraction peaks with almost no change in relative intensities or change in peak positions. The absence of any shift in protein peak positions after insulin being associated with DPPC liposomes indicates that insulin is successfully forming complex with DPPC liposomes with possibly no pronounced alterations in the structure of insulin molecule.

  13. Liposomal Drug Delivery of Anticancer Agents

    DEFF Research Database (Denmark)

    Pedersen, Palle Jacob

    and retention (EPR) effect. The liposomes consists of sPLA2 IIA sensitive phospholipids having anticancer drugs covalently attached to the sn-2 position of the glycerol backbone in the phospholipids, hence drug leakage is avoided from the carrier system. Various known anticancer agents, like chlorambucil, all......) based strategy using a limited number of reaction types. Upon coupling of unsaturated building blocks ring closing metathesis cascades were used to “reprogram” the molecular scaffold and highly diverse structures were obtained. In total 20 novel compounds with a broad structural diversity were prepared...

  14. Transferrin-modified liposome promotes α-mangostin to penetrate the blood-brain barrier.

    Science.gov (United States)

    Chen, Zhi-Lan; Huang, Man; Wang, Xia-Rong; Fu, Jun; Han, Min; Shen, You-Qing; Xia, Zheng; Gao, Jian-Qing

    2016-02-01

    α-Mangostin (α-M) is a polyphenolic xanthone that protects and improves the survival of cerebral cortical neurons against Aβ oligomer-induced toxicity in rats. α-M is a potential candidate as a treatment for Alzheimer's disease (AD). However, the efficacy was limited by the poor penetration of the drug through the blood-brain barrier (BBB). In this study, we modified the α-M liposome with transferrin (Tf) and investigated the intracellular distribution of liposomes in bEnd3 cells. In addition, the transport of α-M across the BBB in the Tf(α-M) liposome group was examined. In vitro studies demonstrated that the Tf(α-M) liposome could cross the BBB in the form of an integrated liposome. Results of the in vivo studies on the α-M distribution in the brain demonstrated that the Tf(α-M) liposome improved the brain delivery of α-M. These results indicated that the Tf liposome is a potential carrier of α-M against AD. The use of α-Mangostin (α-M) as a potential agent to treat Alzheimer's disease (AD) has been reported. However, its use is limited by the poor penetration through the blood brain barrier. The delivery of this agent by transferrin-modified liposomes was investigated by the authors in this study. The positive results could point to a better drug delivery system for brain targeting. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Liposome-Based Delivery Systems in Plant Polysaccharides

    International Nuclear Information System (INIS)

    Meiwan, C.; Yitao, W.; Yanfang, Z.; Xinsheng, P.; Jingjing, H.; Ping, Z.

    2012-01-01

    Plant polysaccharides consist of many monosaccharide by α or β glycosidic bond which can be extracted by the water, alcohol, lipophile liquid from a variety of plants including Cordyceps sinensis, astragalus, and mushrooms. Recently, many evidences illustrate that natural plant polysaccharides possess various biological activities including strengthening immunity, lowering blood sugar, regulating lipid metabolism, anti oxidation, anti aging, and antitumour. Plant polysaccharides have been widely used in the medical field due to their special features and low toxicity. As an important drug delivery system, liposomes can not only encapsulate small-molecule compound but also big-molecule drug; therefore, they present great promise for the application of plant polysaccharides with unique physical and chemical properties and make remarkable successes. This paper summarized the current progress in plant polysaccharides liposomes, gave an overview on their experiment design method, preparation, and formulation, characterization and quality control, as well as in vivo and in vitro studies. Moreover, the potential application of plant polysaccharides liposomes was prospected as well.

  16. Internal radiotherapy and dosimetric study for {sup 111}In/{sup 177}Lu-pegylated liposomes conjugates in tumor-bearing mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang, H.-E. [Institute of Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Yu, H.-M. [Institute of Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Lu, Y.-C. [Institute of Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Heish, N.-N. [National Health Research Institute, Taipei, Taiwan (China); Tseng, Yun-Long [Taiwan Liposome Co. Ltd., Taipei, Taiwan (China); Huang, K.-L. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Chuang, K.-T. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Chen, Chin-Hsiung [Institute of Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Hwang, J.-J. [Institute of Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Lin, W.-J. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Wang, Shyh-Jen [Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Ting, G. [National Health Research Institute, Taipei, Taiwan (China); Whang-Peng, Jacqueline [National Health Research Institute, Taipei, Taiwan (China); Deng, W.-P. [Graduate Institute of Biomedical Materials, Taipei Medical University, Taipei, Taiwan (China)]. E-mail: wpdeng@tmu.edu.tw

    2006-12-20

    In vivo characterization and dosimetric analysis has been performed to evaluate the potential of pegylated liposomes as carriers of radionuclides in tumor internal radiotherapy. Methods: The DTPA/PEG-liposomes were synthesized with a medium size of 110 nm, conjugated with {sup 111}In/{sup 177}Lu-(oxine){sub 3} to afford {sup 111}In/{sup 177}Lu-liposome. The stability of {sup 111}In/{sup 177}Lu-liposome in serum was investigated. The biodistribution, scintigraphic imaging and pharmacokinetics of {sup 111}In/{sup 177}Lu-liposomes after intravenous(i.v.) injection into C-26 tumor-bearing BALB/cByJ mice were studied. Radiation dose was estimated by MIRD-III program. Results: The incorporation efficiency of {sup 111}In/{sup 177}Lu into liposomes was 95%. After incubation at 37 {sup o}C for 72 h in serum, more than 83% of radioactivity was still retained in the intact {sup 111}In/{sup 177}Lu-liposomes. The biodistribution of {sup 111}In-liposomes showed that the radioactivity in the blood decreased from 23.14{+-}8.16%ID/g at 1 h to 0.02{+-}0.00%ID/g at 72 h post-injection (p.i.), while reaching its maximum accumulation in tumors at 48 h p.i., with half-life in blood of 10.2 h. The results were supported by that of {sup 177}Lu-liposomes. Scintigraphic imaging with {sup 111}In-liposomes showed unambiguous tumor images at 48 h p.i. Dose estimation showed that the absorbed dose in tumor from {sup 177}Lu-liposomes was 5.74x10{sup -5} Gy/MBq. Conclusions: This study provides an in vivo characterization and dosimetric evaluation for the use of liposome systems as carriers in targeted radionuclide therapy. The results suggest that adequate tumor targeting as well as dose delivered to tumors could be achieved by the use of radionuclide targeted liposomes.

  17. Mitochondrial matrix delivery using MITO-Porter, a liposome-based carrier that specifies fusion with mitochondrial membranes

    International Nuclear Information System (INIS)

    Yasuzaki, Yukari; Yamada, Yuma; Harashima, Hideyoshi

    2010-01-01

    Mitochondria are the principal producers of energy in cells of higher organisms. It was recently reported that mutations and defects in mitochondrial DNA (mtDNA) are associated with various mitochondrial diseases including a variety of neurodegenerative and neuromuscular diseases. Therefore, an effective mitochondrial gene therapy and diagnosis would be expected to have great medical benefits. To achieve this, therapeutic agents need to be delivered into the innermost mitochondrial space (mitochondrial matrix), which contains the mtDNA pool. We previously reported on the development of MITO-Porter, a liposome-based carrier that introduces macromolecular cargos into mitochondria via membrane fusion. In this study, we provide a demonstration of mitochondrial matrix delivery and the visualization of mitochondrial genes (mtDNA) in living cells using the MITO-Porter. We first prepared MITO-Porter containing encapsulated propidium iodide (PI), a fluorescent dye used to stain nucleic acids to detect mtDNA. We then confirmed the emission of red-fluorescence from PI by conjugation with mtDNA, when the carriers were incubated in the presence of isolated rat liver mitochondria. Finally, intracellular observation by confocal laser scanning microscopy clearly verified that the MITO-Porter delivered PI to the mitochondrial matrix.

  18. Biophysical aspects of using liposomes as delivery vehicles.

    Science.gov (United States)

    Ulrich, Anne S

    2002-04-01

    Liposomes are used as biocompatible carriers of drugs, peptides, proteins, plasmic DNA, antisense oligonucleotides or ribozymes, for pharmaceutical, cosmetic, and biochemical purposes. The enormous versatility in particle size and in the physical parameters of the lipids affords an attractive potential for constructing tailor-made vehicles for a wide range of applications. Some of the recent literature will be reviewed here and presented from a biophysical point of view, thus providing a background for the more specialized articles in this special issue on liposome technology. Different properties (size, colloidal behavior, phase transitions, and polymorphism) of diverse lipid formulations (liposomes, lipoplexes, cubic phases, emulsions, and solid lipid nanoparticles) for distinct applications (parenteral, transdermal, pulmonary, and oral administration) will be rationalized in terms of common structural, thermodynamic and kinetic parameters of the lipids. This general biophysical basis helps to understand pharmaceutically relevant aspects such as liposome stability during storage and towards serum, the biodistribution and specific targeting of cargo, and how to trigger drug release and membrane fusion. Methods for the preparation and characterization of liposomal formulations in vitro will be outlined, too.

  19. Transcutaneous drug delivery by liposomes using fractional laser technology.

    Science.gov (United States)

    Fujimoto, Takahiro; Wang, Jian; Baba, Kazuki; Oki, Yuka; Hiruta, Yuki; Ito, Masayuki; Ito, Shinobu; Kanazawa, Hideko

    2017-07-01

    Transdermal delivery of hydrophilic peptides remains a challenge due to their poor cellular uptake and transdermal penetration. We hypothesize that combination of a CO 2 fractional laser to enhance percutaneous absorption and liposomes as transdermal carriers would improve skin penetration of hydrophilic drugs. NA. Liposomes were prepared using membrane fusion lipid dioleoylphosphatidylethanolamine, and used to deliver 5-carboxyfluorescein (CF) and fluorescein isothiocyanate-conjugated ovalbumin (OVA-FITC) as model hydrophilic peptide drugs. Liposome size was estimated by dynamic light scattering. Liposome uptake into murine macrophage cells and penetration or permeation into Yucatan micropig skin after irradiation by CO 2 fractional laser at varying energy levels (laser power and exposure duration) were investigated using Franz cell and fluorescence microscopy. Oxidative damage to the irradiated mouse skin was assessed by electron spin resonance. Size of CF and OVA-FITC encapsulated liposomes was 324 ± 75 nm. Cellular uptake of OVA-FITC delivered by liposomes was 10-fold higher (1,370 relative fluorescence units, RFU) than delivered in solution form (130 RFU). Fractional laser irradiation increased skin permeation rate of CF liposomes (0-10%) and OVA-FITC liposomes (4-40%) in a dose-dependent manner. Although peeling off the stratum corneum facilitated CF liposome penetration at low energy levels (2.69-3.29 J/cm 2 ; 10-20 W for 500 μs), drug permeation was similar (7-8%) in peeled or untreated skin at higher laser energy levels (6.06 J/cm 2 ; 20 W for 1,500 μs). FITC penetrated deeper in the skin after laser irradiation. However, OH, O2-, and VC reactive oxygen species were generated upon irradiation of the skin with a fractional CO 2 laser. Increasing laser power and irradiation, time increased liposome uptake by cells and penetration of peptide drugs across the skin in a dose-dependent manner. High-energy CO 2 fractional laser overcomes the

  20. Preparation of liposomes containing zedoary turmeric oil using freeze-drying of liposomes via TBA/water cosolvent systems and evaluation of the bioavailability of the oil.

    Science.gov (United States)

    Yang, Zhiwen; Yu, Songlin; Fu, Dahua

    2010-02-01

    The purpose of this study was to enhance the absorption of zedoary turmeric oil (ZTO) in vivo and develop new formulations of a water-insoluble oily drug. This study described a method for preparing ZTO liposomes, which involved freeze-drying (FD) of liposomes with TBA/water cosolvent systems. The TBA/water cosolvent systems were used to investigate a feasible method of liposomes manufacture; the two factors, sugar/lipid mass ratio and TBA content (concentration), of the preparation process were evaluated in this study. The results showed that the addition of TBA content could significantly enhance the sublimation of ice resulting in short FD cycles time, and reduce the entrapment efficiency of liposomes. In addition, the residual TBA solvents levels were determined to be less than 0.37% under all optimum formulations and processing conditions. Several physical properties of liposomes were examined by H-600 transmission electron microscope (TEM) and zetamaster analyser system. The results revealed that the liposomes were smooth and spherical with an average particle size of 457 +/- 7.8 nm and the zeta potential was more than 3.65 Mv. The bioavailability of the liposomes was evaluated in rabbits, compared with the conventional self-emulsifying formulation for oral administration. Compared with the conventional self-emulsifying formulation, the plasma concentration-time profiles with improved sustained-release characteristics were achieved after oral administration of the liposomes with a bioavailability of 257.7% (a good strategy for improving the bioavailability of an oily drug). In conclusion, the present experimental findings clearly demonstrated the usefulness of ZTO liposome vesicles in improving therapeutic efficacy by enhancing oral bioavailability. Our study offered an alternative method for designing sustained-release preparations of oily drugs.

  1. In Vitro and In Vivo Effective Gene Delivery with Novel Liposomal Bubbles

    Science.gov (United States)

    Nishiie, Norihito; Suzuki, Ryo; Oda, Yusuke; Hirata, Keiichi; Taira, Yuichiro; Utoguchi, Naoki; Negishi, Yoichi; Maruyama, Kazuo

    2010-03-01

    Microbubbles, which were ultrasound contrast agents, could improve the transfection efficiency by cavitation with ultrasound exposure. However, conventional microbubbles had some problems regarding size and targeting ability. To solve these problems, we paid attention to liposomes that had many advantages as drug, antigen and gene delivery carriers. Because they can easily be controlled their size and added a targeting function. And we succeeded to prepare novel liposomal bubbles (Bubble liposomes) entrapping perfluoropropane which was utilized for contrast enhancement in ultrasonography. In this study, we assessed the feasibility of Bubble liposomes as gene delivery tools utilized cavitation by ultrasound exposure. In vitro gene delivery, Bubble liposomes could deliver plasmid DNA to many cell types such as tumor cells, T cell line and endothelial cells without cytotoxicity. In vivo gene delivery, Bubble liposomes could effectively deliver plasmid DNA into mouse femoral artery. This method was more effectively than conventional lipofection. We conclude that Bubble liposomes are unique and efficient gene delivery tools in vitro and in vivo.

  2. Investigations of a new, highly negative liposome with improved biodistribution for imaging

    International Nuclear Information System (INIS)

    Hnatowich, D.J.; Clancy, B.

    1980-01-01

    An attractive feature of liposomes is the wide range of lipid composition that can lead to liposome formation, coupled with the observation that liposome biodistribution may be altered by varying lipid composition. For instance, adding charged lipids to neutral lecithin will alter the biodistribution of the resulting charged liposomes. We have prepared highly negative liposomes by replacing lecithin with negatively charged cardiolipin. The liposomes have been labeled in the lipid phase with Ga-67 and Tc-99m oxine and their properties evaluated. The expected high negative charge of the resulting liposomes was confirmed by an ion-exchange chromatographic technique. Using paper chromatography, the stability of the label was determined during incubation in saline and serum. Finally, biodistributions were determined at 2 h in mice, and the results compared with those for negative lecithin liposomes. Accumulated activities in liver and spleen were reduced by factors of five and 20, respectively, over lecithin liposomes. Since preferential accumulation of activity in these organs constitutes the biggest limitation to the use of lecithin liposomes, cardiolipin liposomes may prove to be more useful carriers of radioactivity in imaging applications. More importantly, however, these results illustrate the value of studying novel liposome types as potential radiopharmaceuticals

  3. Inhibitory effect of Lentinan entrapped in liposomes on hepatic metastasis in rats

    International Nuclear Information System (INIS)

    Yamashita, I.; Masuyama, K.; Yoshida, M.; Suzuki, Y.; Kasagi, T.; Tazawa, K.; Fujimaki, M.; Kawagoshi, T.; Maeda, M.; Honda, T.; Ochiai, H.

    1988-01-01

    Using the technique of Drug Delivery System, we experimentally attempted to examine whether the preventive i.v. administration of BRM entrapped in liposomes is useful or not for the cancer metastasis to the liver. As a BRM, we used Lentinan. The liposome used as a carrier in our study showed high stability both in vivo and in vitro with the mol ratio of phosphatidylcholine: cholesterol of 1. Also, high accumulation to reticuloendothelial system was evidenced. NK cell activity in the spleen and the liver on the day of the administration of AH60C hepatoma cells (2x10 6 cells) was higher by 1.3-2.3 times than those of the other groups. The survival ratio of tumor cells in the liver 8 h of tumor cells administration was significantly lower (P<0.01) than in the other groups. Rats with cancer metastasis to the liver on 30th day after the tumor cells administration were significantly decreased (P<0.01). These results suggested the usefulness of the i.v. administration of Lentinan entrapped in liposomes. (orig.)

  4. Potential of Cationic Liposomes as Adjuvants/Delivery Systems for Tuberculosis Subunit Vaccines.

    Science.gov (United States)

    Khademi, Farzad; Taheri, Ramezan Ali; Momtazi-Borojeni, Amir Abbas; Farnoosh, Gholamreza; Johnston, Thomas P; Sahebkar, Amirhossein

    2018-04-27

    The weakness of the BCG vaccine and its highly variable protective efficacy in controlling tuberculosis (TB) in different age groups as well as in different geographic areas has led to intense efforts towards the development and design of novel vaccines. Currently, there are several strategies to develop novel TB vaccines. Each strategy has its advantages and disadvantages. However, the most important of these strategies is the development of subunit vaccines. In recent years, the use of cationic liposome-based vaccines has been considered due to their capacity to elicit strong humoral and cellular immune responses against TB infections. In this review, we aim to evaluate the potential for cationic liposomes to be used as adjuvants/delivery systems for eliciting immune responses against TB subunit vaccines. The present review shows that cationic liposomes have extensive applications either as adjuvants or delivery systems, to promote immune responses against Mycobacterium tuberculosis (Mtb) subunit vaccines. To overcome several limitations of these particles, they were used in combination with other immunostimulatory factors such as TDB, MPL, TDM, and Poly I:C. Cationic liposomes can provide long-term storage of subunit TB vaccines at the injection site, confer strong electrostatic interactions with APCs, potentiate both humoral and cellular (CD4 and CD8) immune responses, and induce a strong memory response by the immune system. Therefore, cationic liposomes can increase the potential of different TB subunit vaccines by serving as adjuvants/delivery systems. These properties suggest the use of cationic liposomes to produce an efficient vaccine against TB infections.

  5. Oxygen Measurements in Liposome Encapsulated Hemoglobin

    Science.gov (United States)

    Phiri, Joshua Benjamin

    Liposome encapsulated hemoglobins (LEH's) are of current interest as blood substitutes. An analytical methodology for rapid non-invasive measurements of oxygen in artificial oxygen carriers is examined. High resolution optical absorption spectra are calculated by means of a one dimensional diffusion approximation. The encapsulated hemoglobin is prepared from fresh defibrinated bovine blood. Liposomes are prepared from hydrogenated soy phosphatidylcholine (HSPC), cholesterol and dicetylphosphate using a bath sonication method. An integrating sphere spectrophotometer is employed for diffuse optics measurements. Data is collected using an automated data acquisition system employing lock-in -amplifiers. The concentrations of hemoglobin derivatives are evaluated from the corresponding extinction coefficients using a numerical technique of singular value decomposition, and verification of the results is done using Monte Carlo simulations. In situ measurements are required for the determination of hemoglobin derivatives because most encapsulation methods invariably lead to the formation of methemoglobin, a nonfunctional form of hemoglobin. The methods employed in this work lead to high resolution absorption spectra of oxyhemoglobin and other derivatives in red blood cells and liposome encapsulated hemoglobin (LEH). The analysis using singular value decomposition method offers a quantitative means of calculating the fractions of oxyhemoglobin and other hemoglobin derivatives in LEH samples. The analytical methods developed in this work will become even more useful when production of LEH as a blood substitute is scaled up to large volumes.

  6. Lipophilic drug transfer between liposomal and biological membranes

    DEFF Research Database (Denmark)

    Fahr, Alfred; van Hoogevest, Peter; Kuntsche, Judith

    2006-01-01

    This review presents the current knowledge on the interaction of lipophilic, poorly water soluble drugs with liposomal and biological membranes. The center of attention will be on drugs having the potential to dissolve in a lipid membrane without perturbing them too much. The degree of interaction...... is described as solubility of a drug in phospholipid membranes and the kinetics of transfer of a lipophilic drug between membranes. Finally, the consequences of these two factors on the design of lipid-based carriers for oral, as well as parenteral use, for lipophilic drugs and lead selection of oral...... lipophilic drugs is described. Since liposomes serve as model-membranes for natural membranes, the assessment of lipid solubility and transfer kinetics of lipophilic drug using liposome formulations may additionally have predictive value for bioavailability and biodistribution and the pharmacokinetics...

  7. Micro- and Nano-Carrier Mediated Intra-Articular Drug Delivery Systems for the Treatment of Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Zhiyue Zhang

    2012-01-01

    Full Text Available The objective of this paper is to provide readers with current developments of intra-articular drug delivery systems. In recent years, although the search for a clinically successful ideal carrier is ongoing, sustained-release systems, such as polymeric micro- and nanoparticles, liposomes, and hydrogels, are being extensively studied for intra-articular drug delivery purposes. The advantages associated with long-acting preparations include a longer effect of the drug in the action site and a reduced risk of infection due to numerous injections consequently. This paper discusses the recent developments in the field of intra-articular sustained-release delivery systems for the treatment of osteoarthritis.

  8. Micro- and Nano-Carrier Mediated Intra-Articular Drug Delivery Systems for the Treatment of Osteoarthritis

    International Nuclear Information System (INIS)

    Zhang, Z.; Huang, G.

    2012-01-01

    The objective of this paper is to provide readers with current developments of intra-articular drug delivery systems. In recent years, although the search for a clinically successful ideal carrier is ongoing, sustained-release systems, such as polymeric micro- and nanoparticles, liposomes, and hydrogels, are being extensively studied for intra-articular drug delivery purposes. The advantages associated with long-acting preparations include a longer effect of the drug in the action site and a reduced risk of infection due to numerous injections consequently. This paper discusses the recent developments in the field of intra-articular sustained-release delivery systems for the treatment of osteoarthritis

  9. Drug targeting and the carriers. Application to chemoembolization and medical imaging

    International Nuclear Information System (INIS)

    Puisieux, F.; Benoit, J.P.; Roblot-Treupel, L.

    1987-01-01

    The last fifteen years have seen an increased interest in drug targeting which can be considered as a new way to control the body distribution of drugs when associated with an appropriate carrier. The systems currently studied possess different structures (macromolecular, vesicular and particular) and can be classified into carriers of first, second and third generation. After a brief review of the three types of carriers, this paper focuses on their respective interest in the different fields of radiology: carriers of first generation (microcapsules, microspheres) in chemoembolization, carriers of second generation (liposomes, nanocapsules, nanospheres) in conventional radiology, in computerized tomography, in scintigraphy, in RMN; carriers of third generation (monoclonal antibodies...) in immunoscintigraphy of tumors [fr

  10. Analysis of plasma protein adsorption onto DC-Chol-DOPE cationic liposomes by HPLC-CHIP coupled to a Q-TOF mass spectrometer

    KAUST Repository

    Capriotti, Anna Laura; Caracciolo, Giulio; Caruso, Giuseppe; Cavaliere, Chiara; Pozzi, Daniela; Samperi, Roberto; Laganà , Aldo

    2010-01-01

    Plasma protein adsorption is regarded as a key factor in the in vivo organ distribution of intravenously administered drug carriers, and strongly depends on vector surface characteristics. The present study aimed to characterize the "protein corona" absorbed onto DC-Chol-DOPE cationic liposomes. This system was chosen because it is one of the most efficient and widely used non-viral formulations in vitro and a potential candidate for in vivo transfection of genetic material. After incubation of human plasma with cationic liposomes, nanoparticle-protein complex was separated from plasma by centrifugation. An integrated approach based on protein separation by one-dimensional 12% polyacrylamide gel electrophoresis followed by the automated HPLC-Chip technology coupled to a high-resolution mass spectrometer was employed for protein corona characterization. Thirty gel lanes, approximately 2 mm, were cut, digested and analyzed by HPLC-MS/MS. Fifty-eight human plasma proteins adsorbed onto DC-Chol-DOPE cationic liposomes were identified. The knowledge of the interactions of proteins with liposomes can be exploited for future controlled design of colloidal drug carriers and possibly in the controlled creation of biocompatible surfaces of other devices that come into contact with proteins in body fluids. © 2010 Springer-Verlag.

  11. Analysis of plasma protein adsorption onto DC-Chol-DOPE cationic liposomes by HPLC-CHIP coupled to a Q-TOF mass spectrometer

    KAUST Repository

    Capriotti, Anna Laura

    2010-09-22

    Plasma protein adsorption is regarded as a key factor in the in vivo organ distribution of intravenously administered drug carriers, and strongly depends on vector surface characteristics. The present study aimed to characterize the "protein corona" absorbed onto DC-Chol-DOPE cationic liposomes. This system was chosen because it is one of the most efficient and widely used non-viral formulations in vitro and a potential candidate for in vivo transfection of genetic material. After incubation of human plasma with cationic liposomes, nanoparticle-protein complex was separated from plasma by centrifugation. An integrated approach based on protein separation by one-dimensional 12% polyacrylamide gel electrophoresis followed by the automated HPLC-Chip technology coupled to a high-resolution mass spectrometer was employed for protein corona characterization. Thirty gel lanes, approximately 2 mm, were cut, digested and analyzed by HPLC-MS/MS. Fifty-eight human plasma proteins adsorbed onto DC-Chol-DOPE cationic liposomes were identified. The knowledge of the interactions of proteins with liposomes can be exploited for future controlled design of colloidal drug carriers and possibly in the controlled creation of biocompatible surfaces of other devices that come into contact with proteins in body fluids. © 2010 Springer-Verlag.

  12. Fasudil and DETA NONOate, Loaded in a Peptide-Modified Liposomal Carrier, Slow PAH Progression upon Pulmonary Delivery.

    Science.gov (United States)

    Rashid, Jahidur; Nahar, Kamrun; Raut, Snehal; Keshavarz, Ali; Ahsan, Fakhrul

    2018-05-07

    We investigated the feasibility of a combination therapy comprising fasudil, a Rho-kinase inhibitor, and DETA NONOate (diethylenetriamine NONOate, DN), a long-acting nitric oxide donor, both loaded in liposomes modified with a homing peptide, CAR (CARSKNKDC), in the treatment of pulmonary arterial hypertension (PAH). We first prepared and characterized unmodified and CAR-modified liposomes of fasudil and DN. Using individual drugs alone or a mixture of fasudil and DN as controls, we studied the efficacy of the two liposomal preparations in reducing mean pulmonary arterial pressure (mPAP) in monocrotaline (MCT) and SUGEN-hypoxia-induced PAH rats. We also conducted morphometric studies (degree of muscularization, arterial medial wall thickness, and collagen deposition) after treating the PAH rats with test and control formulations. When the rats were treated acutely and chronically, the reduction in mPAP was more pronounced in the liposomal formulation-treated rats than in plain drug-treated rats. CAR-modified liposomes were more selective in reducing mPAP than unmodified liposomes of the drugs. Both drugs, formulated in CAR-modified liposomes, reduced the degree of muscularization, medial arterial wall thickness, and collagen deposition more than the combination of plain drugs did. As seen with the in vivo data, CAR-modified liposomes of fasudil or DN increased the levels of the vasodilatory signaling molecule, cGMP, in the smooth muscle cells of PAH-afflicted human pulmonary arteries. Overall, fasudil and DN, formulated in liposomes, could be used as a combination therapy for a better management of PAH.

  13. Development of a DNA-liposome complex for gene delivery applications

    Energy Technology Data Exchange (ETDEWEB)

    Rasoulianboroujeni, M. [Marquette University School of Dentistry, Milwaukee, WI 53233 (United States); Kupgan, G. [Department of Chemical Engineering, Oklahoma State University, 423 Engineering North, Stillwater, OK 74078 (United States); Moghadam, F. [School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ (United States); Tahriri, M. [Marquette University School of Dentistry, Milwaukee, WI 53233 (United States); Boughdachi, A. [Polymer Engineering Department, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Khoshkenar, P. [Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605 (United States); Ambrose, J.J. [Biomedical Engineering Department, Louisiana Tech University, Ruston, LA 71272 (United States); Kiaie, N. [Tissue Engineering Department, Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Vashaee, D. [Electrical and Computer Engineering Department, North Carolina State University, Raleigh, NC 27606 (United States); Ramsey, J.D. [Department of Chemical Engineering, Oklahoma State University, 423 Engineering North, Stillwater, OK 74078 (United States); Tayebi, L., E-mail: lobat.tayebi@marquette.edu [Marquette University School of Dentistry, Milwaukee, WI 53233 (United States)

    2017-06-01

    The association structures formed by cationic liposomes and DNA (Deoxyribonucleic acid)-liposome have been effectively utilized as gene carriers in transfection assays. In this research study, cationic liposomes were prepared using a modified lipid film hydration method consisting of a lyophilization step for gene delivery applications. The obtained results demonstrated that the mean particle size had no significant change while the polydispersity (PDI) increased after lyophilization. The mean particle size slightly reduced after lyophilization (520 ± 12 nm to 464 ± 25 nm) while the PDI increased after lyophilization (0.094 ± 0.017 to 0.220 ± 0.004). In addition. The mean particle size of vesicles increases when DNA is incorporated to the liposomes (673 ± 27 nm). According to the Scanning Electron Microscopy (SEM) and transmission electron microscopy (TEM) images, the spherical shape of liposomes confirmed their successful preservation and reconstitution from the powder. It was found that liposomal formulation has enhanced transfection considerably compared to the naked DNA as negative control. Finally, liposomal formulation in this research had a better function than Lipofectamine® 2000 as a commercialized product because the cellular activity (cellular protein) was higher in the prepared lipoplex than Lipofectamine® 2000. - Highlights: • Liposomal formulation in this research had a better function than Lipofectamine® 2000. • The average particle size had no significant change while the PDI increased after lyophilization. • LacZ expression of the developed cationic liposomes is approximately equal to the Lipofectamine® 2000.

  14. Integrated microfluidic devices for the synthesis of nanoscale liposomes and lipoplexes.

    Science.gov (United States)

    Balbino, Tiago A; Serafin, Juliana M; Radaic, Allan; de Jesus, Marcelo B; de la Torre, Lucimara G

    2017-04-01

    In this work, pDNA/cationic liposome (CL) lipoplexes for gene delivery were prepared in one-step using multiple hydrodynamic flow-focusing regions. The microfluidic platform was designed with two distinct regions for the synthesis of liposomes and the subsequent assembly with pDNA, forming lipoplexes. The obtained lipoplexes exhibited appropriate physicochemical characteristics for gene therapy applications under varying conditions of flow rate-ratio (FRR), total volumetric flow rate (Q T ) and pDNA content (molar charge ratio, R±). The CLs were able to condense and retain the pDNA in the vesicular structures with sizes ranging from 140nm to 250nm. In vitro transfection assays showed that the lipoplexes prepared in one step by the two-stage configuration achieved similar efficiencies as lipoplexes prepared by conventional bulk processes, in which each step comprises a series of manual operations. The integrated microfluidic platform generates lipoplexes with liposome formation combined in-line with lipoplex assembly, significantly reducing the number of steps usually required to form gene carrier systems. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Ultrasound Enhanced Matrix Metalloproteinase-9 Triggered Release of Contents from Echogenic Liposomes

    Science.gov (United States)

    Nahire, Rahul; Paul, Shirshendu; Scott, Michael D.; Singh, Raushan K.; Muhonen, Wallace W.; Shabb, John; Gange, Kara N.; Srivastava, D. K.; Sarkar, Kausik; Mallik, Sanku

    2012-01-01

    The extracellular enzyme matrix metalloproteinase-9 (MMP-9) is overexpressed in atherosclerotic plaques and in metastatic cancers. The enzyme is responsible for rupture of the plaques and for the invasion and metastasis of a large number of cancers. The ability of ultrasonic excitation to induce thermal and mechanical effects has been used to release drugs from different carriers. However, majority of these studies were performed with low frequency ultrasound (LFUS) at kHz frequencies. Clinical usage of LFUS excitations will be limited due to harmful biological effects. Herein, we report our results on the release of encapsulated contents from substrate lipopeptide incorporated echogenic liposomes triggered by recombinant human MMP-9. The contents release was further enhanced by the application of diagnostic frequency (3 MHz) ultrasound. The echogenic liposomes were successfully imaged employing a medical ultrasound transducer (4 – 15 MHz). The conditioned cell culture media from cancer cells (secreting MMP-9) released the encapsulated dye from the liposomes (30 – 50%) and this release is also increased (50 – 80%) by applying diagnostic frequency ultrasound (3 MHz) for 3 minutes. With further developments, these liposomes have the potential to serve as multimodal carriers for triggered release and simultaneous ultrasound imaging. PMID:22849291

  16. Gemcitabine treatment of rat soft tissue sarcoma with phosphatidyldiglycerol-based thermosensitive liposomes.

    Science.gov (United States)

    Limmer, Simone; Hahn, Jasmin; Schmidt, Rebecca; Wachholz, Kirsten; Zengerle, Anja; Lechner, Katharina; Eibl, Hansjörg; Issels, Rolf D; Hossann, Martin; Lindner, Lars H

    2014-09-01

    The pyrimidine analogue gemcitabine (dFdC) is frequently used in the treatment of patients with solid tumors. However, after i.v. application dFdC is rapidly inactivated by metabolization. Here, the potential of thermosensitive liposomes based on 1,2-dipalmitoyl-sn-glycero-3-phosphodiglycerol (DPPG2-TSL) were investigated as carrier and targeting system for delivery of dFdC in combination with local hyperthermia (HT). DPPG2-TSL were prepared by the lipid film hydration and extrusion method and characterized by dynamic light scattering, thin layer chromatography, phosphate assay and HPLC. In vivo experiments were performed in Brown Norway rats with a syngeneic soft tissue sarcoma. Local HT treatment was performed by light exposure. DPPG2-TSL were stable at 37°C in serum and showed a temperature dependent dFdC release >40°C. Plasma half-life of dFdC was strongly increased from 0.07 h (non-liposomal) to 0.53 h (liposomal, vesicle size 105 nm) or 2.59 h (liposomal, 129 nm). Therapy of BN175 tumors with dFdC encapsulated in DPPG2-TSL + HT showed significant improvement in tumor growth delay compared to non-liposomal dFdC without HT (p < 0.05), non-liposomal dFdC with HT (p < 0.01), and liposomal dFdC without HT (p < 0.05), respectively. Gemcitabine encapsulated in DPPG2-TSL in combination with local HT is a promising tool for the treatment of solid tumors. Therefore, these encouraging results ask for further investigation and evaluation.

  17. Drug-in-cyclodextrin-in-liposomes: A novel drug delivery system for flurbiprofen.

    Science.gov (United States)

    Zhang, Lina; Zhang, Qi; Wang, Xin; Zhang, Wenji; Lin, Congcong; Chen, Fen; Yang, Xinggang; Pan, Weisan

    2015-08-15

    A novel delivery system based on drug-cyclodextrin (CD) complexation and liposomes has been developed to improve therapeutic effect. Three different means, i.e., co-evaporation (COE), co-ground (GR) and co-lyophilization (COL) and three different CDs (β-CD, HP-β-CD and SBE-β-CD) were contrasted to investigate the characteristics of the end products. FP/FP-CD loaded liposomes were obtained by thin layer evaporation technique. Size, zeta potential and encapsulation efficiency were investigated by light scattering analysis and minicolumn centrifugation. Differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) showed the amorphous form of complexes and spherical morphology of FP-HP-β-CD COE loaded liposomes. The pH 7.4 phosphate buffer solution (PBS) was selected as the medium for the in vitro release. Wistar rats were put into use to study the pharmacokinetic behavior in vivo. FP-HP-β-CD COE loaded liposomes showed the better physicochemical characters that followed the average particle size, polydispersity index, zeta potential and mean encapsulation efficiency 158±10 nm, 0.19±0.1, -12.4±0.1 mW and 56.1±0.5%, separately. The relative bioavailability of FP-HP-β-CD COE loaded liposomes was 420%, 201% and 402% compared with FP solution, FP-HP-β-CD and FP-liposomes, respectively. In conclusion, the novel delivery system improved the relative bioavailability of FP significantly and provided a perspective way for delivery of insoluble drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Encapsulation of ropivacaine in a combined (donor-acceptor, ionic-gradient liposomal system promotes extended anesthesia time.

    Directory of Open Access Journals (Sweden)

    Camila Morais Gonçalves da Silva

    Full Text Available Ropivacaine is a local anesthetic with similar potency but lower systemic toxicity than bupivacaine, the most commonly used spinal anesthetic. The present study concerns the development of a combined drug delivery system for ropivacaine, comprised of two types of liposomes: donor multivesicular vesicles containing 250 mM (NH42SO4 plus the anesthetic, and acceptor large unilamellar vesicles with internal pH of 5.5. Both kinds of liposomes were composed of hydrogenated soy-phosphatidylcholine:cholesterol (2:1 mol% and were prepared at pH 7.4. Dynamic light scattering, transmission electron microscopy and electron paramagnetic resonance techniques were used to characterize the average particle size, polydispersity, zeta potential, morphology and fluidity of the liposomes. In vitro dialysis experiments showed that the combined liposomal system provided significantly longer (72 h release of ropivacaine, compared to conventional liposomes (~45 h, or plain ropivacaine (~4 h (p <0.05. The pre-formulations tested were significantly less toxic to 3T3 cells, with toxicity increasing in the order: combined system < ropivacaine in donor or acceptor liposomes < ropivacaine in conventional liposomes < plain ropivacaine. The combined formulation, containing 2% ropivacaine, increased the anesthesia duration up to 9 h after subcutaneous infiltration in mice. In conclusion, a promising drug delivery system for ropivacaine was described, which can be loaded with large amounts of the anesthetic (2%, with reduced in vitro cytotoxicity and extended anesthesia time.

  19. Evaluation of the avidin/biotin-liposome system injected in pleural space and peritoneum for drug delivery to mediastinal lymph nodes

    Science.gov (United States)

    Medina-Velazquez, Luis Alberto

    The avidin/biotin-liposome system is a new modality recently developed for targeting lymph nodes through the lymphatic system after local injection in a cavity as the route of delivery. In this dissertation we show that the avidin/biotin-liposome system has potential advantages over the injection of only liposomes for targeting lymph nodes. A goal of this dissertation was to evaluate the potential of pleural space as a route of transport for the targeting of mediastinal nodes. Another objective was to study the role of the injected dose of the avidin/biotin-liposome system for targeting mediastinal nodes. Dose, volume, site and sequence of injection of the agents were studied as factors that play an important role in the lymphatic targeting and in the organ distribution of liposomes after intracavitary injection of the avidin/biotin-liposome system. The hypothesis tested in this dissertation was that intracavitary injection of the avidin/biotin-liposome system in pleural space and/or peritoneum results in high levels of mediastinal node targeting with a significant reduction of unfavorable organ distribution when compared with the injection of only liposomes. The specific aims of this dissertation were: (1) to determine the pharmacokinetics, mediastinal node targeting, and biodistribution of avidin and biotin-liposomes injected individually in pleural and peritoneal space, (2) to determine the effect of injected dose and volume on the targeting of mediastinal nodes after intrapleural injection of the avidin/biotin-liposome system, and (3) to evaluate the dose effect of the avidin/biotin-liposome system on the targeting of mediastinal nodes and the lymphatics that drain the peritoneum and pleural space by injecting one agent in peritoneum and the corresponding agent in pleural space, and vice versa. To perform these studies, scintigraphic images were acquired with a gamma camera to non-invasively follow the pharmacokinetics and organ uptake of the avidin/biotin-liposome

  20. Immune mechanisms regulating pharmacokinetics and pharmacodynamics of PEGylated liposomal anticancer agents

    Science.gov (United States)

    Song, Gina

    Nanotechnology has made significant advances in drug delivery system for the treatment of cancer. Among various nanoparticle (NP) platforms, liposomes have been most widely used as a NP drug carrier for cancer therapy. High variation in pharmacokinetics (PK) and pharmacodynamics (PD) of liposome-based therapeutics has been reported. However, the interaction of liposome-based therapeutics with the immune system, specifically the mononuclear phagocyte system (MPS), and underlying molecular mechanisms for variable responses to liposomal drugs remain poorly understood. The objective of this dissertation was to elucidate immune mechanisms for the variable responses to PEGylated liposomal doxorubicin (PLD; DoxilRTM), a clinically relevant NP, in animal models and in patients. In vitro, in vivo and clinical systems were investigated to evaluate the effects of chemokines (CCL2 and CCL5), heterogeneity of the tumor microenvironment, and genetic variations on PK and PD of PLD. Results showed that there was a significantly positive linear relationship between PLD exposure (AUC) and total amount of CCL2 and CCL5, most prevalent chemokines in plasma, in patients with recurrent ovarian cancer. Consistent with these findings, preclinical studies using mice bearing SKOV3 orthotopic ovarian cancer xenografts demonstrated that PLD induced the production and secretion of chemokines into plasma. In addition, in vitro studies using human monocytic THP-1 cells demonstrated that PLD altered monocyte migration towards CCL2 and CCL5. The PK and efficacy studies of PLD in murine models of breast cancer showed that heterogeneous tumor microenvironment was associated with significantly different tumor delivery and efficacy of PLD, but not small molecule doxorubicin between two breast tumor models. A candidate genetic locus that was associated with clearance of PLD in 23 inbred mouse strains contains a gene that encodes for engulfment adapter PTB domain containing 1 (Gulp1). By using

  1. Determination of liposomal boron biodistribution in tumor bearing mice by using neutron capture autoradiography

    International Nuclear Information System (INIS)

    Yanagie, H.; Yasuhara, H.; Ogura, K.; Maruyama, K.; Matsumoto, T.; Skvarc, J.; Ilic, R.; Kuhne, G.; Eriguchi, M.; Kobayashi, H.

    2001-01-01

    It is necessary to accumulate the 10 B atoms selectively to the tumor cells for effective boron neutron capture therapy (BNCT). In order to achieve accurate measurements of 10 B concentrations in biological samples, we employ a technique of neutron capture autoradiography (NCAR) of the sliced whole body samples of tumor bearing mice using CR- 39 plastic track detectors. The CR-39 detectors attached with samples were exposed to thermal neutrons in the thermal column of the TRIGA II reactor at the Institute for Atomic Energy, Rikkyo University. We obtained NCAR images for mice injected intraveneously by 10 B-polyethylene-glycol (PEG) binding liposome or 10 B-bare liposome. The 10 B concentrations in the tumor tissue of mice were estimated by means of alpha and lithium track density measurements. In this study, we increased the accumulation of 10 B atoms in the tumor tissues by binding PEG chains to the surface of liposome, which increase the retension in the blood flow and escape the phagocytosis by reticulo-endotherial systems. Therefore, 10 B-PEG liposome is a candidate for an effective 10 B carrier in BNCT.(author)

  2. Gemcitabine-loaded liposomes: rationale, potentialities and future perspectives

    Directory of Open Access Journals (Sweden)

    Federico C

    2012-11-01

    Full Text Available Cinzia Federico, Valeria M Morittu, Domenico Britti, Elena Trapasso, Donato CoscoDepartment of Health Sciences, Building of BioSciences, University “Magna Græcia” of Catanzaro, Campus Universitario “S Venuta”, Germaneto, ItalyAbstract: This review describes the strategies used in recent years to improve the biopharmaceutical properties of gemcitabine, a nucleoside analog deoxycytidine antimetabolite characterized by activity against many kinds of tumors, by means of liposomal devices. The main limitation of using this active compound is the rapid inactivation of deoxycytidine deaminase following administration in vivo. Consequently, different strategies based on its encapsulation/complexation in innovative vesicular colloidal carriers have been investigated, with interesting results in terms of increased pharmacological activity, plasma half-life, and tumor localization, in addition to decreased side effects. This review focuses on the specific approaches used, based on the encapsulation of gemcitabine in liposomes, with particular attention to the results obtained during the last 5 years. These approaches represent a valid starting point in the attempt to obtain a novel, commercializable drug formulation as already achieved for liposomal doxorubicin (Doxil®, Caelyx®.Keywords: gemcitabine, liposomes, multidrug, poly(ethylene glycol, tumors

  3. Archaeosomes: an excellent carrier for drug and cell delivery.

    Science.gov (United States)

    Kaur, Gurmeet; Garg, Tarun; Rath, Goutam; Goyal, Amit K

    2016-09-01

    Archaeosomes as liposomes made with one or more ether lipids that are unique to the domain of Archaeobacteria, found in Archaea constitute a novel family of liposome. Achaean-type lipids consist of archaeol (diether) and/or caldarchaeol (tetraether) core structures. Archaeosomes can be produced using standard procedures (hydrated film submitted to sonication, extrusion and detergent dialysis) at any temperature in the physiological range or lower, therefore making it possible to encapsulate thermally stable compounds. Various physiological as well as environmental factors affect its stability. Archaeosomes are widely used as drug delivery systems for cancer vaccines, Chagas disease, proteins and peptides, gene delivery, antigen delivery and delivery of natural antioxidant compounds. In this review article, our major aim was to explore the applications of this new carrier system in pharmaceutical field.

  4. Recent Advances and Perspectives in Liposomes for Cutaneous Drug Delivery.

    Science.gov (United States)

    Carita, Amanda C; Eloy, Josimar O; Chorilli, Marlus; Lee, Robert J; Leonardi, Gislaine Ricci

    2018-02-13

    The cutaneous route is attractive for the delivery of drugs in the treatment of a wide variety of diseases. However the stratum corneum (SC) is an effective barrier that hampers skin penetration. Within this context, liposomes emerge as a potential carrier for improving topical delivery of therapeutic agents. In this review, we aimed to discuss key aspects for the topical delivery by drug-loaded liposomes. Phospholipid type and phase transition temperature have been shown to affect liposomal topical delivery. The effect of surface charge is subject to considerable variation depending on drug and composition. In addition, modified vesicles with the presence of components for permeation enhancement, such as surfactants and solvents, have been shown to have a considerable effect. These liposomes include: Transfersomes, Niosomes, Ethosomes, Transethosomes, Invasomes, coated liposomes, penetration enhancer containing vesicles (PEVs), fatty acids vesicles, Archaeosomes and Marinosomes. Furthermore, adding polymeric coating onto liposome surface could influence cutaneous delivery. Mechanisms of delivery include intact vesicular skin penetration, free drug diffusion, permeation enhancement, vesicle adsorption to and/or fusion with the SC, trans-appendageal penetration, among others. Finally, several skin conditions, including acne, melasma, skin aging, fungal infections and skin cancer, have benefited from liposomal topical delivery of drugs, with promising in vitro and in vivo results. However, despite the existence of some clinical trials, more studies are needed to be conducted in order to explore the potential of liposomes in the dermatological field. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Correlation between radioactivity and chemotherapeutics of the 111In-VNB-liposome in pharmacokinetics and biodistribution in rats

    Directory of Open Access Journals (Sweden)

    Tsai TH

    2012-02-01

    Full Text Available Wen-Chuan Lee1,*, Chih-Hsien Chang2,3,*, Chih-Min Huang1, Yu-Tse Wu1, Liang-Cheng Chen2, Chung-Li Ho2, Tsui-Jung Chang2, Te-Wei Lee2, Tung-Hu Tsai1,41Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, 2Division of Isotope Application, Institute of Nuclear Energy Research, Taoyuan, 3Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 4Department of Education and Research, Taipei City Hospital, Taipei, Taiwan*These authors contributed equally to this workBackground: The combination of a radioisotope with a chemotherapeutic agent in a liposomal carrier (ie, Indium-111-labeled polyethylene glycol pegylated liposomal vinorelbine, [111In-VNB-liposome] has been reported to show better therapeutic efficiency in tumor growth suppression. Nevertheless, the challenge remains as to whether this therapeutic effect is attributable to the combination of a radioisotope with chemotherapeutics. The goal of this study was to investigate the pharmacokinetics, biodistribution, and correlation of Indium-111 radioactivity and vinorelbine concentration in the 111In-VNB-liposome.Methods: The VNB-liposome and 111In-VNB-liposome were administered to rats. Blood, liver, and spleen tissue were collected to determine the distribution profile of the 111In-VNB-liposome. A liquid chromatography tandem mass spectrometry system and gamma counter were used to analyze the concentration of vinorelbine and radioactivity of Indium-111.Results: High uptake of the 111In-VNB-liposome in the liver and spleen demonstrated the properties of a nanosized drug delivery system. Linear regression showed a good correlation (r = 0.97 between Indium-111 radioactivity and vinorelbine concentration in the plasma of rats administered the 111In-VNB-liposome.Conclusion: A significant positive correlation between the pharmacokinetics and biodistribution of 111Indium radioactivity and vinorelbine in blood, spleen

  6. A liposomal steroid nano-drug for treating systemic lupus erythematosus.

    Science.gov (United States)

    Moallem, E; Koren, E; Ulmansky, R; Pizov, G; Barlev, M; Barenholz, Y; Naparstek, Y

    2016-10-01

    Glucocorticoids have been known for years to be the most effective therapy in systemic lupus erythematosus. Their use, however, is limited by the need for high doses due to their unfavorable pharmacokinetics and biodistribution. We have previously developed a novel liposome-based steroidal (methylprednisolone hemisuccinate (MPS)) nano-drug and demonstrated its specific accumulation in inflamed tissues, as well as its superior therapeutic efficacy over that of free glucocorticoids (non-liposomal) in the autoimmune diseases, including the adjuvant arthritis rat model and the experimental autoimmune encephalomyelitis mouse model. In the present work we have evaluated the therapeutic effect of the above liposome-based steroidal (MPS) nano-drug in the MRL-lpr/lpr murine model of SLE and compared it with similar doses of the free MPS. MRL-lpr/lpr mice were treated with daily injections of free MPS or weekly injections of 10% dextrose, empty nano-liposomes or the steroidal nano-drug and the course of their disease was followed up to the age of 24 weeks. Treatment with the steroidal nano-drug was found to be significantly superior to the free MPS in suppressing anti-dsDNA antibody levels, proliferation of lymphoid tissue and renal damage, and in prolonging survival of animals. This significant superiority of our liposome based steroidal nano-drug administered weekly compared with daily injections of free methylprednisolone hemisuccinate in suppressing murine lupus indicates this glucocorticoid nano-drug formulation may be a good candidate for the treatment of human SLE. © The Author(s) 2016.

  7. Carrier-Based Drug Delivery System for Treatment of Acne

    Science.gov (United States)

    Vyas, Amber; Kumar Sonker, Avinesh

    2014-01-01

    Approximately 95% of the population suffers at some point in their lifetime from acne vulgaris. Acne is a multifactorial disease of the pilosebaceous unit. This inflammatory skin disorder is most common in adolescents but also affects neonates, prepubescent children, and adults. Topical conventional systems are associated with various side effects. Novel drug delivery systems have been used to reduce the side effect of drugs commonly used in the topical treatment of acne. Topical treatment of acne with active pharmaceutical ingredients (API) makes direct contact with the target site before entering the systemic circulation which reduces the systemic side effect of the parenteral or oral administration of drug. The objective of the present review is to discuss the conventional delivery systems available for acne, their drawbacks, and limitations. The advantages, disadvantages, and outcome of using various carrier-based delivery systems like liposomes, niosomes, solid lipid nanoparticles, and so forth, are explained. This paper emphasizes approaches to overcome the drawbacks and limitations associated with the conventional system and the advances and application that are poised to further enhance the efficacy of topical acne formulations, offering the possibility of simplified dosing regimen that may improve treatment outcomes using novel delivery system. PMID:24688376

  8. S-thanatin functionalized liposome potentially targeting on Klebsiella pneumoniae and its application in sepsis mouse model

    Directory of Open Access Journals (Sweden)

    Xiaobo eFan

    2015-10-01

    Full Text Available S-thanatin (Ts was a short antimicrobial peptide with selective antibacterial activity. In this study, we aimed to design a drug carrier with specific bacterial targeting potential. The positively charged Ts was modified onto the liposome surface by linking Ts to the constituent lipids via a PEG linker. The benefits of this design were evaluated by preparing a series of liposomes and comparing their biological effects in vitro and in vivo. The particle size and Zeta potential of the constructed liposomes were measured with a Zetasizer Nano ZS system and a confocal laser scanning microscope (CLSM. The in vitro drug delivery potential was evaluated by measuring the cellular uptake of encapsulated levofloxacin using HPLC. Ts-linked liposome or its conjugates with quantum dots favored bacterial cells, and increased the bacterial uptake of levofloxacin. In antimicrobial assays, the Ts and levofloxacin combination showed a synergistic effect, and Ts-LPs-LEV exhibited excellent activity against the quality control stain Klebsiella pneumoniae ATCC 700603 and restored the susceptibility of multidrug-resistant K. pneumoniae clinical isolates to levofloxacin in vitro. Furthermore, Ts-LPs-LEV markedly reduced the lethality rate of the septic shock and resulted in rapid bacterial clearance in mouse models receiving clinical MDR isolates. These results suggest that the Ts-functionalized liposome may be a promising antibiotic delivery system for clinical infectious disorders caused by MDR bacteria, in particular the sepsis related diseases.

  9. EXPERIMENTAL LIPOSOMAL VIRAL VACCINE SAFETY

    Directory of Open Access Journals (Sweden)

    Romanova OA

    2016-12-01

    Full Text Available Introduction. With the transport links development there is rather important issue respiratory viral infections spread, especially influenza. The only method controlling influenza is vaccination. Search and development effective and safe vaccines is important. Material and methods. In base SO "Mechnikov Institute Microbiology and Immunology National Ukrainian Academy Medical Sciences" in the scientific theme "Developing new approaches to creating viral vaccines and study specific activity depending of type and degree component`s modification" was created several experimental influenza vaccine with subsequent component`s modification for selecting the most optimal pattern of safety and immunogenicity. In assessing the influenza vaccine safety is using a few criteria, including, reactivity, as measured by the frequency of local and systemic adverse (negative effects, which due to its introduction, and for lipid content drugs, ability to influence oxidation processes. At present study phase was determined: a systemic reaction and local reaction of delayed-type hypersensitivity (foot pad swelling assay;b lipids and proteins peroxidation processes after administration officinal and experimental vaccines (content protein’s carbonyl groups, lipid’s hydroperoxides, activity of glutathione-peroxidase.Study objects were trivalent seasonal influenza vaccine, "Vaxigrip" (Sanofi Pasteur, S.A., France, "Inflexal V" (Biotech Ltd. Berne, Switzerland and experimental vaccine samples. Highest immunogenicity vaccines had undergone improvements and modifications using adjuvant systems and acylation influenza proteins. Liposomes 2 – the experimental influenza vaccine with a liposome negative charge and antigenic composition like split vaccines "Vaksihryp". Liposomes 2.1 - the adjuvantexperimental influenza vaccine with modifications liposomal components (etoniy and chlorophyllipt molecules embedded in liposomal membrane. Liposomes 2.2 - the adjuvant

  10. Preparation and Characterization of Escherichia coli Liposomes as a New Drug Delivery System to Colon Cancer

    Directory of Open Access Journals (Sweden)

    Mohammad Kargar

    2016-06-01

    Full Text Available Introduction: Liposomes are spherical vesicles composed of concentric phospholipid bilayers that can entrap hydrophilic, hydrophobic drugs. Liposomes can be prepared from natural phospholipids, synthetic lipids or bacterial lipids. The aim of this study was to formulate liposome from bacterial lipids and evaluate physicochemical properties. Materials and methods: This study was performed experimentally on E.coli. The lipids were extracted from E.coli. using chloroform and methanol. Film method was used for preparing nano-systems and methylene blue was used as a drug model. Then their particle sizes were determined using particle sizer. The release methylene blue was carried out using dialysis membrane. Also, trailing them in cancer cells was evaluated by using carboxyfluorescein. Results: The average particle size of E.coli. liposomal was 338 nm. Encapsulation efficiency was 53.33 ± 2.88% and the value of release after 24 h was 97.54% ± 0.00. Liposomes could deliver the carboxyfluorescein to cancer cells. Discussion and conclusion: The results of this study demonstrated that bacterial liposome has probably a suitable nano-particle such as particle size and desirable loading and it is possible to use them as drug delivery system.

  11. Liposomes coated with thiolated chitosan enhance oral peptide delivery to rats☆

    Science.gov (United States)

    Gradauer, K.; Barthelmes, J.; Vonach, C.; Almer, G.; Mangge, H.; Teubl, B.; Roblegg, E.; Dünnhaupt, S.; Fröhlich, E.; Bernkop-Schnürch, A.; Prassl, R.

    2013-01-01

    The aim of the present study was the in vivo evaluation of thiomer-coated liposomes for an oral application of peptides. For this purpose, salmon calcitonin was chosen as a model drug and encapsulated within liposomes. Subsequently, the drug loaded liposomes were coated with either chitosan–thioglycolic acid (CS–TGA) or an S-protected version of the same polymer (CS–TGA–MNA), leading to an increase in the particle size of about 500 nm and an increase in the zeta potential from approximately − 40 mV to a maximum value of about + 44 mV, depending on the polymer. Coated liposomes were demonstrated to effectively penetrate the intestinal mucus layer where they came in close contact with the underlying epithelium. To investigate the permeation enhancing properties of the coated liposomes ex vivo, we monitored the transport of fluoresceinisothiocyanate-labeled salmon calcitonin (FITC-sCT) through rat small intestine. Liposomes coated with CS–TGA–MNA showed the highest effect, leading to a 3.8-fold increase in the uptake of FITC-sCT versus the buffer control. In vivo evaluation of the different formulations was carried out by the oral application of 40 μg of sCT per rat, either encapsulated within uncoated liposomes, CS–TGA-coated liposomes or CS–TGA–MNA-coated liposomes, or given as a solution serving as negative control. The blood calcium level was monitored over a time period of 24 h. The highest reduction in the blood calcium level, to a minimum of 65% of the initial value after 6 h, was achieved for CS–TGA–MNA-coated liposomes. Comparing the areas above curves (AAC) of the blood calcium levels, CS–TGA–MNA-coated liposomes led to an 8.2-fold increase compared to the free sCT solution if applied orally in the same concentration. According to these results, liposomes coated with S-protected thiomers have demonstrated to be highly valuable carriers for enhancing the oral bioavailability of salmon calcitonin. PMID:24140721

  12. Liposomes coated with thiolated chitosan enhance oral peptide delivery to rats.

    Science.gov (United States)

    Gradauer, K; Barthelmes, J; Vonach, C; Almer, G; Mangge, H; Teubl, B; Roblegg, E; Dünnhaupt, S; Fröhlich, E; Bernkop-Schnürch, A; Prassl, R

    2013-12-28

    The aim of the present study was the in vivo evaluation of thiomer-coated liposomes for an oral application of peptides. For this purpose, salmon calcitonin was chosen as a model drug and encapsulated within liposomes. Subsequently, the drug loaded liposomes were coated with either chitosan-thioglycolic acid (CS-TGA) or an S-protected version of the same polymer (CS-TGA-MNA), leading to an increase in the particle size of about 500 nm and an increase in the zeta potential from approximately -40 mV to a maximum value of about +44 mV, depending on the polymer. Coated liposomes were demonstrated to effectively penetrate the intestinal mucus layer where they came in close contact with the underlying epithelium. To investigate the permeation enhancing properties of the coated liposomes ex vivo, we monitored the transport of fluoresceinisothiocyanate-labeled salmon calcitonin (FITC-sCT) through rat small intestine. Liposomes coated with CS-TGA-MNA showed the highest effect, leading to a 3.8-fold increase in the uptake of FITC-sCT versus the buffer control. In vivo evaluation of the different formulations was carried out by the oral application of 40 μg of sCT per rat, either encapsulated within uncoated liposomes, CS-TGA-coated liposomes or CS-TGA-MNA-coated liposomes, or given as a solution serving as negative control. The blood calcium level was monitored over a time period of 24h. The highest reduction in the blood calcium level, to a minimum of 65% of the initial value after 6h, was achieved for CS-TGA-MNA-coated liposomes. Comparing the areas above curves (AAC) of the blood calcium levels, CS-TGA-MNA-coated liposomes led to an 8.2-fold increase compared to the free sCT solution if applied orally in the same concentration. According to these results, liposomes coated with S-protected thiomers have demonstrated to be highly valuable carriers for enhancing the oral bioavailability of salmon calcitonin. © 2013. Published by Elsevier B.V. All rights reserved.

  13. NIR responsive liposomal system for rapid release of drugs in cancer therapy

    Directory of Open Access Journals (Sweden)

    Chen MM

    2017-06-01

    Full Text Available Ming-Mao Chen,1 Yuan-Yuan Liu,1 Guang-Hao Su,2 Fei-Fei Song,1 Yan Liu,3 Qi-Qing Zhang1,4 1Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou, 2Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, 3State Key Lab of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 4Key Laboratory of Biomedical Material of Tianjin, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, People’s Republic of China Abstract: To design a rapid release liposomal system for cancer therapy, a NIR responsive bubble-generating thermosensitive liposome (BTSL system combined with photothermal agent (Cypate, doxorubicin (DOX, and NH4HCO3 was developed. Cypate/DOX-BTSL exhibited a good aqueous stability, photostability, and photothermal effect. In vitro release suggested that the amounts of DOX released from BTSL were obviously higher than that of (NH42SO4 liposomes at 42°C. After NIR irradiation, the hyperthermic temperature induced by Cypate led to the decomposition of NH4HCO3 and the generation of a large number of CO2 bubbles, triggering a rapid release of drugs. Confocal laser scanning microscope and acridine orange staining indicated that Cypate/DOX-BTSL upon irradiation could facilitate to disrupt the lysosomal membranes and realize endolysosomal escape into cytosol, improving the intracellular uptake of DOX clearly. MTT and trypan blue staining implied that the cell damage of Cypate/DOX-BTSL with NIR irradiation was more severe than that in the groups without irradiation. In vivo results indicated that Cypate/DOX-BTSL with irradiation could dramatically increase the accumulation of DOX in tumor, inhibit tumor growth, and reduce systemic side effects of DOX. These data demonstrated that Cypate/DOX-BTSL has the potential to be used as a NIR responsive liposomal system for a rapid

  14. Stimuli-Responsive Liposomes for Controlled Drug Delivery

    KAUST Repository

    Li, Wengang

    2014-09-01

    Liposomes are promising drug delivery vesicles due to their biodegradibility, large volume and biocompatibility towards both hydrophilic and hydrophobic drugs. They suffer, however, from poor stability which limits their use in controlled delivery applications. Herein, a novel method was devised for modification of liposomes with small molecules, polymers or nanoparticles to afford stimuli responsive systems that release on demand and stay relatively stable in the absence of the trigger.. This dissertation discusses thermosensitive, pH sensitive, light sensitive and magnetically triggered liposomes that have been prepared for controlled drug delivery application. RAFT polymerization was utilized for the preparation of thermosensitive liposomes (Cholesterol-PNIPAm) and acid-labile liposomes (DOPE-PAA). With low Mw Cholesterol-PNIPAm, the thermosensitive liposomes proved to be effective for controlled release and decreased the cytotoxicity of PNIPAm by eliciting the polymer doses. By crosslinking the DOPE-PAA on liposome surface with acid-labile diamine linkers, DOPE-PAA liposomes were verified to be sensitive at low pH. The effects of polymer structures (linear or hyperbranched) have also been studied for the stability and release properties of liposomes. Finally, a dual-responsive Au@SPIO embedded liposome hybrid (ALHs) was prepared with light-induced “on-and-off” function by photo-thermal process (visible light) and instant release properties triggered by alternating magnetic field, respectively. The ALH system would be further applied into the cellular imaging field as MRI contrast agent.

  15. Cardiovascular and behavioral effects produced by administration of liposome-entrapped GABA into the rat central nervous system.

    Science.gov (United States)

    Vaz, G C; Bahia, A P C O; de Figueiredo Müller-Ribeiro, F C; Xavier, C H; Patel, K P; Santos, R A S; Moreira, F A; Frézard, F; Fontes, M A P

    2015-01-29

    Liposomes are nanosystems that allow a sustained release of entrapped substances. Gamma-aminobutyric acid (GABA) is the most prevalent inhibitory neurotransmitter of the central nervous system (CNS). We developed a liposomal formulation of GABA for application in long-term CNS functional studies. Two days after liposome-entrapped GABA was injected intracerebroventricularly (ICV), Wistar rats were submitted to the following evaluations: (1) changes in mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) to ICV injection of bicuculline methiodide (BMI) in anesthetized rats; (2) changes in cardiovascular reactivity to air jet stress in conscious rats; and (3) anxiety-like behavior in conscious rats. GABA and saline-containing pegylated liposomes were prepared with a mean diameter of 200 nm. Rats with implanted cannulas targeted to lateral cerebral ventricle (n = 5-8/group) received either GABA solution (GS), empty liposomes (EL) or GABA-containing liposomes (GL). Following (48 h) central microinjection (2 μL, 0.09 M and 99 g/L) of liposomes, animals were submitted to the different protocols. Animals that received GL demonstrated attenuated response of RSNA to BMI microinjection (GS 48 ± 9, EL 43 ± 9, GL 11 ± 8%; P nervous system. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Dendritic cell targeted liposomes–protamine–DNA complexes mediated by synthetic mannosylated cholestrol as a potential carrier for DNA vaccine

    International Nuclear Information System (INIS)

    Li Pan; Chen Simu; Jiang Yuhong; Jiang Jiayu; Zhang Zhirong; Sun Xun

    2013-01-01

    To construct mannosylated liposomes/protamine/DNA (LPD) carriers for DNA vaccine targeting to dendritic cells (DCs), a mannosylated cholesterol derivative (Man-C6-Chol) was synthesized via simple ester linkage and amide bonds. Then, the Man-C6-Chol was applied to LPD formulation as a synthetic ligand. The physicochemical properties of mannosylated LPD (Man-LPD) were first evaluated, including the size and zeta potential, morphology and the ability to protect DNA against DNase I degradation. Man-LPD showed a small size with a stable viral-like structure. In comparison to non-mannose liposomes/LPD (Man-free liposomes/LPD), mannosylated liposomes/LPD (Man-liposomes/Man-LPD) exhibited higher efficiency in both intracellular uptake (2.3-fold) and transfection (4.5-fold) in vitro. Subsequent MTT assays indicated that the LPD carriers had low toxicity on the tested cells. Afterwards, the investigation into the maturation activation on primary bone marrow-derived DCs (BMDCs) showed that both Man-LPD and Man-free LPD induced remarkable up-regulation of CD80, CD86 and CD40 on BMDCs. Inspired by these studies, we can conclude that the synthetic mannosylated LPD targeting to DCs was a potential carrier for DNA vaccine. (paper)

  17. [Enhancing effect of Ulex europaeus agglutinin I modified liposomes on oral insulin absorption in mice].

    Science.gov (United States)

    Zhang, Na; Ping, Qi-neng; Xu, Wen-fang

    2004-12-01

    To investigate the enhancing effect on insulin absorption through GI. tract in mice by using the Ulex europaeus agglutinin I (UEA1) modified liposomes as the carrier. UEA1 modified phosphatidylethanolamine (PE) was prepared by conjugating method of 1-ethyl-3-(3'-dimethylaminopropyl) carbodiimide (EDC), then the modified compound (PE-UEA1) was incorporated into the conventional liposomes of insulin to obtain UEA1 modified liposomes. The agglutination test was performed to examine the UEA1 biological activities after synthesis and modification. When liposomes were applied to healthy mice or diabetic mice at insulin dose of 350 u x kg(-1) orally, the hypoglycemic effect was investigated according to the blood glucose level determination. The blood glucose levels of the healthy mice reduced by UEA1 modified liposomes were (84 +/- 15)% at 4 h, (78 +/- 11)% at 8 h and (90 +/- 12)% at 12 h after oral administration. The conventional liposomes and saline showed no effect. The blood glucose levels of the diabetic mice reduced by UEA1 modified liposomes were (73 +/- 7)% at 4 h, (74 +/- 9)% at 8 h, (86 +/- 9)% at 12 h after oral administration. The UEA1 modified liposomes promote the oral absorption of insulin due to the specific-site combination on M cell membrane.

  18. Development of paclitaxel-loaded liposomal systems with anti-her2 ...

    African Journals Online (AJOL)

    Methods: Seven different liposomal systems containing PTX, or MabHer2 or a combination of .... particle distribution via the polydispersity index ... at a constant voltage of 150 V for about 3h. ... using nano-drop spectrophotometer (BioSpec-.

  19. Liposomes containing cationic dimethyl dioctadecyl ammonium bromide: formulation, quality control, and lipofection efficiency.

    Science.gov (United States)

    Dass, Crispin R; Walker, Todd L; Burton, Mark A

    2002-01-01

    This article describes a novel, simple, and relatively inexpensive method to prepare cationic liposomes using an ethanol injection/pressure extrusion method. The study also demonstrated that binding erythrosine dye to cationic liposomes results in a shift of the absorption maximum of the dye from 528 nm to 549 nm at pH 4.25, allowing quantification and visualization of these vesicles. In addition, a relatively simple Ficoll-based gradient centrifugation method for separation of lipoplexes from unbound molecules is presented. Laboratory-formulated dimethyl dioctadecyl ammonium bromide (DDAB) containing liposomes were just as efficient in complexing nucleic acids as commercially available types, and binding increased as the positive to neutral lipid ratio was increased. Transfection efficiency of the DDAB-containing liposomes increased as the ratio of cationic to neutral lipid was increased from 1:1 to 4:1 with either PtdChol or DOPE as the neutral lipid. A concomitant increase in cytotoxicity of CSU-SA1 cancer cells was noted as the ratio of positive to neutral lipid of the liposomes was increased. Nevertheless, our present study showed that the 2:1 liposome is a good choice since it delivers functional plasmids at a comparable rate to commercial liposome formulations, has similar toxicities to the less harmful commercial liposomes, and is at least 1000-fold more economical to prepare inhouse, a major factor to be considered in preclinical and clinical studies with these carriers.

  20. Liposome as nanocarrier: Site targeted delivery in lung cancer

    Directory of Open Access Journals (Sweden)

    Najeeb Ullah

    2017-08-01

    Full Text Available Lung cancer is fatal and spreading rapidly worldwide. Different clinical strategies are applied to stop this cancer. As the lung is a delicate organ, special clinical applications must be used and nanodrugs delivery systems are the most important applications of all. This review discusses the lung problems such as lung cancer, lung inflammation and bronchi constrictions followed by repetitive intake of some drugs. The objective of this review is to study how nanodrug delivery systems were synthesized and used in lung disorder treatment especially in lung cancer. The authors studied some articles from 1989 to 2015. Liposome encapsulation was done in various ways for the delivery of different drugs such as metaproterenol into liposomes caused bronchodilation, immunoliposomes bearing antibodies for doxorubicin reduced 50% inhibitory effects, radioliposomes with high penetrating ability to peripheral airways, aerosol delivery systems with deep pulmonary deposition, polymeric drug delivery having potential to improve beneficial index of drug, solid lipid liposomes, liposomal gentamicin with altered different clinical susceptibilities of resistance, transferrin conjugated liposomes to deliver cytostatic drugs to site of lungs, anti-inflammatory drugs with mannosylated liposomes, liposomal suspensions with single stranded RNAs and peptide encapsulation of liposomes. This review indicates that many animals perished with intravenous administration of drugs but survived in liposomal targeting groups.

  1. Microbubbles coupled to methotrexate-loaded liposomes for ultrasound-mediated delivery of methotrexate across the blood–brain barrier

    Directory of Open Access Journals (Sweden)

    Wang X

    2014-10-01

    Full Text Available Xiang Wang,1 Ping Liu,1 Weixiao Yang,1 Lu Li,1 Peijing Li,2 Zheng Liu,1 Zhongxiong Zhuo,1 Yunhua Gao1 1Department of Ultrasound, Xinqiao Hospital of the Third Military Medical University, Chongqing, 2Department of Ultrasound, General Hospital of the Jinan Military Area, Jinan, People’s Republic of China Abstract: Methotrexate (MTX is the single most effective agent for the treatment of primary central nervous system lymphoma. Currently, the delivery of MTX to the brain is achieved by high systemic doses, which cause severe long-term neurotoxicity, or intrathecal administration, which is highly invasive and may lead to infections or hemorrhagic complications. Acoustically active microbubbles have been developed as drug carriers for the noninvasive and brain-targeted delivery of therapeutics. However, their application is limited by their low drug-loading capacity. To overcome this limitation, we prepared microbubbles coupled to MTX-loaded liposomes using ZHIFUXIAN, a novel type of microbubbles with a superior safety profile and long circulation time. MTX-liposome-coupled microbubbles had a high drug-loading capacity of 8.91%±0.86%, and their size (2.64±0.93 µm in diameter was suitable for intravenous injection. When used with ultrasound, they showed more potent in vitro cytotoxicity against Walker-256 cancer cells than MTX alone or MTX-loaded liposomes. When Sprague-Dawley rats were exposed to sonication, administration of these MTX-liposome-coupled microbubbles via the tail vein led to targeted disruption of the blood–brain barrier without noticeable tissue or capillary damage. High-performance liquid chromatography analysis of the brain MTX concentration showed that MTX delivery to the brain followed the order of MTX-liposome-coupled microbubbles + ultrasound (25.3±2.4 µg/g > unmodified ZHIFUXIAN + MTX + ultrasound (18.6±2.2 µg/g > MTX alone (6.97±0.75 µg/g > MTX-liposome-coupled microbubbles (2.92±0.39 µg/g. Therefore

  2. Protection of the organism with 2'-deoxycytidine hydrochloride encapsulated in liposomes, in the process of experimental radioprotective chemotherapy with cytosine arabinoside

    International Nuclear Information System (INIS)

    Bukhman, V.M.; Bekman, E.M.; Koval'skaya, N.I.

    1986-01-01

    The development of methods of selective protection of the organism from the toxic and immunodepressive effect of cytostatics is directed toward improvement of the results of the therapy of malignant neoplasms. In this work, the authors demonstrate the promise of the use of liposomes as a phagocytizable carrier for the protector substance, on the model of developing T-cell lymphoma EL4 of mice. The production of liposomes and 2'-Deoxycytidine hydrochloride encapsulated in liposomes is discussed

  3. Liposomal Tumor Targeting in Drug Delivery Utilizing MMP-2- and MMP-9-Binding Ligands

    Directory of Open Access Journals (Sweden)

    Oula Penate Medina

    2011-01-01

    Full Text Available Nanotechnology offers an alternative to conventional treatment options by enabling different drug delivery and controlled-release delivery strategies. Liposomes being especially biodegradable and in most cases essentially nontoxic offer a versatile platform for several different delivery approaches that can potentially enhance the delivery and targeting of therapies to tumors. Liposomes penetrate tumors spontaneously as a result of fenestrated blood vessels within tumors, leading to known enhanced permeability and subsequent drug retention effects. In addition, liposomes can be used to carry radioactive moieties, such as radiotracers, which can be bound at multiple locations within liposomes, making them attractive carriers for molecular imaging applications. Phage display is a technique that can deliver various high-affinity and selectivity peptides to different targets. In this study, gelatinase-binding peptides, found by phage display, were attached to liposomes by covalent peptide-PEG-PE anchor creating a targeted drug delivery vehicle. Gelatinases as extracellular targets for tumor targeting offer a viable alternative for tumor targeting. Our findings show that targeted drug delivery is more efficient than non-targeted drug delivery.

  4. Phospholipid liposomes functionalized by protein

    Science.gov (United States)

    Glukhova, O. E.; Savostyanov, G. V.; Grishina, O. A.

    2015-03-01

    Finding new ways to deliver neurotrophic drugs to the brain in newborns is one of the contemporary problems of medicine and pharmaceutical industry. Modern researches in this field indicate the promising prospects of supramolecular transport systems for targeted drug delivery to the brain which can overcome the blood-brain barrier (BBB). Thus, the solution of this problem is actual not only for medicine, but also for society as a whole because it determines the health of future generations. Phospholipid liposomes due to combination of lipo- and hydrophilic properties are considered as the main future objects in medicine for drug delivery through the BBB as well as increasing their bioavailability and toxicity. Liposomes functionalized by various proteins were used as transport systems for ease of liposomes use. Designing of modification oligosaccharide of liposomes surface is promising in the last decade because it enables the delivery of liposomes to specific receptor of human cells by selecting ligand and it is widely used in pharmacology for the treatment of several diseases. The purpose of this work is creation of a coarse-grained model of bilayer of phospholipid liposomes, functionalized by specific to the structural elements of the BBB proteins, as well as prediction of the most favorable orientation and position of the molecules in the generated complex by methods of molecular docking for the formation of the structure. Investigation of activity of the ligand molecule to protein receptor of human cells by the methods of molecular dynamics was carried out.

  5. Structure relationship of cationic lipids on gene transfection mediated by cationic liposomes.

    Science.gov (United States)

    Paecharoenchai, Orapan; Niyomtham, Nattisa; Apirakaramwong, Auayporn; Ngawhirunpat, Tanasait; Rojanarata, Theerasak; Yingyongnarongkul, Boon-ek; Opanasopit, Praneet

    2012-12-01

    The aim of this study was to investigate the transfection efficiency of cationic liposomes formulated with phosphatidylcholine (PC) and novel synthesized diethanolamine-based cationic lipids at a molar ratio of 5:1 in comparison with Lipofectamine™ 2000. Factors affecting transfection efficiency and cell viability, including the chemical structure of the cationic lipids, such as different amine head group (diamine and polyamine; and non-spermine and spermine) and acyl chain lengths (C14, C16, and C18) and the weight ratio of liposomes to DNA were evaluated on a human cervical carcinoma cell line (HeLa cells) using the pDNA encoding green fluorescent protein (pEGFP-C2). Characterizations of these lipoplexes in terms of size and charge measurement and agarose gel electrophoresis were performed. The results from this study revealed that almost no transfection was observed in the liposome formulations composed of cationic lipids with a non-spermine head group. In addition, the transfection efficiency of these cationic liposomes was in the following order: spermine-C14 > spermine-C16 > spermine-C18. The highest transfection efficiency was observed in the formulation of spermine-C14 liposomes at a weight ratio of 25; furthermore, this formulation was safe for use in vitro. In conclusion, cationic liposomes containing spermine head groups demonstrated promising potential as gene carriers.

  6. Liposomal curcumin and its application in cancer.

    Science.gov (United States)

    Feng, Ting; Wei, Yumeng; Lee, Robert J; Zhao, Ling

    2017-01-01

    Curcumin (CUR) is a yellow polyphenolic compound derived from the plant turmeric. It is widely used to treat many types of diseases, including cancers such as those of lung, cervices, prostate, breast, bone and liver. However, its effectiveness has been limited due to poor aqueous solubility, low bioavailability and rapid metabolism and systemic elimination. To solve these problems, researchers have tried to explore novel drug delivery systems such as liposomes, solid dispersion, microemulsion, micelles, nanogels and dendrimers. Among these, liposomes have been the most extensively studied. Liposomal CUR formulation has greater growth inhibitory and pro-apoptotic effects on cancer cells. This review mainly focuses on the preparation of liposomes containing CUR and its use in cancer therapy.

  7. Octanol-assisted liposome assembly on chip

    Science.gov (United States)

    Deshpande, Siddharth; Caspi, Yaron; Meijering, Anna E. C.; Dekker, Cees

    2016-01-01

    Liposomes are versatile supramolecular assemblies widely used in basic and applied sciences. Here we present a novel microfluidics-based method, octanol-assisted liposome assembly (OLA), to form monodisperse, cell-sized (5-20 μm), unilamellar liposomes with excellent encapsulation efficiency. Akin to bubble blowing, an inner aqueous phase and a surrounding lipid-carrying 1-octanol phase is pinched off by outer fluid streams. Such hydrodynamic flow focusing results in double-emulsion droplets that spontaneously develop a side-connected 1-octanol pocket. Owing to interfacial energy minimization, the pocket splits off to yield fully assembled solvent-free liposomes within minutes. This solves the long-standing fundamental problem of prolonged presence of residual oil in the liposome bilayer. We demonstrate the unilamellarity of liposomes with functional α-haemolysin protein pores in the membrane and validate the biocompatibility by inner leaflet localization of bacterial divisome proteins (FtsZ and ZipA). OLA offers a versatile platform for future analytical tools, delivery systems, nanoreactors and synthetic cells.

  8. Clove essential oil-in-cyclodextrin-in-liposomes in the aqueous and lyophilized states: From laboratory to large scale using a membrane contactor.

    Science.gov (United States)

    Sebaaly, Carine; Charcosset, Catherine; Stainmesse, Serge; Fessi, Hatem; Greige-Gerges, Hélène

    2016-03-15

    This work is dedicated to prepare liposomal dry powder formulations of inclusion complexes of clove essential oil (CEO) and its main component eugenol (Eug). Ethanol injection method and membrane contactor were applied to prepare liposomes at laboratory and large scale, respectively. Various liposomal formulations were tested: (1) free hydroxypropyl-β-cyclodextrin loaded liposomes; (2) drug in hydroxypropyl-β-cyclodextrin in liposomes (DCL); (3) DCL2 obtained by double loading technique, where the drug is added in the organic phase and the inclusion complex in the aqueous phase. Liposomes were characterized for their particle size, polydispersity index, Zeta potential, morphology, encapsulation efficiency of CEO components and Eug loading rate. Reproducible results were obtained with both injection devices. Compared to Eug-loaded liposomes, DCL and DCL2 improved the loading rate of Eug and possessed smaller vesicles size. The DPPH(•) scavenging activity of Eug and CEO was maintained upon incorporation of Eug and CEO into DCL and DCL2. Contrary to DCL2, DCL formulations were stable after 1 month of storage at 4°C and upon reconstitution of the dried lyophilized cakes. Hence, DCL in aqueous and lyophilized forms, are considered as a promising carrier system to preserve volatile and hydrophobic drugs enlarging their application in cosmetic, pharmaceutical and food industries. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Liposomal Formulations in Clinical Use: An Updated Review

    Directory of Open Access Journals (Sweden)

    Upendra Bulbake

    2017-03-01

    Full Text Available Liposomes are the first nano drug delivery systems that have been successfully translated into real-time clinical applications. These closed bilayer phospholipid vesicles have witnessed many technical advances in recent years since their first development in 1965. Delivery of therapeutics by liposomes alters their biodistribution profile, which further enhances the therapeutic index of various drugs. Extensive research is being carried out using these nano drug delivery systems in diverse areas including the delivery of anti-cancer, anti-fungal, anti-inflammatory drugs and therapeutic genes. The significant contribution of liposomes as drug delivery systems in the healthcare sector is known by many clinical products, e.g., Doxil®, Ambisome®, DepoDur™, etc. This review provides a detailed update on liposomal technologies e.g., DepoFoam™ Technology, Stealth technology, etc., the formulation aspects of clinically used products and ongoing clinical trials on liposomes.

  10. Mucus interactions with liposomes encapsulating bioactives: Interfacial tensiometry and cellular uptake on Caco-2 and cocultures of Caco-2/HT29-MTX.

    Science.gov (United States)

    Li, Yang; Arranz, Elena; Guri, Anilda; Corredig, Milena

    2017-02-01

    Structuring of delivery matrices in foods aquires careful designing for optimal delivery and subsiquent absorption of the beneficial compounds in the gut. There has been quite improvement in mimicking digestion and absorption in vitro but as of yet little is understood on mucus interference in nutrient absorption Therefore in this study interactions of human intestinal mucus with milk and soy phospholipids liposomes carring hydrophilic (epigallocatechin-3-gallate) or hydrophobic (β-carotene) bioactive molecules were investigated. Liposomes of about 100nm were obtained using microfluidization and their behaviour with the human intestinal mucus were evaluated using drop shape tensiometry. The chemistry of the liposomes (milk or soy) and the encapsulated bioactive structure can affect the viscoelastic behaviour of the complex itself. Empty or loaded liposomes were differently interacting with the mucus at the interface. Mucus-liposomes interactions were also studied using cell cultures, Caco-2 (without mucus) and cocultures Caco-2/HT29-MTX (mucus producing). The interaction of mucus layer with liposomes was at some extent aligned with rheological studies. This work demonstrated that delivery systems may interact with the mucosal surface of intestinal cells, and in vitro approaches allow for screening of such interactions. These highlights could help us in carefully designing the delivery systems and moreover choosing the right carrier and/or bioactive that does not jeopardize the optimal delivery of the bioactive structure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Phytosome and Liposome: The Beneficial Encapsulation Systems in Drug Delivery and Food Application

    Directory of Open Access Journals (Sweden)

    Nayyer Karimi

    2015-06-01

    Full Text Available Due to poor solubility in lipids, many of bioactive components (Nutraceutical materials show less bioactivity than optimal state in water solution. Phytosomes improve absorption and bioavailability of biomaterials. Liposomes, spherical shaped nanocarriers, were discovered in the 1960s by bangham. Due to their composition, variability and structural properties, liposomes and phytosomes are extremely versatile, leading to a large number of applications including pharmaceutical, cosmetics and food industrial fields. They are advanced forms of herbal formulations containing the bioactive phytoconstituents of herb extracts such as flavonoids, glycosides and terpenoids, which have good ability to transit from a hydrophilic environment into the lipid friendly environment of the outer cell membrane. They have better bioavailability and actions than the conventional herbal extracts containing dosage. Phytosome technology has increasing effect on the bioavailability of herbal extracts including ginkgo biloba, grape seed, green tea, milk thistle, ginseng, etc., and can be developed for various therapeutic uses or dietary supplements. Liposomes are composed of bilayer membranes, which are made of lipid molecules. They form when phospholipids are dispersed in aqueous media and exposed to high shear rates by using micro-fluidization or colloid mill. The mechanism for formation of liposomes is mainly the hydrophilic–hydrophobic interactions between phospholipids and water molecules. Here, we attempt to review the features of phytosomes and liposomes as well as their preparation methods and capacity in food and drug applications. Generally, it is believed that phytosomes and liposomes are suitable delivery systems for nutraceuticals, and can be widely used in food industry.

  12. Advances and Challenges of Liposome Assisted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Lisa eSercombe

    2015-12-01

    Full Text Available The application of liposomes to assist drug delivery has already had a major impact on many biomedical areas. They have been shown to be beneficial for stabilizing therapeutic compounds, overcoming obstacles to cellular and tissue uptake, and improving biodistribution of compounds to target sites in vivo. This enables effective delivery of encapsulated compounds to target sites while minimizing systemic toxicity. Liposomes present as an attractive delivery system due to their flexible physicochemical and biophysical properties, which allow easy manipulation to address different delivery considerations. Despite considerable research in the last 50 years and the plethora of positive results in preclinical studies, the clinical translation of liposome assisted drug delivery platforms has progressed incrementally. In this review, we will discuss the advances in liposome assisted drug delivery, biological challenges that still remain, and current clinical and experimental use of liposomes for biomedical applications. The translational obstacles of liposomal technology will also be presented.

  13. Liposomal membrane disruption by means of miniaturized dielectric-barrier discharge in air: liposome characterization

    Science.gov (United States)

    Svarnas, P.; Asimakoulas, L.; Katsafadou, M.; Pachis, K.; Kostazos, N.; Antimisiaris, S. G.

    2017-08-01

    The increasing interest of the plasma community in the application of atmospheric-pressure cold plasmas to bio-specimen treatment has led to the creation of the emerging field of plasma biomedicine. Accordingly, plasma setups based on dielectric-barrier discharges have already been widely tested for the inactivation of various cells. Most of these systems refer to the plasma jet concept where noble gases penetrate atmospheric air and are subjected to the influence of high electric fields, thus forming guided streamers. Following the original works of our group where liposomal membranes were proposed as models for studying the interaction between plasma jets and cells, we present herein a study on liposomal membrane disruption by means of miniaturized dielectric-barrier discharge running in atmospheric air. Liposomal membranes of various lipid compositions, lamellarities, and sizes are treated at different times. It is shown that the dielectric-barrier discharge of low mean power leads to efficient liposomal membrane disruption. The latter is achieved in a controllable manner and depends on liposome properties. Additionally, it is clearly demonstrated that liposomal membrane disruption takes place even after plasma extinction, i.e. during post-treatment, resembling thus an ‘apoptosis’ effect, which is well known today mainly for cell membranes. Thus, the adoption of the present concept would be beneficial for tailoring studies on plasma-treated cell-mimics. Finally, the liposome treatment is discussed with respect to possible physicochemical mechanisms and potential discharge modification due to the various compositions of the liquid electrode.

  14. Enzymatic degradation of polymer covered SOPC-liposomes in relation to drug delivery

    DEFF Research Database (Denmark)

    Davidsen, Jesper; Vermehren, C.; Frøkjær, S.

    2001-01-01

    Polyethylenoxide (PEG) covered liposomes are used as lipid-based drug-delivery systems. In comparison to conventional liposomes the polymer-covered liposomes display a long circulation half-life in the blood stream. We investigate the influence of polyethyleneoxide-distearoylphosphatidylethanolam......Polyethylenoxide (PEG) covered liposomes are used as lipid-based drug-delivery systems. In comparison to conventional liposomes the polymer-covered liposomes display a long circulation half-life in the blood stream. We investigate the influence of polyethyleneoxide...

  15. Comparison of the adverse event profiles of conventional and liposomal formulations of doxorubicin using the FDA adverse event reporting system.

    Science.gov (United States)

    Fukuda, Akiho; Tahara, Kohei; Hane, Yuuki; Matsui, Toshinobu; Sasaoka, Sayaka; Hatahira, Haruna; Motooka, Yumi; Hasegawa, Shiori; Naganuma, Misa; Abe, Junko; Nakao, Satoshi; Takeuchi, Hirofumi; Nakamura, Mitsuhiro

    2017-01-01

    Doxorubicin (DOX) is an anthracycline widely used for the treatment of solid and hematological tumors. The aim of this study was to assess the adverse event profiles of conventional DOX and liposomal DOX. This is the first study to evaluate the effect of a liposomal formulation of DOX using spontaneous reporting system (SRS) databases. The SRS used was the US Food and Drug Administration Adverse Event Reporting System (FAERS). This study relied on definitions of preferred terms provided by the Medical Dictionary for Regulatory Activities (MedDRA) and the standardized MedDRA Queries (SMQ) database. We also calculated the reporting odds ratios (RORs) of suspected drugs (conventional DOX; PEGylated-liposome DOX; non-PEGylated-liposome DOX). The FAERS database contained 7,561,254 reports from January 2004 to December 2015. The number of reported AE cases for conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX was 5039, 3780, and 349, respectively. Conventional DOX and liposomal DOX have potential risks of causing myelosuppression, cardiotoxicity, alopecia, nausea, and vomiting, among other effects. The RORs (95% CI) from SMQ for haematopoietic leucopenia associated with conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX were 12.75 (11.89-13.68), 6.43 (5.81-7.13), and 14.73 (11.42-18.99), respectively. Liposomal DOX formulations were associated with lower RORs with regard to myelosuppression, cardiotoxicity, and alopecia than the conventional DOX was. The RORs (95% CI) for palmar-plantar erythrodysesthesia (PPE) associated with conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX were 6.56 (4.74-9.07), 64.77 (56.84-73.80), and 28.76 (15.77-52.45), respectively. This study is the first to evaluate the relationship between DOX liposomal formulations and their adverse event profiles. The results indicate that careful observation for PPE is recommended with the use of liposomal DOX, especially PEGylated-liposome

  16. Comparison of the adverse event profiles of conventional and liposomal formulations of doxorubicin using the FDA adverse event reporting system.

    Directory of Open Access Journals (Sweden)

    Akiho Fukuda

    Full Text Available Doxorubicin (DOX is an anthracycline widely used for the treatment of solid and hematological tumors. The aim of this study was to assess the adverse event profiles of conventional DOX and liposomal DOX. This is the first study to evaluate the effect of a liposomal formulation of DOX using spontaneous reporting system (SRS databases. The SRS used was the US Food and Drug Administration Adverse Event Reporting System (FAERS. This study relied on definitions of preferred terms provided by the Medical Dictionary for Regulatory Activities (MedDRA and the standardized MedDRA Queries (SMQ database. We also calculated the reporting odds ratios (RORs of suspected drugs (conventional DOX; PEGylated-liposome DOX; non-PEGylated-liposome DOX. The FAERS database contained 7,561,254 reports from January 2004 to December 2015. The number of reported AE cases for conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX was 5039, 3780, and 349, respectively. Conventional DOX and liposomal DOX have potential risks of causing myelosuppression, cardiotoxicity, alopecia, nausea, and vomiting, among other effects. The RORs (95% CI from SMQ for haematopoietic leucopenia associated with conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX were 12.75 (11.89-13.68, 6.43 (5.81-7.13, and 14.73 (11.42-18.99, respectively. Liposomal DOX formulations were associated with lower RORs with regard to myelosuppression, cardiotoxicity, and alopecia than the conventional DOX was. The RORs (95% CI for palmar-plantar erythrodysesthesia (PPE associated with conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX were 6.56 (4.74-9.07, 64.77 (56.84-73.80, and 28.76 (15.77-52.45, respectively. This study is the first to evaluate the relationship between DOX liposomal formulations and their adverse event profiles. The results indicate that careful observation for PPE is recommended with the use of liposomal DOX, especially PEGylated-liposome

  17. Long-circulating liposomes radiolabeled with [18F]fluorodipalmitin ([18F]FDP)

    International Nuclear Information System (INIS)

    Marik, Jan; Tartis, Michaelann S.; Zhang, Hua; Fung, Jennifer Y.; Kheirolomoom, Azadeh; Sutcliffe, Julie L.; Ferrara, Katherine W.

    2007-01-01

    Synthesis of a radiolabeled diglyceride, 3-[ 18 F]fluoro-1,2-dipalmitoylglycerol [[ 18 F]fluorodipalmitin ([ 18 F]FDP)], and its potential as a reagent for radiolabeling long-circulating liposomes were investigated. The incorporation of 18 F into the lipid molecule was accomplished by nucleophilic substitution of the p-toluenesulfonyl moiety with a decay-corrected yield of 43±10% (n=12). Radiolabeled, long-circulating polyethylene-glycol-coated liposomes were prepared using a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethyleneglycol)-2000] ammonium salt (61:30:9) and [ 18 F]FDP with a decay-corrected yield of 70±8% (n=4). PET imaging and biodistribution studies were performed with free [ 18 F]FDP and liposome-incorporated [ 18 F]FDP. Freely injected [ 18 F]FDP had the highest uptake in the liver, spleen and lungs. Liposomal [ 18 F]FDP remained in blood circulation at near-constant levels for at least 90 min, with a peak concentration near 2.5%ID/cc. Since [ 18 F]FDP was incorporated into the phospholipid bilayer, it could potentially be used for radiolabeling a variety of lipid-based drug carriers

  18. Liposomal bupivacaine: a review of a new bupivacaine formulation

    Directory of Open Access Journals (Sweden)

    Chahar P

    2012-08-01

    Full Text Available Praveen Chahar, Kenneth C Cummings IIIAnesthesiology Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USAAbstract: Many attempts have been made to increase the duration of local anesthetic action. One avenue of investigation has focused on encapsulating local anesthetics within carrier molecules to increase their residence time at the site of action. This article aims to review the literature surrounding the recently approved formulation of bupivacaine, which consists of bupivacaine loaded in multivesicular liposomes. This preparation increases the duration of local anesthetic action by slow release from the liposome and delays the peak plasma concentration when compared to plain bupivacaine administration. Liposomal bupivacaine has been approved by the US Food and Drug Administration for local infiltration for pain relief after bunionectomy and hemorrhoidectomy. Studies have shown it to be an effective tool for postoperative pain relief with opioid sparing effects and it has also been found to have an acceptable adverse effect profile. Its kinetics are favorable even in patients with moderate hepatic impairment, and it has been found not to delay wound healing after orthopedic surgery. More studies are needed to establish its safety and efficacy for use via intrathecal, epidural, or perineural routes. In conclusion, liposomal bupivacaine is effective for treating postoperative pain when used via local infiltration when compared to placebo with a prolonged duration of action, predictable kinetics, and an acceptable side effect profile. However, more adequately powered trials are needed to establish its superiority over plain bupivacaine.Keywords: liposomal bupivacaine, postoperative pain, pharmacokinetics, pharmacodynamics, efficacy, safety

  19. Engineering liposomal nanoparticles for targeted gene therapy.

    Science.gov (United States)

    Zylberberg, C; Gaskill, K; Pasley, S; Matosevic, S

    2017-08-01

    Recent mechanistic studies have attempted to deepen our understanding of the process by which liposome-mediated delivery of genetic material occurs. Understanding the interactions between lipid nanoparticles and cells is still largely elusive. Liposome-mediated delivery of genetic material faces systemic obstacles alongside entry into the cell, endosomal escape, lysosomal degradation and nuclear uptake. Rational design approaches for targeted delivery have been developed to reduce off-target effects and enhance transfection. These strategies, which have included the modification of lipid nanoparticles with target-specific ligands to enhance intracellular uptake, have shown significant promise at the proof-of-concept stage. Control of physical and chemical specifications of liposome composition, which includes lipid-to-DNA charge, size, presence of ester bonds, chain length and nature of ligand complexation, is integral to the performance of targeted liposomes as genetic delivery agents. Clinical advances are expected to rely on such systems in the therapeutic application of liposome nanoparticle-based gene therapy. Here, we discuss the latest breakthroughs in the development of targeted liposome-based agents for the delivery of genetic material, paying particular attention to new ligand and cationic lipid design as well as recent in vivo advances.

  20. Application of Ulex europaeus agglutinin I-modified liposomes for oral vaccine: Ex Vivo bioadhesion and in Vivo immunity.

    Science.gov (United States)

    Li, KeXin; Zhao, Xiuli; Xu, Shiyi; Pang, DaHai; Yang, ChunRong; Chen, DaWei

    2011-01-01

    The conjugation of Ulex europaeus agglutinin I (UEAI) onto surface of liposomes has been demonstrated to effectively improve the intestinal absorption of antigen, subsequently induced strong mucosal and systemic immune responses. In this context, we prepared bovine serum albumin (BSA)-encapsulating UEAI-modified liposomes (UEAI-LIP) and unmodified ones (LIP). The specific bioadhesion on mice gastro-intestinal mucosa was studied ex vivo. An important increase of interaction between UEAI-conjugated liposomes and the intestinal segments with Peyer's Patches (PPs) was observed compared with the unconjugated one (p<0.01). However, under the presence of α-L-fucose, which is the reported specific sugar for UEAI, specifically inhibited the activity of these conjugates. The immune-stimulating activity in vivo was studied by measuring immunoglobulin G (IgG) levels in serum and immunoglobulin A (IgA) levels in intestinal mucosal secretions following oral administration of BSA solution, LIP and UEAI-LIP in mice. Results indicate that antigen encapsulated in liposomes, especially the UEAI-modified ones, was favorable for inducing immune response. At 42 d after the first immunization, the highest IgG and IgA antibody levels produced by UEAI-LIP occurred, respectively showing 4.4-fold and 5-fold higher levels compared to those of the groups receiving BSA alone. This data demonstrated high potential of UEAI-modified liposomes for their use as carrier for oral vaccines.

  1. Preparation and Characterization of Naringenin-Loaded Elastic Liposomes for Topical Application.

    Directory of Open Access Journals (Sweden)

    Ming-Jun Tsai

    Full Text Available Excessive production of radical oxygen species in skin is a contributor to a variety of skin pathologies. Naringenin is a potent antioxidant. The purpose of the present study was to develop elastic liposomes for naringenin topical application. Naringenin-loaded elastic liposomes containing different amounts of Tween 80 and cholesterol were prepared. The physicochemical properties including vesicle size, surface charge, encapsulation efficiency, and permeability capacity were determined to evaluate the effect of components. The stability of formulation and skin irritation caused by drug-loaded elastic liposomes were also evaluated for assessment of the clinical utility of elastic liposomes. Saturated aqueous solution of naringenin and naringenin dissolved in 10% Tween 80 solution (5 mg/mL were used as the control group. The result showed that in using elastic liposomes as carrier, the deposition amounts in the skin of naringenin were significantly increased about 7.3~11.8-fold and 1.2~1.9-fold respectively, when compared with the saturated aqueous solution and Tween 80 solution-treated groups. The level of drug was more than 98.89±3.90% after 3 months of storage at 4℃. In a skin irritation test, the result showed experimental formulation exhibit considerably less irritating than the positive control (paraformaldehyde-treated group, suggesting its potential therapeutic application.

  2. Effects of Polyethylene Glycol Spacer Length and Ligand Density on Folate Receptor Targeting of Liposomal Doxorubicin In Vitro

    Directory of Open Access Journals (Sweden)

    Kumi Kawano

    2011-01-01

    Full Text Available The folate receptor is an attractive target for selective tumor delivery of liposomal doxorubicin (DXR because it is abundantly expressed in a large percentage of tumors. This study examined the effect of polyethylene glycol (PEG spacer length and folate ligand density on the targeting ability of folate-modified liposomes. Liposomes were modified with folate-derivatized PEG-distearoylphosphatidylethanolamine with PEG molecular weights of 2000, 3400, or 5000. The association of DXR-loaded liposomes with KB cells, which overexpress the folate receptor, was evaluated by flow cytometry at various ratios of folate modification. A low ratio of folate modification with a sufficiently long PEG chain showed the highest folate receptor-mediated association with the cells, but did not show the highest in vitro cytotoxicity. DXR release from folate-modified liposomes in endosomes might be different. These findings will be useful for designing folate receptor-targeting carriers.

  3. Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats

    Directory of Open Access Journals (Sweden)

    Campos-Martorell M

    2016-06-01

    Full Text Available Mireia Campos-Martorell,1 Mary Cano-Sarabia,2 Alba Simats,1 Mar Hernández-Guillamon,1 Anna Rosell,1 Daniel Maspoch,2,3 Joan Montaner1,4 1Neurovascular Research Laboratory, Institut de Recerca Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, 2Catalan Institute of Nanoscience and Nanotechnology (ICN2, CSIC and The Barcelona Institute of Science and Technology, Universitat Autònoma de Barcelona, Barcelona, 3Institució Catalana de Recerca i Estudis Avançats (ICREA, 4Neurovascular Unit, Department of Neurology, Universitat Autònoma de Barcelona, Hospital Vall d’Hebron, Barcelona, Spain Background and aims: Although the beneficial effects of statins on stroke have been widely demonstrated both in experimental studies and in clinical trials, the aim of this study is to prepare and characterize a new liposomal delivery system that encapsulates simvastatin to improve its delivery into the brain. Materials and methods: In order to select the optimal liposome lipid composition with the highest capacity to reach the brain, male Wistar rats were submitted to sham or transitory middle cerebral arterial occlusion (MCAOt surgery and treated (intravenous [IV] with fluorescent-labeled liposomes with different net surface charges. Ninety minutes after the administration of liposomes, the brain, blood, liver, lungs, spleen, and kidneys were evaluated ex vivo using the Xenogen IVIS® Spectrum imaging system to detect the load of fluorescent liposomes. In a second substudy, simvastatin was assessed upon reaching the brain, comparing free and encapsulated simvastatin (IV administration. For this purpose, simvastatin levels in brain homogenates from sham or MCAOt rats at 2 hours or 4 hours after receiving the treatment were detected through ultra-high-protein liquid chromatography. Results: Whereas positively charged liposomes were not detected in brain or plasma 90 minutes after their administration, neutral and negatively charged liposomes

  4. Photophysical studies of zinc phthalocyanine and chloroaluminum phthalocyanine incorporated into liposomes in the presence of additives

    Directory of Open Access Journals (Sweden)

    S.M.T. Nunes

    2004-02-01

    Full Text Available The photophysical properties of zinc phthalocyanine (ZnPC and chloroaluminum phthalocyanine (AlPHCl incorporated into liposomes of dimyristoyl phosphatidylcholine in the presence and absence of additives such as cholesterol or cardiolipin were studied by time-resolved fluorescence, laser flash photolysis and steady-state techniques. The absorbance of the drugs changed linearly with drug concentration, at least up to 5.0 µM in homogeneous and heterogeneous media, indicating that aggregation did not occur in these media within this concentration range. The incorporation of the drugs into liposomes increases the dimerization constant by one order of magnitude (for ZnPC, 3.6 x 10(4 to 1.0 x 10(5 M-1 and for AlPHCl, 3.7 x 10(4 to 1.5 x 10(5 M-1, but this feature dose does not rule out the use of this carrier, since the incorporation of these hydrophobic drugs into liposomes permits their systemic administration. Probe location in biological membranes and predominant positions of the phthalocyanines in liposomes were inferred on the basis of their fluorescence and triplet state properties. Both phthalocyanines are preferentially distributed in the internal regions of the liposome bilayer. The additives affect the distribution of these drugs within the liposomes, a fact that controls their delivery when both are used in a biological medium, retarding their release. The addition of the additives to the liposomes increases the internalization of phthalocyanines. The interaction of the drugs with a plasma protein, bovine serum albumin, was examined quantitatively by the fluorescence technique. The results show that when the drugs were incorporated into small unilamellar liposomes, the association with albumin was enhanced when compared with organic media, a fact that should increase the selectivity of tumor targeting by these phthalocyanines (for ZnPC, 0.71 x 10(6 to 1.30 x 10(7 M-1 and for AlPHCl, 4.86 x 10(7 to 3.10 x 10(8 M-1.

  5. Barriers to Liposomal Gene Delivery: from Application Site to the Target.

    Science.gov (United States)

    Saffari, Mostafa; Moghimi, Hamid Reza; Dass, Crispin R

    2016-01-01

    Gene therapy is a therapeutic approach to deliver genetic material into cells to alter their function in entire organism. One promising form of gene delivery system (DDS) is liposomes. The success of liposome-mediated gene delivery is a multifactorial issue and well-designed liposomal systems might lead to optimized gene transfection particularly in vivo. Liposomal gene delivery systems face different barriers from their site of application to their target, which is inside the cells. These barriers include presystemic obstacles (epithelial barriers), systemic barriers in blood circulation and cellular barriers. Epithelial barriers differ depending on the route of administration. Systemic barriers include enzymatic degradation, binding and opsonisation. Both of these barriers can act as limiting hurdles that genetic material and their vector should overcome before reaching the cells. Finally liposomes should overcome cellular barriers that include cell entrance, endosomal escape and nuclear uptake. These barriers and their impact on liposomal gene delivery will be discussed in this review.

  6. Liposomal curcumin and its application in cancer

    Directory of Open Access Journals (Sweden)

    Feng T

    2017-08-01

    Full Text Available Ting Feng,1,* Yumeng Wei,1,* Robert J Lee,2 Ling Zhao1 1Department of Pharmaceutics, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA *These authors contributed equally to this work Abstract: Curcumin (CUR is a yellow polyphenolic compound derived from the plant turmeric. It is widely used to treat many types of diseases, including cancers such as those of lung, cervices, prostate, breast, bone and liver. However, its effectiveness has been limited due to poor aqueous solubility, low bioavailability and rapid metabolism and systemic elimination. To solve these problems, researchers have tried to explore novel drug delivery systems such as liposomes, solid dispersion, microemulsion, micelles, nanogels and dendrimers. Among these, liposomes have been the most extensively studied. Liposomal CUR formulation has greater growth inhibitory and pro-apoptotic effects on cancer cells. This review mainly focuses on the preparation of liposomes containing CUR and its use in cancer therapy. Keywords: curcumin, liposomes, drug delivery, bioavailability, cancer 

  7. Nanoparticle-stabilized liposomes for pH-responsive gastric drug delivery.

    Science.gov (United States)

    Thamphiwatana, Soracha; Fu, Victoria; Zhu, Jingying; Lu, Diannan; Gao, Weiwei; Zhang, Liangfang

    2013-10-01

    We report a novel pH-responsive gold nanoparticle-stabilized liposome system for gastric antimicrobial delivery. By adsorbing small chitosan-modified gold nanoparticles (diameter ~10 nm) onto the outer surface of negatively charged phospholipid liposomes (diameter ~75 nm), we show that at gastric pH the liposomes have excellent stability with limited fusion ability and negligible cargo releases. However, when the stabilized liposomes are present in an environment with neutral pH, the gold stabilizers detach from the liposomes, resulting in free liposomes that can actively fuse with bacterial membranes. Using Helicobacter pylori as a model bacterium and doxycycline as a model antibiotic, we demonstrate such pH-responsive fusion activity and drug release profile of the nanoparticle-stabilized liposomes. Particularly, at neutral pH the gold nanoparticles detach, and thus the doxycycline-loaded liposomes rapidly fuse with bacteria and cause superior bactericidal efficacy as compared to the free doxycycline counterpart. Our results suggest that the reported liposome system holds a substantial potential for gastric drug delivery; it remains inactive (stable) in the stomach lumen but actively interacts with bacteria once it reaches the mucus layer of the stomach where the bacteria may reside.

  8. Multiseed liposomal drug delivery system using micelle gradient as driving force to improve amphiphilic drug retention and its anti-tumor efficacy.

    Science.gov (United States)

    Zhang, Wenli; Li, Caibin; Jin, Ya; Liu, Xinyue; Wang, Zhiyu; Shaw, John P; Baguley, Bruce C; Wu, Zimei; Liu, Jianping

    2018-11-01

    To improve drug retention in carriers for amphiphilic asulacrine (ASL), a novel active loading method using micelle gradient was developed to fabricate the ASL-loaded multiseed liposomes (ASL-ML). The empty ML were prepared by hydrating a thin film with empty micelles. Then the micelles in liposomal compartment acting as 'micelle pool' drove the drug to be loaded after the outer micelles were removed. Some reasoning studies including critical micelle concentration (CMC) determination, influencing factors tests on entrapment efficiency (EE), structure visualization, and drug release were carried out to explore the mechanism of active loading, ASL location, and the structure of ASL-ML. Comparisons were made between pre-loading and active loading method. Finally, the extended drug retention capacity of ML was evaluated through pharmacokinetic, drug tissue irritancy, and in vivo anti-tumor activity studies. Comprehensive results from fluorescent and transmission electron microscope (TEM) observation, encapsulation efficiency (EE) comparison, and release studies demonstrated the formation of ML-shell structure for ASL-ML without inter-carrier fusion. The location of drug mainly in inner micelles as well as the superiority of post-loading to the pre-loading method , in which drug in micelles shifted onto the bilayer membrane was an additional positive of this delivery system. It was observed that the drug amphiphilicity and interaction of micelles with drug were the two prerequisites for this active loading method. The extended retention capacity of ML has been verified through the prolonged half-life, reduced paw-lick responses in rats, and enhanced tumor inhibition in model mice. In conclusion, ASL-ML prepared by active loading method can effectively load drug into micelles with expected structure and improve drug retention.

  9. In vivo and in vitro evaluation of octyl methoxycinnamate liposomes

    Directory of Open Access Journals (Sweden)

    de Carvalho Varjão Mota A

    2013-12-01

    the HET-CAM test, indicating good histocompatibility. The formulation containing liposome/OMC had a higher in vivo solar photoprotection factor, but did not show increased water resistance. Inclusion in liposomes was able to slow down the release of OMC from the formulation, with a lower steady-state flux (3.9 ± 0.33 µg/cm2/hour compared with the conventional formulation (6.3 ± 1.21 µg/cm2/hour. The stripping method showed increased uptake of OMC in the stratum corneum, giving an amount of 22.64 ± 7.55 µg/cm2 of OMC, which was higher than the amount found for the conventional formulation (14.57 ± 2.30 µg/cm2.Conclusion: These results indicate that liposomes are superior carriers for OMC, and confer greater safety and efficacy to sunscreen formulations.Keywords: sunscreen, liposome, tape stripping, technetium-99-m, lipase

  10. Thermosensitive liposomal drug delivery systems: state of the art review

    Directory of Open Access Journals (Sweden)

    Kneidl B

    2014-09-01

    Full Text Available Barbara Kneidl,1,2 Michael Peller,3 Gerhard Winter,2 Lars H Lindner,1 Martin Hossann11Department of Internal Medicine III, University Hospital Munich, 2Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, 3Institute for Clinical Radiology, University Hospital Munich, Ludwig-Maximilians University, Munich, GermanyAbstract: Thermosensitive liposomes are a promising tool for external targeting of drugs to solid tumors when used in combination with local hyperthermia or high intensity focused ultrasound. In vivo results have demonstrated strong evidence that external targeting is superior over passive targeting achieved by highly stable long-circulating drug formulations like PEGylated liposomal doxorubicin. Up to March 2014, the Web of Science listed 371 original papers in this field, with 45 in 2013 alone. Several formulations have been developed since 1978, with lysolipid-containing, low temperature-sensitive liposomes currently under clinical investigation. This review summarizes the historical development and effects of particular phospholipids and surfactants on the biophysical properties and in vivo efficacy of thermosensitive liposome formulations. Further, treatment strategies for solid tumors are discussed. Here we focus on temperature-triggered intravascular and interstitial drug release. Drug delivery guided by magnetic resonance imaging further adds the possibility of performing online monitoring of a heating focus to calculate locally released drug concentrations and to externally control drug release by steering the heating volume and power. The combination of external targeting with thermosensitive liposomes and magnetic resonance-guided drug delivery will be the unique characteristic of this nanotechnology approach in medicine.Keywords: thermosensitive liposomes, phosphatidyloligoglycerol, hyperthermia, high intensity focused ultrasound, drug delivery, drug targeting

  11. Aerosolized liposomes with dipalmitoyl phosphatidylcholine enhance pulmonary insulin delivery.

    Science.gov (United States)

    Chono, Sumio; Fukuchi, Rie; Seki, Toshinobu; Morimoto, Kazuhiro

    2009-07-20

    The pulmonary insulin delivery characteristics of liposomes were examined. Aerosolized liposomes containing insulin were administered into rat lungs and the enhancing effect on insulin delivery was evaluated by changes of plasma glucose levels. Liposomes with dipalmitoyl phosphatidylcholine (DPPC) enhanced pulmonary insulin delivery in rats, however, liposomes with dilauroyl, dimyristoyl, distearoyl or dioleoyl phosphatidylcholine did not. Liposomes with DPPC also enhanced the in vitro permeation of FITC dextran (Mw 4400, FD-4) through the calu-3 cell monolayer by reducing the transepithelial electrical resistance and did not harm lung tissues in rats. These findings suggest that liposomes with DPPC enhance pulmonary insulin delivery by opening the epithelial cell space in the pulmonary mucosa not mucosal cell damage. Liposomes with DPPC could be useful as a pulmonary delivery system for peptide and protein drugs.

  12. A safe and efficient hepatocyte-selective carrier system based on myristoylated preS1/21-47 domain of hepatitis B virus

    Science.gov (United States)

    Zhang, Quan; Zhang, Xuanmiao; Chen, Tijia; Wang, Xinyi; Fu, Yao; Jin, Yun; Sun, Xun; Gong, Tao; Zhang, Zhirong

    2015-05-01

    A safe and efficient liver targeted PEGylated liposome (PEG-Lip) based on N-terminal myristoylated preS1/21-47 (preS1/21-47myr) of hepatitis B virus was successfully developed. The study aimed to elucidate the cellular uptake mechanism of preS1/21-47myr modified PEG-Lip (preS1/21-47myr-PEG-Lip) in hepatogenic cells and the distribution behavior of preS1/21-47myr-PEG-Lip in Vr:CD1 (ICR) mice. The cellular uptake results showed that preS1/21-47myr-PEG-Lip was effectively taken up by hepatogenic cells (including primary hepatocytes and liver tumor cells) through a receptor-mediated endocytosis pathway compared with non-hepatogenic cells. After systemic administration to H22 hepatoma-bearing mice, preS1/21-47myr-PEG-Lip showed significant liver-specific delivery and an increase in the distribution of preS1/21-47myr-PEG-Lip in hepatic tumor. Furthermore, the antitumor effect of preS1/21-47myr-PEG-Lip loaded with paclitaxel (PTX) was remarkably stronger than that of PTX injection and PTX loaded liposomes (including common liposomes and PEG-Lip). In safety evaluation, no acute systemic toxicity and immunotoxicity were observed after intravenous injection of preS1/21-47myr-PEG-Lip. No liver toxicity was observed despite the dramatic increase of preS1/21-47myr-PEG-Lip in liver. Taken together, preS1/21-47myr-PEG-Lip represents a promising carrier system for targeted liver disease therapy and imaging.

  13. Liposome-encapsulated chemotherapy

    DEFF Research Database (Denmark)

    Børresen, B.; Hansen, A. E.; Kjær, A.

    2018-01-01

    Cytotoxic drugs encapsulated into liposomes were originally designed to increase the anticancer response, while minimizing off-target adverse effects. The first liposomal chemotherapeutic drug was approved for use in humans more than 20years ago, and the first publication regarding its use...... to inherent issues with the enhanced permeability and retention effect, the tumour phenomenon which liposomal drugs exploit. This effect seems very heterogeneously distributed in the tumour. Also, it is potentially not as ubiquitously occurring as once thought, and it may prove important to select patients...... not resolve the other challenges that liposomal chemotherapy faces, and more work still needs to be done to determine which veterinary patients may benefit the most from liposomal chemotherapy....

  14. Development of liposomes entrapped in alginate beads for the treatment of colorectal cancer.

    Science.gov (United States)

    Bansal, Divya; Gulbake, Arvind; Tiwari, Jyoti; Jain, Sanjay K

    2016-01-01

    Folic Acid conjugated liposomes encapsulating Oxaliplatin (L-OHP) were entrapped in alginate beads and further coated with Eudragit-S-100 for effective delivery to colon tumors. Liposomes were prepared by cast film method and folic acid was coupled on the surface of liposomes. They were further entrapped in alginate beads which were Eudragit coated for degradation in the colonic region. The prepared beads were characterized for shape and surface morphology, percentage entrapment efficiency and drug release studies. The in vitro drug release was investigated using a USP dissolution paddle type apparatus in different simulated gastrointestinal fluids. In vivo studies of the beads containing free drug, folic acid coupled and uncoupled liposomes bearing L-OHP was administered orally at the dose of 10mg L-OHP/kg body weight to tumor bearing NUDE/SCID mice. γ-Scintigraphic study showed that Eudragit coated alginate beads entered into the colon of Balb/c mice between 4.20 and 4.50h after oral administration. In vivo data showed that folic acid coupled liposomes entrapped in alginate beads delivered 2.82 ± 0.58 and 21.52 ± 2.76 μg L-OHP/g tissues in the colon and tumor after 12h, reflecting its targeting potential to colon and tumor. The results clearly demonstrate that Eudragit coated calcium alginate beads bearing folic acid coupled liposome can be used as a prospective carrier for drug delivery to colon specific tumor. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Legionella pneumophila secretes a mitochondrial carrier protein during infection.

    Directory of Open Access Journals (Sweden)

    Pavel Dolezal

    2012-01-01

    Full Text Available The Mitochondrial Carrier Family (MCF is a signature group of integral membrane proteins that transport metabolites across the mitochondrial inner membrane in eukaryotes. MCF proteins are characterized by six transmembrane segments that assemble to form a highly-selective channel for metabolite transport. We discovered a novel MCF member, termed Legionellanucleotide carrier Protein (LncP, encoded in the genome of Legionella pneumophila, the causative agent of Legionnaire's disease. LncP was secreted via the bacterial Dot/Icm type IV secretion system into macrophages and assembled in the mitochondrial inner membrane. In a yeast cellular system, LncP induced a dominant-negative phenotype that was rescued by deleting an endogenous ATP carrier. Substrate transport studies on purified LncP reconstituted in liposomes revealed that it catalyzes unidirectional transport and exchange of ATP transport across membranes, thereby supporting a role for LncP as an ATP transporter. A hidden Markov model revealed further MCF proteins in the intracellular pathogens, Legionella longbeachae and Neorickettsia sennetsu, thereby challenging the notion that MCF proteins exist exclusively in eukaryotic organisms.

  16. Structural properties of liposomes from digital holographic microscopy

    Science.gov (United States)

    Di Maio, Isabelle L.; Carl, Daniel; Langehanenberg, Patrik; Valenzuela, Stella M.; Battle, Andrew R.; Al Khazaaly, Sabah; Killingsworth, Murray; Kemper, Bjorn; von Bally, Gert; Martin, Donald K.

    2006-01-01

    We have constructed liposomes from L alpha Phosphatidylcholine (PC) lipids, which are biomimetic lipids similar to those present in the membranes of mammalian cells. We propose an advance in the use of liposomes, such as for drug delivery, to incorporate into the liposomal membranes transport proteins that have been extracted from the lipid membranes of mammalian cells. In this paper, we describe the usage of a novel optical microscope to characterize the nanomechanical properties of these liposomes. We have applied the technique of digital holographic microscopy, using an instrument recently developed at the University of Münster, Germany. This system enabled us to measure quantitatively the structural changes in liposomes. We have investigated the deformations of these biomimetic lipids comprising these liposomes by applying osmotic stresses, in order to gain insight into the membrane environment prior to incorporation of cloned membrane transport proteins. This control of the nanomechanical properties is important in the stresses transmitted to mechanosensitive ion channels that we have incorporated into the liposomal membranes. These liposomes provide transporting vesicles that respond to mechanical stresses, such as those that occur during implantation.

  17. Shotgun proteomic analytical approach for studying proteins adsorbed onto liposome surface

    KAUST Repository

    Capriotti, Anna Laura

    2011-07-02

    The knowledge about the interaction between plasma proteins and nanocarriers employed for in vivo delivery is fundamental to understand their biodistribution. Protein adsorption onto nanoparticle surface (protein corona) is strongly affected by vector surface characteristics. In general, the primary interaction is thought to be electrostatic, thus surface charge of carrier is supposed to play a central role in protein adsorption. Because protein corona composition can be critical in modifying the interactive surface that is recognized by cells, characterizing its formation onto lipid particles may serve as a fundamental predictive model for the in vivo efficiency of a lipidic vector. In the present work, protein coronas adsorbed onto three differently charged cationic liposome formulations were compared by a shotgun proteomic approach based on nano-liquid chromatography-high-resolution mass spectrometry. About 130 proteins were identified in each corona, with only small differences between the different cationic liposome formulations. However, this study could be useful for the future controlled design of colloidal drug carriers and possibly in the controlled creation of biocompatible surfaces of other devices that come into contact with proteins into body fluids. © 2011 Springer-Verlag.

  18. A targeted liposome delivery system for combretastatin A4: formulation optimization through drug loading and in vitro release studies.

    Science.gov (United States)

    Nallamothu, Ramakrishna; Wood, George C; Kiani, Mohammad F; Moore, Bob M; Horton, Frank P; Thoma, Laura A

    2006-01-01

    Efficient liposomal therapeutics require high drug loading and low leakage. The objective of this study is to develop a targeted liposome delivery system for combretastatin A4 (CA4), a novel antivascular agent, with high loading and stable drug encapsulation. Liposomes composed of hydrogenated soybean phosphatidylcholine (HSPC), cholesterol, and distearoyl phosphoethanolamine-PEG-2000 conjugate (DSPE-PEG) were prepared by the lipid film hydration and extrusion process. Cyclic arginine-glycine-aspartic acid (RGD) peptides with affinity for alphav beta3-integrins overexpressed on tumor vascular endothelial cells were coupled to the distal end of polyethylene glycol (PEG) on the liposomes sterically stabilized with PEG (non-targeted liposomes; LCLs). Effect of lipid concentration, drug-to-lipid ratio, cholesterol, and DSPE-PEG content in the formulation on CA4 loading and its release from the liposomes was studied. Total liposomal CA4 levels obtained increased with increasing lipid concentration in the formulation. As the drug-to-lipid ratio increased from 10:100 to 20:100, total drug in the liposome formulation increased from 1.05+/-0.11 mg/mL to 1.55+/-0.13 mg/mL, respectively. When the drug-to-lipid ratio was further raised to 40:100, the total drug in liposome formulation did not increase, but the amount of free drug increased significantly, thereby decreasing the percent of entrapped drug. Increasing cholesterol content in the formulation decreased drug loading. In vitro drug leakage from the liposomes increased with increase in drug-to-lipid ratio or DSPE-PEG content in the formulation; whereas increasing cholesterol content of the formulation up to 30 mol-percent, decreased CA4 leakage from the liposomes. Ligand coupling to the liposome surface increased drug leakage as a function of ligand density. Optimized liposome formulation with 100 mM lipid concentration, 20:100 drug-to-lipid ratio, 30 mol-percent cholesterol, 4 mol-percent DSPE-PEG, and 1 mol

  19. Specific interaction of central nervous system myelin basic protein with lipids effects of basic protein on glucose leakage from liposomes

    NARCIS (Netherlands)

    Gould, R.M.; London, Y.

    1972-01-01

    The leakage from liposomes preloaded with glucose was continuously monitored in a Perkin-Elmer Model 356 dual beam spectrophotometer using an enzyme-linked assay system. The central nervous system myelin basic protein (A1 protein) caused a 3–4-fold increase in the rate of leakage from liposomes

  20. In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Gu MJ

    2015-08-01

    Full Text Available Meng-Jie Gu,1,* Kun-Feng Li,1,* Lan-Xin Zhang,1 Huan Wang,1 Li-Si Liu,2 Zhuo-Zhao Zheng,2 Nan-Yin Han,1 Zhen-Jun Yang,1 Tian-Yuan Fan1 1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 2Department of Radiology, Peking University Third Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Novel gadolinium-loaded liposomes guided by GBI-10 aptamer were developed and evaluated in vitro to enhance magnetic resonance imaging (MRI diagnosis of tumor. Nontargeted gadolinium-loaded liposomes were achieved by incorporating amphipathic material, Gd (III [N,N-bis-stearylamidomethyl-N'-amidomethyl] diethylenetriamine tetraacetic acid, into the liposome membrane using lipid film hydration method. GBI-10, as the targeting ligand, was then conjugated onto the liposome surface to get GBI-10-targeted gadolinium-loaded liposomes (GTLs. Both nontargeted gadolinium-loaded liposomes and GTLs displayed good dispersion stability, optimal size, and zeta potential for tumor targeting, as well as favorable imaging properties with enhanced relaxivity compared with a commercial MRI contrast agent (CA, gadopentetate dimeglumine. The use of GBI-10 aptamer in this liposomal system was intended to result in increased accumulation of gadolinium at the periphery of C6 glioma cells, where the targeting extracellular matrix protein tenascin-C is overexpressed. Increased cellular binding of GTLs to C6 cells was confirmed by confocal microscopy, flow cytometry, and MRI, demonstrating the promise of this novel delivery system as a carrier of MRI contrast agent for the diagnosis of tumor. These studies provide a new strategy furthering the development of nanomedicine for both diagnosis and therapy of tumor. Keywords: magnetic resonance imaging, gadolinium, liposomes, tenascin-C, GBI-10 aptamer, tumor targeting

  1. Bleomycin-Loaded pH-Sensitive Polymer–Lipid-Incorporated Liposomes for Cancer Chemotherapy

    Directory of Open Access Journals (Sweden)

    Eiji Yuba

    2018-01-01

    Full Text Available Cancer chemotherapeutic systems with high antitumor effects and less adverse effects are eagerly desired. Here, a pH-sensitive delivery system for bleomycin (BLM was developed using egg yolk phosphatidylcholine liposomes modified with poly(ethylene glycol-lipid (PEG-PE for long circulation in the bloodstream and 2-carboxycyclohexane-1-carboxylated polyglycidol-having distearoyl phosphatidylethanolamine (CHexPG-PE for pH sensitization. The PEG-PE/CHexPG-PE-introduced liposomes showed content release responding to pH decrease and were taken up by tumor cells at a rate 2.5 times higher than that of liposomes without CHexPG-PE. BLM-loaded PEG-PE/CHexPG-PE-introduced liposomes exhibited comparable cytotoxicity with that of the free drug. Intravenous administration of these liposomes suppressed tumor growth more effectively in tumor-bearing mice than did the free drug and liposomes without CHexPG-PE. However, at a high dosage of BLM, these liposomes showed severe toxicity to the spleen, liver, and lungs, indicating the trapping of liposomes by mononuclear phagocyte systems, probably because of recognition of the carboxylates on the liposomes. An increase in PEG molecular weight on the liposome surface significantly decreased toxicity to the liver and spleen, although toxicity to the lungs remained. Further improvements such as the optimization of PEG density and lipid composition and the introduction of targeting ligands to the liposomes are required to increase therapeutic effects and to reduce adverse effects.

  2. A systemic administration of liposomal curcumin inhibits radiation pneumonitis and sensitizes lung carcinoma to radiation

    Directory of Open Access Journals (Sweden)

    Shi HS

    2012-05-01

    Full Text Available Hua-shan Shi1,* Xiang Gao,1,3,* Dan Li,1,* Qiong-wen Zhang,1 Yong-sheng Wang,2 Yu Zheng,1 Lu-Lu Cai,1 Ren-ming Zhong,2 Ao Rui,1 Zhi-yong Li,1 Hao Zheng,1 Xian-cheng Chen,1 Li-juan Chen,11State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medicine School, Sichuan University, Chengdu, Sichuan, People's Republic of China; 2State Key Laboratory of Biotherapy and Department of Thoracic Oncology, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China; 3Deparment of Pathophysiology, College of Preclinical and Forensic Medical Sciences, Sichuan University, Chengdu, People's Republic of China*These authors contributed equally to this workAbstract: Radiation pneumonitis (RP is an important dose-limiting toxicity during thoracic radiotherapy. Previous investigations have shown that curcumin is used for the treatment of inflammatory conditions and cancer, suggesting that curcumin may prevent RP and sensitize cancer cells to irradiation. However, the clinical advancement of curcumin is limited by its poor water solubility and low bioavailability after oral administration. Here, a water-soluble liposomal curcumin system was developed to investigate its prevention and sensitizing effects by an intravenous administration manner in mice models. The results showed that liposomal curcumin inhibited nuclear factor-κB pathway and downregulated inflammatory factors including tumor necrosis factor-α, interleukin (IL-6, IL-8, and transforming growth factor-β induced by thoracic irradiation. Furthermore, the combined treatment with liposomal curcumin and radiotherapy increased intratumoral apoptosis and microvessel responses to irradiation in vivo. The significantly enhanced inhibition of tumor growth also was observed in a murine lung carcinoma (LL/2 model. There were no obvious toxicities observed in mice. The current results indicate that liposomal curcumin can effectively

  3. Exploring the fate of liposomes in the intestine by dynamic in vitro lipolysis

    DEFF Research Database (Denmark)

    Parmentier, Johannes; Thomas, Nicky; Müllertz, Anette

    2012-01-01

    precipitation was detected during the lipolysis assay, despite pronounced lipolytic degradation and change in vesicle size. In conclusion, the tested dynamic in vitro lipolysis model is suitable for the assessment of liposome stability in the intestine. Furthermore, liposomes might be a useful alternative......Liposomes are generally well tolerated drug delivery systems with a potential use for the oral route. However, little is known about the fate of liposomes during exposure to the conditions in the gastro-intestinal tract (GIT). To gain a better understanding of liposome stability in the intestine......, a dynamic in vitro lipolysis model, which so far has only been used for the in vitro characterisation of other lipid-based drug delivery systems, was applied to different liposomal formulations. Liposome size and phospholipid (PL) digestion were determined as two markers for liposome stability. In addition...

  4. Low-complexity Joint Sub-carrier Phase Noise Compensation for Digital Multi-carrier Systems

    DEFF Research Database (Denmark)

    Yankov, Metodi Plamenov; Barletta, Luca; Zibar, Darko

    2017-01-01

    Joint sub-carrier phase noise processing is proposed which recovers the SNR penalty related to decreased sub-carrier baudrate w.r.t. single carrier systems. The method enables digital sub-banding to be safely employed for nonlinear mitigation for modulation formats of up to 256-QAM.......Joint sub-carrier phase noise processing is proposed which recovers the SNR penalty related to decreased sub-carrier baudrate w.r.t. single carrier systems. The method enables digital sub-banding to be safely employed for nonlinear mitigation for modulation formats of up to 256-QAM....

  5. Resolution V fractional factorial Design for Screening of factors affecting weakly basic drugs liposomal systems.

    Science.gov (United States)

    El-Helaly, Sara Nageeb; Habib, Basant A; Abd El-Rahman, Mohamed K

    2018-04-21

    This study aims to investigate factors affecting weakly basic drugs liposomal systems. Resolution V fractional factorial design (2 V 5-1 ) is used as an example of screening designs that would better be used as a wise step before proceeding with detailed factors effects or optimization studies. Five factors probable to affect liposomal systems of weakly basic drugs were investigated using Amisulpride as a model drug. Factors studied were; A: Preparation technique B: Phosphatidyl choline (PhC) amount (mg) C: Cholesterol: PhC molar ratio, D: Hydration volume (ml) and E: Sonication type. Levels investigated were; Ammonium sulphate-pH gradient technique or Transmembrane zinc chelation-pH gradient technique, 200 or 400 mg, 0 or 0.5, 10 or 20 ml and bath or probe sonication for A, B, C, D and E respectively. Responses measured were Particle size (PS) (nm), Zeta potential (ZP) (mV) and Entrapment efficiency percent (EE%). Ion selective electrode was used as a novel method for measuring unentrapped drug concentration and calculating entrapment efficiency without the need for liposomal separation. Factors mainly affecting the studied responses were Cholesterol: PhC ratio and hydration volume for PS, preparation technique for ZP and preparation technique and hydration volume for EE%. The applied 2 V 5-1 design enabled the use of only 16 trial combinations for screening the influence of five factors on weakly basic drugs liposomal systems. This clarifies the value of the use of screening experiments before extensive investigation of certain factors in detailed optimization studies. Copyright © 2017. Published by Elsevier B.V.

  6. Directed Evolution of Proteins through In Vitro Protein Synthesis in Liposomes

    Directory of Open Access Journals (Sweden)

    Takehiro Nishikawa

    2012-01-01

    Full Text Available Directed evolution of proteins is a technique used to modify protein functions through “Darwinian selection.” In vitro compartmentalization (IVC is an in vitro gene screening system for directed evolution of proteins. IVC establishes the link between genetic information (genotype and the protein translated from the information (phenotype, which is essential for all directed evolution methods, by encapsulating both in a nonliving microcompartment. Herein, we introduce a new liposome-based IVC system consisting of a liposome, the protein synthesis using recombinant elements (PURE system and a fluorescence-activated cell sorter (FACS used as a microcompartment, in vitro protein synthesis system, and high-throughput screen, respectively. Liposome-based IVC is characterized by in vitro protein synthesis from a single copy of a gene in a cell-sized unilamellar liposome and quantitative functional evaluation of the synthesized proteins. Examples of liposome-based IVC for screening proteins such as GFP and β-glucuronidase are described. We discuss the future directions for this method and its applications.

  7. Antitumor activity of intratracheal inhalation of temozolomide (TMZ) loaded into gold nanoparticles and/or liposomes against urethane-induced lung cancer in BALB/c mice.

    Science.gov (United States)

    Hamzawy, Mohamed A; Abo-Youssef, Amira M; Salem, Heba F; Mohammed, Sameh A

    2017-11-01

    The current study aimed to develop gold nanoparticles (GNPs) and liposome-embedded gold nanoparticles (LGNPs) as drug carriers for temozolomide (TMZ) and investigate the possible therapeutic effects of intratracheal inhalation of nanoformulation of TMZ-loaded gold nanoparticles (TGNPs) and liposome-embedded TGNPs (LTGNPs) against urethane-induced lung cancer in BALB/c mice. Physicochemical characters and zeta potential studies for gold nanoparticles (GNPs) and liposome-embedded gold nanoparticles (LGNPs) were performed. The current study was conducted by inducing lung cancer chemically via repeated exposure to urethane in BALB/C mice. GNPs and LGNPs were exhibited in uniform spherical shape with adequate dispersion stability. GNPs and LGNPs showed no significant changes in comparison to control group with high safety profile, while TGNPs and LTGNPs succeed to improve all biochemical data and histological patterns. GNPs and LGNPs are promising drug carriers and succeeded in the delivery of small and efficient dose of temozolomide in treatment lung cancer. Antitumor activity was pronounced in animal-treated LTGNPs, these effects may be due to synergistic effects resulted from combination of temozolomide and gold nanoparticles and liposomes that may improve the drug distribution and penetration.

  8. Liposome fusion and lipid exchange on ultraviolet irradiation of liposomes containing a photochromic phospholipid

    International Nuclear Information System (INIS)

    Morgan, C.G.; Sandhu, S.S.; Mitchell, A.C.

    1995-01-01

    A photochromic phospholipid, 1,2-bis[4-n-butylphenylazo)phenylbutyroyl]phosphatidylcholine (Bis-Azo PC) has been incorporated inot liposomes of gel- and liquid-crystalline-phase phospholipids. Liposomes of gel-phase phospholipid are stable in the presence of the trans photostationary state Bis-Az0 PC and can encapsulate fluorescent marker dye. On photoisomerization to the cis photostationary state, trapped marker is rapidly released. Liposomes containing Bis-Azo PC can rapidly fuse together after UV isomerization, this process continuing in the dark. Exposure to white light causes reversion of Bis-Azo PC to the trans form and halts dye leakage and vesicle fusion. Both unilamellar and multilamellar liposomes are able to fuse together on UV exposure. On UV photolysis, liposomes containing Bis-Azo PC do not fuse with a large excess of unlabeled liposomes, but transfer of Bis-Azo PC can be demonstrated spectrophotometrically. Vesicles of pure gel-phase lipid containing trapped marker dye but initially no Bis-Azo PC become leaky as a result of this lipid transfer. Liposomes composed of liquid-crystalline-phase phosphatidylcholine-containing Bis-Azo PC neither leak trapped marker nor fuse together on photolysis, nor do liquid-crystalline-phase liposomes, fuse with gel-phase liposomes under these conditions. (Author)

  9. Presence of electrostatically adsorbed polysaccharides improves spray drying of liposomes.

    Science.gov (United States)

    Karadag, Ayse; Özçelik, Beraat; Sramek, Martin; Gibis, Monika; Kohlus, Reinhard; Weiss, Jochen

    2013-02-01

    Spray drying of liposomes with conventional wall materials such as maltodextrins often yields nonfunctional powders, that is, liposomes break down during drying and rehydration. Electrostatically coating the surface of liposomes with a charged polymer prior to spray drying may help solve this problem. Anionic lecithin liposomes (approximately 400 nm) were coated with lower (approximately 500 kDa, LMW-C) or higher (approximately 900 kDa, HMW-C) molecular weight cationic chitosan using the layer-by-layer depositing method. Low (DE20, LMW-MD) or high molecular weight (DE2, HMW-MD) maltodextrin was added as wall material to facilitate spray drying. If surfaces of liposomes (1%) were completely covered with chitosan (0.4%), no bridging or depletion flocculation would occur, and mean particle diameters would be approximately 500 nm. If maltodextrins (20%) were added to uncoated liposomes, extensive liposomal breakdown would occur making the system unsuitable for spray drying. No such aggregation or breakdown was observed when maltodextrin was added to chitosan-coated liposomes. Size changed little or even decreased slightly depending on the molecular weight of maltodextrin added. Scanning electron microscopy images of powders containing chitosan-coated liposomes revealed that their morphologies depended on the type of maltodextrin added. Powders prepared with LMW-MD contained mostly spherical particles while HMW-MD powders contained particles with concavities and dents. Upon redispersion, coated liposomes yielded back dispersions with particle size distributions similar to the original ones, except for LMW-C coated samples that had been spray dried with HMW-MD which yielded aggregates (approximately 30 μm). Results show that coating of liposomes with an absorbing polymer allows them to be spray dried with conventional maltodextrin wall materials. Liposomes have attracted considerable attention in the food and agricultural, biomedical industries for the delivery of

  10. Nanohybrid systems of non-ionic surfactant inserting liposomes loading paclitaxel for reversal of multidrug resistance.

    Science.gov (United States)

    Ji, Xiufeng; Gao, Yu; Chen, Lingli; Zhang, Zhiwen; Deng, Yihui; Li, Yaping

    2012-01-17

    Three new nanohybrid systems of non-ionic surfactant inserting liposomes loading paclitaxel (PTX) (NLPs) were prepared to overcome multidrug resistance (MDR) in PTX-resistance human lung cancer cell line. Three non-ionic surfactants, Solutol HS 15 (HS-15), pluronic F68 (PF-68) and cremophor EL (CrEL) were inserted into liposomes by film hydration method to form NLPs with an average size of around 110, 180 and 110 nm, respectively. There was an obvious increase of rhodamin 123 (Rh123) accumulation in A549/T cells after treated with nanohybrid systems loading Rh123 (NLRs) when compared with free Rh123 or liposomes loading Rh123 without surfactants (LRs), which indicated the significant inhibition effects of NLRs on drug efflux. The P-gp detection and ATP determination demonstrated that BNLs could not only interfere P-gp expression on the membrane of drug resistant cells, but also decrease ATP level in the cells. The cytotoxicity of NLPs against A549/T cells was higher than PTX loaded liposomes without surfactants (LPs), and the best result was achieved after treated with NLPs2. The apoptotic assay and the cell cycle analysis showed that NLPs could induce more apoptotic cells in drug resistant cells when compared with LPs. These results suggested that NLPs could overcome MDR by combination of drug delivery, P-gp inhibition and ATP depletion, and showed potential for treatment of MDR. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Bladder uptake of liposomes after intravesical administration occurs by endocytosis.

    Directory of Open Access Journals (Sweden)

    Bharathi Raja Rajaganapathy

    Full Text Available Liposomes have been used therapeutically and as a local drug delivery system in the bladder. However, the exact mechanism for the uptake of liposomes by bladder cells is unclear. In the present study, we investigated the role of endocytosis in the uptake of liposomes by cultured human UROtsa cells of urothelium and rat bladder. UROtsa cells were incubated in serum-free media with liposomes containing colloidal gold particles for 2 h either at 37°C or at 4°C. Transmission Electron Microscopy (TEM images of cells incubated at 37°C found endocytic vesicles containing gold inside the cells. In contrast, only extracellular binding was noticed in cells incubated with liposomes at 4°C. Absence of liposome internalization at 4°C indicates the need of energy dependent endocytosis as the primary mechanism of entry of liposomes into the urothelium. Flow cytometry analysis revealed that the uptake of liposomes at 37°C occurs via clathrin mediated endocytosis. Based on these observations, we propose that clathrin mediated endocytosis is the main route of entry for liposomes into the urothelial layer of the bladder and the findings here support the usefulness of liposomes in intravesical drug delivery.

  12. Enzyme sensitive liposomes in chemotherapy and potentiation of immunotherapy

    DEFF Research Database (Denmark)

    Østrem, Ragnhild Garborg

    efficacy and induction of severe adverse effects. Interestingly, the pharmacokinetics and biodistribution of drugs can be substantially altered by encapsulation in liposomal drug delivery vehicles. The first chapter of this thesis gives a brief introduction to cancer followed by a discussion...... of the applicability of liposomes as drug delivery vehicles in cancer therapy. The second chapter describes the development of a liposome system with an inbuilt release mechanism triggered by secretory phospholipase A2 (sPLA2). This enzyme is expressed at elevated levels in many human cancers, and as such represents...... with an introduction to the cancer-immunity cycle and to how treatment approaches can aid this interplay. Subsequently it demonstrates that the presence of a functional immune system is important in the efficacy of liposomal oxaliplatin, and that this efficacy can be substantially enhanced by combination with...

  13. Chemical meningitis related to intra-CSF liposomal cytarabine.

    Science.gov (United States)

    Durand, Bénédicte; Zairi, Fahed; Boulanger, Thomas; Bonneterre, Jacques; Mortier, Laurent; Le Rhun, Emilie

    2017-10-01

    Therapeutic options of leptomeningeal metastases include intra-cerebrospinal fluid (CSF) chemotherapy. Among intra-CSF agents, liposomal cytarabine has advantages but can induce specific toxicities. A BRAF-V600E-mutated melanoma leptomeningeal metastases patient, treated by dabrafenib and liposomal cytarabine, presented after the first injection of liposomal cytarabine with hyperthermia and headaches. Despite sterile CSF/blood analyses, extended intravenous antibiotics were given and the second injection was delayed. The diagnosis of chemical meningitis was finally made. Dose reduction and appropriate symptomatic treatment permitted the administration of 15 injections of liposomal cytarabine combined with dabrafenib. A confirmation of the diagnosis of chemical meningitis is essential in order (1) not to delay intra-CSF or systemic chemotherapy or (2) to limit the administration of unnecessary but potentially toxic antibiotics.

  14. Stabilization of liophilized liposomal products

    Directory of Open Access Journals (Sweden)

    2001-08-01

    Full Text Available Liposomes as a drug carrier have numerous dominancy. Liophilization is the most propr form of these products for long-term maintenance, but this procedure is affected by unstabilizing agent that results in destruction of membrane, release of content and change in size and microbial contamination; hence for prevention of the adverse effects, the protective role of sugars such as: Maltose, Fructose, Glucose, Galactose, Saccharose and Lactose were studied. For this purpose, after preparation of liposomal suspention, categorized in for duplicate groups and concentrations of 25, 50, 100 percent of these sugars were added to those. On the basis of color and consistency of products, the best method of freezing is as application of absolute alcohol and then chilling in-70 oc for 16 h. In survey of protective substances concentrations 0.7, 1.4, 2.8, and 5.6 percent of the mentioned sugars were used for calculating of leakage percent (Upon on the ratio of optical density of treated samples to untreated. In this study, released maltose had highest effect. Level of fusion and aggregation had any significant difference between pre and post lyophilized samples in centrifugation with 10000 rpm. Microbial state of recent samples were studied by culturing in SCD and SCDA media that indicated microbial growth in both samples.     

  15. Liposome distribution after intravenous and selective intraarterial infusion in dogs

    International Nuclear Information System (INIS)

    Wright, K.C.; Kasi, L.P.; Jahns, M.S.; Hashimoto, S.; Wallace, S.

    1990-01-01

    In an effort to improve hepatic uptake of liposomes for drug delivery, empty vesicles were administered by means of selective arterial infusion. Negatively charged, multilamellar liposomes were labeled with technetium-99m and infused into healthy adult dogs. Each dog received 100 mg/m2 of lipid over 10 minutes at 2 mL/min. Liposomes were administered via the common hepatic artery after proximal occlusion of the gastroduodenal artery, via the cranial mesenteric artery, and via the cephalic vein. Distribution (liver, spleen, and lungs) was determined by computer-assisted external imaging techniques. On the average, after arterial infusion, 69.2% of the total activity was located in the liver, 3.6% in the spleen, 3.2% in the lungs, and 3.5% in the general circulation. Following venous injection, 50.7% of the radioactivity was found in the liver, 9.1% in the spleen, 8.6% in the lungs, and 6.7% in the peripheral blood. Once the liposomes entered the systemic circulation, they were cleared at the same rate (half-life beta = 21.5 hours) independent of their route of administration. Increased hepatic liposome uptake should translate into higher local and lower systemic liposomal drug levels

  16. Kinetics of distribution and retention of /sup 3/H-oestradiol-17. beta. in rat tissues: a comparative study with free oestradiol and after its incorporation into liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Jehan, Q; Srivasta, S; Setty, B S [Central Drug Research Inst., Lucknow (India). Div. of Endocrinology; Akhlaq, M; Ahmad, A [Central Drug Research Inst., Lucknow (India)

    1982-01-01

    With a view to impart selective uptake of estrogen by the target tissues of rat, liposomes in which (6,7-/sup 3/H) estradiol-17..beta.. constituted a part of lipid bilayer were used as carriers of the hormone. The distribution and retention of the radioactivity was determined in blood plasma, uterus, liver, kidney, spleen and leg muscle of ovariectomized rat at different time intervals up to 72 hr following a single intravenous injection of free estradiol (1.61 ..mu..Ci) or an equivalent amount of liposomal estradiol. When free estradiol was administered, uterus showed peak amount of radioactivity between 30 min to 2 hr and remained high up to 6 hr. In the other tissues examined, maximum amount of radioactivity was seen at 15 min followed by a marked fall at 30 min and also at other subsequent intervals. The pattern of uptake and retention of radioactivity after administration of liposomal estradiol was not much different from that of free estradiol between 1 and 6 hr. A moderate increase in the amount of radioactivity in the nongenital tissues at 24 hr was the only difference noticed with liposomal estradiol. It is concluded that targeting of estradiol preferentially to the uterus could not be achieved through a liposomal delivery system.

  17. Liposomes to target peripheral neurons and Schwann cells.

    Directory of Open Access Journals (Sweden)

    Sooyeon Lee

    Full Text Available While a wealth of literature for tissue-specific liposomes is emerging, optimal formulations to target the cells of the peripheral nervous system (PNS are lacking. In this study, we asked whether a novel formulation of phospholipid-based liposomes could be optimized for preferential uptake by microvascular endothelia, peripheral neurons and Schwann cells. Here, we report a unique formulation consisting of a phospholipid, a polymer surfactant and cholesterol that result in enhanced uptake by targeted cells. Using fluorescently labeled liposomes, we followed particle internalization and trafficking through a distinct route from dextran and escape from degradative compartments, such as lysosomes. In cultures of non-myelinating Schwann cells, liposomes associate with the lipid raft marker Cholera toxin, and their internalization is inhibited by disruption of lipid rafts or actin polymerization. In contrast, pharmacological inhibition of clathrin-mediated endocytosis does not significantly impact liposome entry. To evaluate the efficacy of liposome targeting in tissues, we utilized myelinating explant cultures of dorsal root ganglia and isolated diaphragm preparations, both of which contain peripheral neurons and myelinating Schwann cells. In these models, we detected preferential liposome uptake into neurons and glial cells in comparison to surrounding muscle tissue. Furthermore, in vivo liposome administration by intramuscular or intravenous injection confirmed that the particles were delivered to myelinated peripheral nerves. Within the CNS, we detected the liposomes in choroid epithelium, but not in myelinated white matter regions or in brain parenchyma. The described nanoparticles represent a novel neurophilic delivery vehicle for targeting small therapeutic compounds, biological molecules, or imaging reagents into peripheral neurons and Schwann cells, and provide a major advancement toward developing effective therapies for peripheral

  18. Influence of the Encapsulation Efficiency and Size of Liposome on the Oral Bioavailability of Griseofulvin-Loaded Liposomes

    Directory of Open Access Journals (Sweden)

    Sandy Gim Ming Ong

    2016-08-01

    Full Text Available The objective of the present study was to investigate the influence of the encapsulation efficiency and size of liposome on the oral bioavailability of griseofulvin-loaded liposomes. Griseofulvin-loaded liposomes with desired characteristics were prepared from pro-liposome using various techniques. To study the effect of encapsulation efficiency, three preparations of griseofulvin, namely, griseofulvin aqueous suspension and two griseofulvin-loaded liposomes with different amounts of griseofulvin encapsulated [i.e., F1 (32% and F2(98%], were administered to rats. On the other hand, to study the effect of liposome size, the rats were given three different griseofulvin-loaded liposomes of various sizes, generated via different mechanical dispersion techniques [i.e., FTS (142 nm, MS (357 nm and NS (813 nm], but with essentially similar encapsulation efficiencies (about 93%. Results indicated that the extent of bioavailability of griseofulvin was improved 1.7–2.0 times when given in the form of liposomes (F1 compared to griseofulvin suspension. Besides that, there was an approximately two-fold enhancement of the extent of bioavailability following administration of griseofulvin-loaded liposomes with higher encapsulation efficiency (F2, compared to those of F1. Also, the results showed that the extent of bioavailability of liposomal formulations with smaller sizes were higher by approximately three times compared to liposomal formulation of a larger size. Nevertheless, a further size reduction of griseofulvin-loaded liposome (≤400 nm did not promote the uptake or bioavailability of griseofulvin. In conclusion, high drug encapsulation efficiency and small liposome size could enhance the oral bioavailability of griseofulvin-loaded liposomes and therefore these two parameters deserve careful consideration during formulation.

  19. PEGylated polylysine dendrimers increase lymphatic exposure to doxorubicin when compared to PEGylated liposomal and solution formulations of doxorubicin.

    Science.gov (United States)

    Ryan, Gemma M; Kaminskas, Lisa M; Bulitta, Jürgen B; McIntosh, Michelle P; Owen, David J; Porter, Christopher J H

    2013-11-28

    Improved delivery of chemotherapeutic drugs to the lymphatic system has the potential to augment outcomes for cancer therapy by enhancing activity against lymph node metastases. Uptake of small molecule chemotherapeutics into the lymphatic system, however, is limited. Nano-sized drug carriers have the potential to promote access to the lymphatics, but to this point, this has not been examined in detail. The current study therefore evaluated the lymphatic exposure of doxorubicin after subcutaneous and intravenous administration as a simple solution formulation or when formulated as a doxorubicin loaded PEGylated poly-lysine dendrimer (hydrodynamic diameter 12 nm), a PEGylated liposome (100 nm) and various pluronic micellar formulations (~5 nm) to thoracic lymph duct cannulated rats. Plasma and lymph pharmacokinetics were analysed by compartmental pharmacokinetic modelling in S-ADAPT, and Berkeley Madonna software was used to predict the lymphatic exposure of doxorubicin over an extended period of time. The micelle formulations displayed poor in vivo stability, resulting in doxorubicin profiles that were similar to that observed after administration of the doxorubicin solution formulation. In contrast, the dendrimer formulation significantly increased the recovery of doxorubicin in the thoracic lymph after both intravenous and subcutaneous dosing when compared to the solution or micellar formulation. Dendrimer-doxorubicin also resulted in increases in lymphatic doxorubicin concentrations when compared to the liposome formulation, although liposomal doxorubicin did increase lymphatic transport when compared to the solution formulation. Specifically, the dendrimer formulation increased the recovery of doxorubicin in the lymph up to 30 h post dose by up to 685 fold and 3.7 fold when compared to the solution and liposomal formulations respectively. Using the compartmental model to predict lymphatic exposure to longer time periods suggested that doxorubicin exposure to

  20. Manganese and Gd-DTPA stearyl liposomes as reticuloendothelial-system-specific MR imaging contrast agents

    International Nuclear Information System (INIS)

    Wuthrich, R.; Schwendener, R.; Duewell, S.; VonSchulthess, G.K.; Fuchs, W.A.

    1988-01-01

    Liposomes can be used to target metal ions as MR contrast agents to liver and spleen. It was the aim of this work to examine unilamellar liposomes containing manganese and gadolinium ions with respect to their targetting ability, contrast enhancement, and in vivo kinetics in rats and dogs. Unilamellar liposomes containing DTPA stearate were complexed with Mn/sup 2+/ and Gd/sup 3+/ resulting in vesicles of 30-40 nm. Injected into rats, approximately 35% of manganese liposomes were present in the liver after 30-60 minutes, and after 24 hours more than 80% had been eliminated. The pharmacokinetics of gadolinium were more protracted. In MR imaging, a reduction in the T1 of the liver parenchyma from 450 to 170 and 280 msec was observed for manganese and gadolinium liposomes (0.03 mmol/kg body weight), respectively, with the liver appearing as bright as fat. Manganese (and Gd-DTPA) stearyl liposomes are potential organ-selective contrast agents for liver and spleen and are eliminated through a hepatobiliary route

  1. Development of a novel cell-based assay system EPISSAY for screening epigenetic drugs and liposome formulated decitabine

    International Nuclear Information System (INIS)

    Lim, Sue Ping; Callen, David F; Kumar, Raman; Akkamsetty, Yamini; Wang, Wen; Ho, Kristen; Neilsen, Paul M; Walther, Diego J; Suetani, Rachel J; Prestidge, Clive

    2013-01-01

    Despite the potential of improving the delivery of epigenetic drugs, the subsequent assessment of changes in their epigenetic activity is largely dependent on the availability of a suitable and rapid screening bioassay. Here, we describe a cell-based assay system for screening gene reactivation. A cell-based assay system (EPISSAY) was designed based on a silenced triple-mutated bacterial nitroreductase TMnfsB fused with Red-Fluorescent Protein (RFP) expressed in the non-malignant human breast cell line MCF10A. EPISSAY was validated using the target gene TXNIP, which has previously been shown to respond to epigenetic drugs. The potency of a epigenetic drug model, decitabine, formulated with PEGylated liposomes was also validated using this assay system. Following treatment with DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors such as decitabine and vorinostat, increases in RFP expression were observed, indicating expression of RFP-TMnfsB. The EPISSAY system was then used to test the potency of decitabine, before and after PEGylated liposomal encapsulation. We observed a 50% higher potency of decitabine when encapsulated in PEGylated liposomes, which is likely to be due to its protection from rapid degradation. The EPISSAY bioassay system provides a novel and rapid system to compare the efficiencies of existing and newly formulated drugs that reactivate gene expression

  2. The cell-free integration of a polytopic mitochondrial membrane protein into liposomes occurs cotranslationally and in a lipid-dependent manner.

    Directory of Open Access Journals (Sweden)

    Ashley R Long

    Full Text Available The ADP/ATP Carrier (AAC is the most abundant transporter of the mitochondrial inner membrane. The central role that this transporter plays in cellular energy production highlights the importance of understanding its structure, function, and the basis of its pathologies. As a means of preparing proteoliposomes for the study of membrane proteins, several groups have explored the use of cell-free translation systems to facilitate membrane protein integration directly into preformed unilamellar vesicles without the use of surfactants. Using AAC as a model, we report for the first time the detergent-free reconstitution of a mitochondrial inner membrane protein into liposomes using a wheat germ-based in vitro translation system. Using a host of independent approaches, we demonstrate the efficient integration of AAC into vesicles with an inner membrane-mimetic lipid composition and, more importantly, that the integrated AAC is functionally active in transport. By adding liposomes at different stages of the translation reaction, we show that this direct integration is obligatorily cotranslational, and by synthesizing stable ribosome-bound nascent chain intermediates, we show that the nascent AAC polypeptide interacts with lipid vesicles while ribosome-bound. Finally, we show that the presence of the phospholipid cardiolipin in the liposomes specifically enhances AAC translation rate as well as the efficiency of vesicle association and integration. In light of these results, the possible mechanisms of liposome-assisted membrane protein integration during cell-free translation are discussed with respect to the mode of integration and the role of specific lipids.

  3. A spectroscopic study on stability of curcumin as a function of pH in silica nanoformulations, liposome and serum protein

    Science.gov (United States)

    Jain, Beena

    2017-02-01

    The effect of pH on the stability of curcumin formulated with different carriers has been studied spectroscopically. This was investigated by monitoring the absorption and emission kinetics and fluorescence decay time of four different curcumin formulations suspended in buffer with pH varying from 5 to 8.5. The carriers were organically modified silica NP (SiNP) having 3-amino propyl and/or vinyl groups, liposome and serum protein. The results reveal that stability of curcumin formulated with SiNP functionalized with 3-amino propyl group (SiNP-VA) is significantly higher as compared to SiNP with only vinyl group (SiNP-V) and buffer but lower as compared to serum protein and liposome. However, fluorescence quantum yield (QY) is highest in SiNP-VA among all the nano formulations at pH 7.4 and below, which is attributed to the excited state interaction of curcumin with the amino groups of SiNP-VA. Results suggest that SiNP-VA could be an effective carrier for curcumin, which may have applications for imaging and drug delivery.

  4. Preparation, characterization, and efficient transfection of cationic liposomes and nanomagnetic cationic liposomes

    Directory of Open Access Journals (Sweden)

    Samadikhah HR

    2011-10-01

    Full Text Available Hamid Reza Samadikhah1,*, Asia Majidi2,*, Maryam Nikkhah2, Saman Hosseinkhani11Department of Biochemistry, 2Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran *These authors contributed equally to this work Purpose: Cationic liposomes (CLs are composed of phospholipid bilayers. One of the most important applications of these particles is in drug and gene delivery. However, using CLs to deliver therapeutic nucleic acids and drugs to target organs has some problems, including low transfection efficiency in vivo. The aim of this study was to develop novel CLs containing magnetite to overcome the deficiencies. Patients and methods: CLs and magnetic cationic liposomes (MCLs were prepared using the freeze-dried empty liposome method. Luciferase-harboring vectors (pGL3 were transferred into liposomes and the transfection efficiencies were determined by luciferase assay. Firefly luciferase is one of most popular reporter genes often used to measure the efficiency of gene transfer in vivo and in vitro. Different formulations of liposomes have been used for delivery of different kinds of gene reporters. Lipoplex (liposome–plasmid DNA complexes formation was monitored by gel retardation assay. Size and charge of lipoplexes were determined using particle size analysis. Chinese hamster ovary cells were transfected by lipoplexes (liposome-pGL3; transfection efficiency and gene expression level was evaluated by luciferase assay. Results: High transfection efficiency of plasmid by CLs and novel nanomagnetic CLs was achieved. Moreover, lipoplexes showed less cytotoxicity than polyethyleneimine and Lipofectamine™. Conclusion: Novel liposome compositions (1,2-dipalmitoyl-sn-glycero-3-phosphocholine [DPPC]/dioctadecyldimethylammonium bromide [DOAB] and DPPC/cholesterol/DOAB with high transfection efficiency can be useful in gene delivery in vitro. MCLs can also be used for targeted gene delivery, due to

  5. Tissue distribution of radiolabeled phosphatidylserine-containing liposome in mice

    International Nuclear Information System (INIS)

    Borborema, Samanta E.T.; Nascimento, Nanci do; Osso Junior, Joao A.

    2009-01-01

    Liposomes are used as drug delivery systems to modify pharmacokinetic of drugs and also to improve their action in target cells. Liposomes containing phosphatidylserine are efficiently eliminated from the blood by cells of the mononuclear phagocytic system (MPS), predominantly Kupffer cells in the liver. In this way, this is a valuable approach to treat infectious diseases involving MPS, especially leishmaniasis. Leishmaniasis is a severe parasitic disease, caused by intramacrophage protozoa Leishmania sp., and is fatal if left untreated. Leishmania resides mainly in the liver and the spleen. Antileishmanial agents containing-liposomes showed more effective therapies with reduction of toxicity and adverse side effects. The purpose of this study was to investigate the tissue distribution of radioactive meglumine antimoniate encapsulated in phosphatidylserine-containing liposome. Meglumine antimoniate was neutron irradiated inside the IEA-R1 nuclear reactor to produce antimony radiotracers, 122 Sb and 124 Sb, and encapsulated in liposome. Healthy mice received a single intraperitoneal dose of the radiolabeled drug. Analysis of the mean radioactive tissue concentration-time data curves showed that liver and spleen had the highest levels of radioactivity. In addition these levels of drug remained for more than 48 hours. The dominant route of elimination was via biliary excretion with slow rate. Small fraction of the drug was found in the kidneys with very fast elimination. In conclusion, the phosphatidylserine-containing liposome showed to be a very useful tool to target antileishmanial agents to MPS and to sustain the drug levels for longer times. Besides, radiolabeled liposome is the easiest approach to perform biodistribution evaluation. (author)

  6. Tissue distribution of radiolabeled phosphatidylserine-containing liposome in mice

    Energy Technology Data Exchange (ETDEWEB)

    Borborema, Samanta E.T.; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Biotecnologia], e-mail: samanta@usp.br, e-mail: nnascime@ipen.br; Andrade Junior, Heitor F. de [Instituto de Medicina Tropical de Sao Paulo (IMTSP), Sao Paulo, SP (Brazil)], e-mail: hfandrad@usp.br; Osso Junior, Joao A. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Radiofarmacia], e-mail: jaosso@ipen.br

    2009-07-01

    Liposomes are used as drug delivery systems to modify pharmacokinetic of drugs and also to improve their action in target cells. Liposomes containing phosphatidylserine are efficiently eliminated from the blood by cells of the mononuclear phagocytic system (MPS), predominantly Kupffer cells in the liver. In this way, this is a valuable approach to treat infectious diseases involving MPS, especially leishmaniasis. Leishmaniasis is a severe parasitic disease, caused by intramacrophage protozoa Leishmania sp., and is fatal if left untreated. Leishmania resides mainly in the liver and the spleen. Antileishmanial agents containing-liposomes showed more effective therapies with reduction of toxicity and adverse side effects. The purpose of this study was to investigate the tissue distribution of radioactive meglumine antimoniate encapsulated in phosphatidylserine-containing liposome. Meglumine antimoniate was neutron irradiated inside the IEA-R1 nuclear reactor to produce antimony radiotracers, {sup 122}Sb and {sup 124}Sb, and encapsulated in liposome. Healthy mice received a single intraperitoneal dose of the radiolabeled drug. Analysis of the mean radioactive tissue concentration-time data curves showed that liver and spleen had the highest levels of radioactivity. In addition these levels of drug remained for more than 48 hours. The dominant route of elimination was via biliary excretion with slow rate. Small fraction of the drug was found in the kidneys with very fast elimination. In conclusion, the phosphatidylserine-containing liposome showed to be a very useful tool to target antileishmanial agents to MPS and to sustain the drug levels for longer times. Besides, radiolabeled liposome is the easiest approach to perform biodistribution evaluation. (author)

  7. Recent advancements in liposomes targeting strategies to cross blood-brain barrier (BBB) for the treatment of Alzheimer's disease.

    Science.gov (United States)

    Agrawal, Mukta; Ajazuddin; Tripathi, Dulal K; Saraf, Swarnlata; Saraf, Shailendra; Antimisiaris, Sophia G; Mourtas, Spyridon; Hammarlund-Udenaes, Margareta; Alexander, Amit

    2017-08-28

    In this modern era, with the help of various advanced technologies, medical science has overcome most of the health-related issues successfully. Though, some diseases still remain unresolved due to various physiological barriers. One such condition is Alzheimer; a neurodegenerative disorder characterized by progressive memory impairment, behavioral abnormalities, mood swing and disturbed routine activities of the person suffering from. It is well known to all that the brain is entirely covered by a protective layer commonly known as blood brain barrier (BBB) which is responsible to maintain the homeostasis of brain by restricting the entry of toxic substances, drug molecules, various proteins and peptides, small hydrophilic molecules, large lipophilic substances and so many other peripheral components to protect the brain from any harmful stimuli. This functionally essential structure creates a major hurdle for delivery of any drug into the brain. Still, there are some provisions on BBB which facilitate the entry of useful substances in the brain via specific mechanisms like passive diffusion, receptor-mediated transcytosis, carrier-mediated transcytosis etc. Another important factor for drug transport is the selection of a suitable drug delivery systems like, liposome, which is a novel drug carrier system offering a potential approach to resolving this problem. Its unique phospholipid bilayer structure (similar to physiological membrane) had made it more compatible with the lipoidal layer of BBB and helps the drug to enter the brain. The present review work focused on various surface modifications with functional ligand (like lactoferrin, transferrin etc.) and carrier molecules (such as glutathione, glucose etc.) on the liposomal structure to enhance its brain targeting ability towards the successful treatment of Alzheimer disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Transforming lipid-based oral drug delivery systems into solid dosage forms: an overview of solid carriers, physicochemical properties, and biopharmaceutical performance.

    Science.gov (United States)

    Tan, Angel; Rao, Shasha; Prestidge, Clive A

    2013-12-01

    The diversity of lipid excipients available commercially has enabled versatile formulation design of lipid-based drug delivery systems for enhancing the oral absorption of poorly water-soluble drugs, such as emulsions, microemulsions, micelles, liposomes, niosomes and various self-emulsifying systems. The transformation of liquid lipid-based systems into solid dosage forms has been investigated for several decades, and has recently become a core subject of pharmaceutical research as solidification is regarded as viable means for stabilising lipid colloidal systems while eliminating stringent processing requirements associated with liquid systems. This review describes the types of pharmaceutical grade excipients (silica nanoparticle/microparticle, polysaccharide, polymer and protein-based materials) used as solid carriers and the current state of knowledge on the liquid-to-solid conversion approaches. Details are primarily focused on the solid-state physicochemical properties and redispersion capacity of various dry lipid-based formulations, and how these relate to the in vitro drug release and solubilisation, lipid carrier digestion and cell permeation performances. Numerous in vivo proof-of-concept studies are presented to highlight the viability of these dry lipid-based formulations. This review is significant in directing future research work in fostering translation of dry lipid-based formulations into clinical applications.

  9. Curcumin liposomes prepared with milk fat globule membrane phospholipids and soybean lecithin.

    Science.gov (United States)

    Jin, Hong-Hao; Lu, Qun; Jiang, Jian-Guo

    2016-03-01

    Using thin film ultrasonic dispersion method, the curcumin liposomes were prepared with milk fat globule membrane (MFGM) phospholipids and soybean lecithins, respectively, to compare the characteristics and stability of the 2 curcumin liposomes. The processing parameters of curcumin liposomes were investigated to evaluate their effects on the encapsulation efficiency. Curcumin liposomes were characterized in terms of size distribution, ζ-potential, and in vitro release behavior, and then their storage stability under various conditions was evaluated. The curcumin liposomes prepared with MFGM phospholipids had an encapsulation efficiency of about 74%, an average particle size of 212.3 nm, and a ζ-potential of -48.60 mV. The MFGM liposomes showed higher encapsulation efficiency, smaller particle size, higher absolute value of ζ-potential, and slower in vitro release than soybean liposomes. The retention rate of liposomal curcumin was significantly higher than that of free curcumin. The stability of the 2 liposomes under different pH was almost the same, but MFGM liposomes displayed a slightly higher stability than soybean liposomes under the conditions of Fe(3+), light, temperature, oxygen, and relative humidity. In conclusion, MFGM phospholipids have potential advantages in the manufacture of curcumin liposomes used in food systems. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  10. pH and temperature dual-sensitive liposome gel based on novel cleavable mPEG-Hz-CHEMS polymeric vaginal delivery system

    Directory of Open Access Journals (Sweden)

    Chen D

    2012-05-01

    Full Text Available Daquan Chen,1,2 Kaoxiang Sun,1,2 Hongjie Mu,1 Mingtan Tang,3 Rongcai Liang,1,2 Aiping Wang,1,2 Shasha Zhou,1 Haijun Sun,1 Feng Zhao,1 Jianwen Yao,1 Wanhui Liu1,21School of Pharmacy, Yantai University, 2State Key Laboratory of Longacting and Targeting Drug Delivery Systems, Yantai, 3School of Pharmaceutical Sciences, Shandong University, Jinan, People's Republic of ChinaBackground: In this study, a pH and temperature dual-sensitive liposome gel based on a novel cleavable hydrazone-based pH-sensitive methoxy polyethylene glycol 2000-hydrazone-cholesteryl hemisuccinate (mPEG-Hz-CHEMS polymer was used for vaginal administration.Methods: The pH-sensitive, cleavable mPEG-Hz-CHEMS was designed as a modified pH-sensitive liposome that would selectively degrade under locally acidic vaginal conditions. The novel pH-sensitive liposome was engineered to form a thermogel at body temperature and to degrade in an acidic environment.Results: A dual-sensitive liposome gel with a high encapsulation efficiency of arctigenin was formed and improved the solubility of arctigenin characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. The dual-sensitive liposome gel with a sol-gel transition at body temperature was degraded in a pH-dependent manner, and was stable for a long period of time at neutral and basic pH, but cleavable under acidic conditions (pH 5.0. Arctigenin encapsulated in a dual-sensitive liposome gel was more stable and less toxic than arctigenin loaded into pH-sensitive liposomes. In vitro drug release results indicated that dual-sensitive liposome gels showed constant release of arctigenin over 3 days, but showed sustained release of arctigenin in buffers at pH 7.4 and pH 9.0.Conclusion: This research has shed some light on a pH and temperature dual-sensitive liposome gel using a cleavable mPEG-Hz-CHEMS polymer for vaginal delivery.Keywords: mPEG-Hz-CHEMS polymer, pH-sensitive liposomes, thermosensitive

  11. Targeted drug delivery using temperature-sensitive liposomes

    International Nuclear Information System (INIS)

    Magin, R.L.; Niesman, M.R.

    1984-01-01

    Liposomes are receiving considerable attention as vehicles for selective drug delivery. One method of targeting liposomal contents involves the combination of local hyperthermia with temperature-sensitive liposomes. Such liposomes have been used to increase the uptake of methotrexate and cis-platinum into locally heated mouse tumors. However, additional information is needed on the mechanism of liposome drug release and the physiologic deposition of liposomes in vivo before clinical trails are begun. Current research is directed at studying the encapsulation and release of water soluble drugs from temperature-sensitive liposomes. The influence of liposome size, structure, and composition on the rapid release in plasma of cytosine arabinoside, cis-platinum, and the radiation sensitizer SR-2508 are described. These results demonstrate potential applications for temperature-sensitive liposomes in selective drug delivery

  12. The influence of oscillating electromagnetic fields on membrane structure and function: Synthetic liposome and natural membrane bilayer systems with direct application to the controlled delivery of chemical agents

    International Nuclear Information System (INIS)

    Liburdy, R.P.; de Manincor, D.; Fingado, B.

    1989-09-01

    Investigations have been conducted to determine if an imposed electromagnetic field can influence membrane transport, and ion and drug permeability in both synthetic and natural cell membrane systems. Microwave fields enhance accumulation of sodium in the lymphocyte and induce protein shedding at Tc. Microwaves also trigger membrane permeability of liposome systems under specific field exposure conditions. Sensitivity varies in a defined way in bilayers displaying a membrane structural phase transition temperature, Tc; maximal release was observed at or near Tc. Significantly, liposome systems without a membrane phase transition were also found to experience permeability increases but, in contrast, this response was temperature independent. The above results indicate that field-enhanced drug release occurs in liposome vesicles that possess a Tc as well as non-Tc liposomes. Additional studies extend non-Tc liposome responses to the in vivo case in which microwaves trigger Gentamicin release from a liposome ''depot'' placed subcutaneously in the rat hind leg. In addition, evidence is provided that cell surface sequestered liposomes can be triggered by microwave fields to release drugs directly into target cells. 24 refs., 6 figs

  13. The role of surfactants in the formulation of elastic liposomal gels containing a synthetic opioid analgesic

    Directory of Open Access Journals (Sweden)

    Singh S

    2016-04-01

    Full Text Available Sima Singh,1,* Harsh Vardhan,1,* Niranjan G Kotla,2 Balaji Maddiboyina,3 Dinesh Sharma,4 Thomas J Webster5,6 1School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India; 2Center for Research in Medical Devices, National University of Ireland, Galway, Ireland; 3Department of Pharmaceutics, Vishwabharathi College of Pharmaceutical Sciences, Guntur, India; 4Ranbaxy Laboratory Ltd, Gurgaon, India; 5Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 6Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia *These authors contributed equally to this work Abstract: Transdermal drug delivery systems have made significant contributions to the medical community, but have yet to completely substitute oral or parenteral delivery. Recently, various strategies have been used to augment the transdermal delivery of therapeutics. Primarily, they include iontophoresis, electrophoresis, sonophoresis, chemical permeation enhancers, microneedles, and vesicular systems. Among these strategies, elastic liposomes appear promising. Elastic vesicle scaffolds have been developed and evaluated as novel topical and transdermal delivery systems, with an infrastructure consisting of hydrophobic and hydrophilic moieties together, and as a result, such scaffolds can accommodate drug molecules with a wide range of solubility. High deformability of these vesicles provides for better penetration of intact vesicles. This system is much more efficient at delivering low- and high-molecular-weight drugs to the skin in terms of quantity and depth. In this work, elastic liposomes of Tramadol HCl were prepared using a solvent evaporation method with different surfactants and were characterized using microscopy, and particle size, shape, drug content, ex vivo release, and zeta potential were also calculated. The prepared elastic liposomes were found to be in the range of 152.4 nm with a zeta

  14. Uji Aktivitas Antiproliferasi Formula Liposom Ekstrak Etanol Kunyit (Curcuma domestica Terhadap Sel Kanker Payudara T47D

    Directory of Open Access Journals (Sweden)

    Gabriella Pasaribu

    2016-04-01

    Full Text Available Breast cancer is one of deadliest diseases in the world. Turmeric extract was known to have antiproliferative activity. To minimize its toxicity, turmeric extract was encapsulated with liposome, a vesicle lipid bilayer that was functioned as cancer drug carrier in body. This research aimed to determine encapsulation effect of turmeric extract against antiproliferative activity in T47D breast cancer cells through in vitro assay. Liposomes was made using thin layer method and particle size was reduced by extrusion. Materials that was used phosphatidylcholine, cholesterol, and turmeric extract. Optimization of liposomes was made in three formulations with different extract concentrations. The most optimal formulation was formulation with less extract and physical parameters which have smallest precipitates and longest settling time. Evaluation liposome particle size and zeta potential were used DLS, morphology was used TEM, and entrapment efficiency was used dialysis. The most optimal formulation was tested their antiproliferative activity compared with not encapsulated extracts used 3-(4,5-dimethylazole-2-yl-2,5-diphenyltetrazolium bromide (MTT method. The result showed that there was antiproliferative activity in encapsulated extracts. IC50 encapsulated extracts was 45.762 μg/ml and IC50 extracts was 36.399 μg/ml. Liposome particle size was below 445 nm. Zeta potential was -7.51 mV. Morphology was LUV and MVV. Entrapment efficiency was 63.80%. It could be concluded that encapsulation of turmeric extract into liposome could reduce its toxicity against cancer cells.

  15. Liposomal Encapsulation for Systemic Delivery of Propranolol via Transdermal Iontophoresis Improves Bone Microarchitecture in Ovariectomized Rats.

    Science.gov (United States)

    Teong, Benjamin; Kuo, Shyh Ming; Tsai, Wei-Hsin; Ho, Mei-Ling; Chen, Chung-Hwan; Huang, Han Hsiang

    2017-04-13

    The stimulatory effects of liposomal propranolol (PRP) on proliferation and differentiation of human osteoblastic cells suggested that the prepared liposomes-encapsulated PRP exerts anabolic effects on bone in vivo. Iontophoresis provides merits such as sustained release of drugs and circumvention of first pass metabolism. This study further investigated and evaluated the anti-osteoporotic effects of liposomal PRP in ovariectomized (OVX) rats via iontophoresis. Rats subjected to OVX were administered with pure or liposomal PRP via iontophoresis or subcutaneous injection twice a week for 12 weeks. Changes in the microarchitecture at the proximal tibia and the fourth lumbar spine were assessed between pure or liposomal PRP treated and non-treated groups using micro-computed tomography. Administration of liposomal PRP at low dose (0.05 mg/kg) via iontophoresis over 2-fold elevated ratio between bone volume and total tissue volume (BV/TV) in proximal tibia to 9.0% whereas treatment with liposomal PRP at low and high (0.5 mg/kg) doses via subcutaneous injection resulted in smaller increases in BV/TV. Significant improvement of BV/TV and bone mineral density (BMD) was also found in the fourth lumbar spine when low-dose liposomal PRP was iontophoretically administered. Iontophoretic low-dose liposomal PRP also elevated trabecular numbers in tibia and trabecular thickness in spine. Enhancement of bone microarchitecture volumes has highlighted that liposomal formulation with transdermal iontophoresis is promising for PRP treatment at the lower dose and with longer duration than its clinical therapeutic range and duration to exhibit optimal effects against bone loss in vivo.

  16. Propulsion of liposomes using bacterial motors

    International Nuclear Information System (INIS)

    Zhang Zhenhai; Li Kejie; Li Zhifei; Yu Wei; Xie Zhihong; Shi Zhiguo

    2013-01-01

    Here we describe the utilization of flagellated bacteria as actuators to propel spherical liposomes by attaching bacteria to the liposome surface. Bacteria were stably attached to liposomes using a cross-linking antibody. The effect of the number of attached bacteria on propulsion speed was experimentally determined. The effects of bacterial propulsion on the bacteria–antibody–liposome complex were stochastic. We demonstrated that liposomal mobility increased when bacteria were attached, and the propulsion speed correlated with the number of bacteria. (paper)

  17. Prospects of liposomes using for creating of new forms of the medicinal and preventive preparations

    Directory of Open Access Journals (Sweden)

    M. A. Kisjakova

    2010-07-01

    Full Text Available Information on the structure, physical and chemical characteristics of the phospholipid vesicles (liposomes – the effective natural drug delivery system is presented. Types of liposomes, procedures of its productions, penetration mechanisms into cells and functional features of liposomal drugs are described. Data on production of liposomes with lactobacilli acellular homogenates and the methods of the liposomes structure control asre demonstrated.

  18. Structure of liposome encapsulating proteins characterized by X-ray scattering and shell-modeling

    International Nuclear Information System (INIS)

    Hirai, Mitsuhiro; Kimura, Ryota; Takeuchi, Kazuki; Hagiwara, Yoshihiko; Kawai-Hirai, Rika; Ohta, Noboru; Igarashi, Noriyuki; Shimuzu, Nobutaka

    2013-01-01

    Wide-angle X-ray scattering data using a third-generation synchrotron radiation source are presented. Lipid liposomes are promising drug delivery systems because they have superior curative effects owing to their high adaptability to a living body. Lipid liposomes encapsulating proteins were constructed and the structures examined using synchrotron radiation small- and wide-angle X-ray scattering (SR-SWAXS). The liposomes were prepared by a sequential combination of natural swelling, ultrasonic dispersion, freeze-throw, extrusion and spin-filtration. The liposomes were composed of acidic glycosphingolipid (ganglioside), cholesterol and phospholipids. By using shell-modeling methods, the asymmetric bilayer structure of the liposome and the encapsulation efficiency of proteins were determined. As well as other analytical techniques, SR-SWAXS and shell-modeling methods are shown to be a powerful tool for characterizing in situ structures of lipid liposomes as an important candidate of drug delivery systems

  19. Preparation and characterization of clove essential oil-loaded liposomes.

    Science.gov (United States)

    Sebaaly, Carine; Jraij, Alia; Fessi, Hatem; Charcosset, Catherine; Greige-Gerges, Hélène

    2015-07-01

    In this study, suitable formulations of natural soybean phospholipid vesicles were developed to improve the stability of clove essential oil and its main component, eugenol. Using an ethanol injection method, saturated (Phospholipon 80H, Phospholipon 90H) and unsaturated soybean (Lipoid S100) phospholipids, in combination with cholesterol, were used to prepare liposomes at various eugenol and clove essential oil concentrations. Liposomal batches were characterized and compared for their size, polydispersity index, Zeta potential, loading rate, encapsulation efficiency and morphology. The liposomes were tested for their stability after storing them for 2 months at 4°C by monitoring changes in their mean size, polydispersity index and encapsulation efficiency (EE) values. It was found that liposomes exhibited nanometric oligolamellar and spherical shaped vesicles and protected eugenol from degradation induced by UV exposure; they also maintained the DPPH-scavenging activity of free eugenol. Liposomes constitute a suitable system for encapsulation of volatile unstable essential oil constituents. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Detection of peritoneal dissemination with near-infrared fluorescence laparoscopic imaging using a liposomal formulation of a synthesized indocyanine green liposomal derivative.

    Science.gov (United States)

    Hoshino, Isamu; Maruyama, Tetsuro; Fujito, Hiromichi; Tamura, Yutaka; Suganami, Akiko; Hayashi, Hideki; Toyota, Taro; Akutsu, Yasunori; Murakami, Kentaro; Isozaki, Yuka; Akanuma, Naoki; Takeshita, Nobuyoshi; Toyozumi, Takeshi; Komatsu, Aki; Matsubara, Hisahiro

    2015-03-01

    Although conventional staging laparoscopy (SL) has improved the diagnostic accuracy of peritoneal dissemination, novel technology is needed to increase the sensitivity of SL. We herein describe a new imaging method employing near-infrared (NIR) fluorescence imaging using a liposomal synthesized indocyanine green (ICG) liposomal derivative, LP-ICG-C18. LP-ICG-C18 is a NIR-photoactivating probe in which an ICG fluorophore is covalently conjugated with a phospholipid moiety. Nude mice were intraperitoneally injected with gastric cancer cells. Twelve days later, the mice were given intravenous injections of LP-ICG-C18 at a dose of 0.15 mg/kg. A NIR imaging system was used to identify the disseminated tumors. The disseminated nodules in mice were detected without any difficulties. Disseminated tumor nodules were collected from mice with or without injections of liposomal formulation and were transferred into the swine peritoneal cavity. The nodules in the swine peritoneal cavity were clearly and promptly defined by the NIR imaging system. NIR-fluorescing liposomal probes can effectively target peritoneal disseminated tumors and can be easily detected by a NIR imaging system. These results warrant future clinical trials of our imaging system and may contribute to a more precise diagnosis and therapeutic approach for gastric cancer patients. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. Hyaluronan-conjugated liposomes encapsulating gemcitabine for breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    Han NK

    2016-04-01

    Full Text Available Na-Kyung Han,1,* Dae Hwan Shin,1,* Jung Seok Kim,1 Kwon Yeon Weon,2 Chang-Young Jang,1 Jin-Seok Kim1 1Research Center for Cell Fate Control (RCCFC and College of Pharmacy, Sookmyung Women’s University, Seoul, 2College of Pharmacy, Catholic University of Daegu, Gyeongbuk, Korea *These authors contributed equally to this work Abstract: Investigation of potential therapeutics for targeting breast cancer stem cells (BCSCs is important because these cells are regarded as culprit of breast cancer relapse. Accomplishing this kind of strategy requires a specific drug-delivery system using the distinct features of liposomes. Studies on targeted liposomal delivery systems have indicated the conjugation of hyaluronan (HA, a primary ligand for CD44 surface markers, as an appropriate method for targeting BCSCs. For this study, enriched BCSCs were obtained by culturing MCF-7 breast cancer cells in nonadherent conditions. The enriched BCSCs were challenged with HA-conjugated liposomes encapsulating gemcitabine (2, 2-difluoro-2-deoxycytidine, GEM. In vitro study showed that the HA-conjugated liposomes significantly enhanced the cytotoxicity, anti-migration, and anti-colony formation abilities of GEM through targeting of CD44 expressed on BCSCs. In pharmacokinetic study, area under the drug concentration vs time curve (AUC of the immunoliposomal GEM was 3.5 times higher than that of free GEM, indicating that the HA-conjugated liposomes enhanced the stability of GEM in the bloodstream and therefore prolonged its half-life time. The antitumor effect of the immunoliposomal GEM was 3.3 times higher than that of free GEM in a xenograft mouse model, probably reflecting the unique targeting of the CD44 receptor by HA and the increased cytotoxicity and stability through the liposomal formulation. Furthermore, marginal change in body weight demonstrated that the use of liposomes considerably reduced the systemic toxicity of GEM on normal healthy cells. Taken together

  2. Cross-linkable liposomes stabilize a magnetic resonance contrast-enhancing polymeric fastener.

    Science.gov (United States)

    Smith, Cartney E; Kong, Hyunjoon

    2014-04-08

    Liposomes are commonly used to deliver drugs and contrast agents to their target site in a controlled manner. One of the greatest obstacles in the performance of such delivery vehicles is their stability in the presence of serum. Here, we demonstrate a method to stabilize a class of liposomes that load gadolinium, a magnetic resonance (MR) contrast agent, as a model cargo on their surfaces. We hypothesized that the sequential adsorption of a gadolinium-binding chitosan fastener on the liposome surface followed by covalent cross-linking of the lipid bilayer would provide enhanced stability and improved MR signal in the presence of human serum. To investigate this hypothesis, liposomes composed of diyne-containing lipids were assembled and functionalized via chitosan conjugated with a hydrophobic anchor and diethylenetriaminepentaacetic acid (DTPA). This postadsorption cross-linking strategy served to stabilize the thermodynamically favorable association between liposome and polymeric fastener. Furthermore, the chitosan-coated, cross-linked liposomes proved more effective as delivery vehicles of gadolinium than uncross-linked liposomes due to the reduced liposome degradation and chitosan desorption. Overall, this study demonstrates a useful method to stabilize a broad class of particles used for systemic delivery of various molecular payloads.

  3. Nanoparticle Stabilized Liposomes for Acne Therapy

    Science.gov (United States)

    Fu, Victoria

    Acne vulgaris is a common skin disease that affects over 40 million people in the United States alone. The main cause of acne vulgaris is Propionibacterium acnes (P. acnes), resides deep in the pores and follicles of the skin in order to feed on oil produced by the sebaceous glands. The liposome is a lipid based nanoparticle with numerous advantages over free drug molecules as an acne treatment alternative. Bare liposomes loaded with lauric acid (LipoLA) were found to show strong antimicrobial activity against P. acnes while generating minimal toxicity. However, the platform is limited by the spontaneous tendency of liposomes to fuse with each other. Attaching nanoparticles to the surface of liposomes can overcome this challenge by providing steric repulsion and reduce surface tension. Thus, carboxyl-functionalized gold nanoparticles (AuC) were attached to the surface of liposomes (AuC-liposomes) loaded with doxycycline, a general tetracycline antibiotic. These particles were found to have a diameter of 120 nm and a zeta potential of 20.0 mV. Both fluorescent and antimicrobial studies demonstrated that based on electrostatic interaction, negatively charged AuC attached to the liposome's positively charged surface and stabilized liposomes in a neutral pH environment (pH = 7.4). Upon entering the skin's acidic environment (pH = 4), AuC detached from the liposome's surface and liposomes could fuse with P. acnes residing in the pores. Furthermore, toxicity studies showed that AuC-liposomes did not induce any significant toxicity, while two of the leading over-the-counter therapies, benzoyl peroxide and salicylic acid, generated substantial skin irritation.

  4. Biological activity of liposomal vanillin.

    Science.gov (United States)

    Castan, Leniher; Del Toro, Grisel; Fernández, Adolfo A; González, Manuel; Ortíz, Emilia; Lobo, Daliana

    2013-06-01

    This article presents a study of vanillin encapsulation inside multilamellar liposomes, with emphasis on the evaluation of antioxidant activity, the hemolytic effect, and the antisickling properties of these products. Egg phosphatidylcholine-cholesterol and egg phosphatidylcholine-cholesterol-1-O-decylglycerol liposomes were prepared by mechanical dispersion, all with vanillin included. Vesicles were characterized by determination of encapsulation efficiency and vanillin retention capacity. Antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. The hemolytic effect of liposomes was also evaluated by spectrophotometry, as well as the antisickling activity by the Huck test using optical microscopy. Results showed that the lipid composition of liposomes did not significantly affect the encapsulation efficiency. Stable vesicles were obtained with a high retention percentage of vanillin. Liposomes exhibited a high capture of the DPPH radical compared to free vanillin and 1-O-decylglycerol (C10) in solution. Vesicles caused no significant hemolisys in normal erythrocytes, nor in those coming from patients with sickle cell anemia. Vanillin encapsulated in liposomes retained its antisickling activity, with a greater effect for C10-containing vesicles. Our results show that vanillin encapsulation in liposomes is a way to enhance the pharmacologic properties of this molecule using a suitable vehicle.

  5. Liposome based radiosensitizer cancer therapy

    DEFF Research Database (Denmark)

    Pourhassan, Houman

    Liposome-encapsulated chemotherapeutics have been used in the treatment of a variety of cancers and are feasible for use as mono-therapeutics as well as for combination therapy in conjunction with other modalities. Despite widespread use of liposomal drugs in cancer patient care, insufficient drug...... biomolecules. By modulating the liposomal membrane, liposomes can become sensitive towards enzymatically-driven destabilization and/or functionalization, thereby allowing control of the release of encapsulated therapeutics within the diseased tissue upon intrinsic stimulation from tumor-associated enzymes...... in tumor-bearing mice.The safety and efficacy of sPLA2-sensitive liposomal L-OHP was assessed in sPLA2-deficient FaDu hypopharyngeal squamous cell carcinoma and sPLA2-expressing Colo205 colorectal adenocarcinoma. Also, the feasibility of multimodal cancer therapy employing L-OHP encapsulated in MMP...

  6. Liposome kinetics in infarcted canine myocardium

    International Nuclear Information System (INIS)

    Caride, V.J.; Twickler, J.; Zaret, B.L.

    1984-01-01

    To study the mechanisms and kinetics of liposome deposition in the region of the experimental myocardial infarction, the myocardial distribution of positive and negative liposomes was determined as a function of regional myocardial blood flow and time after administration. The study was performed in dogs at 1 and 24 h following experimental myocardial infarction. Twenty-four hours after coronary artery occlusion, the initial myocardial distribution of positive and negative liposomes (2 min) is directly proportional to regional myocardial blood flow. With time, there is reduction of the radiotracer associated with negative liposomes from all myocardial regions (p less than 0.01). In contrast, in areas of moderate and severe blood flow reduction, there is progressive accumulation of tracers entrapped or incorporated in positive liposomes. This increment becomes significant in 120 min (p less than 0.005). Similar findings are observed in studies performed 1 h after coronary artery occlusion. Dual-label liposomes [( 3 H]cholesterol and [99mTc]diethylenetriamine pentaacetic acid) were used to study the integrity of liposomes in normal and ischemic myocardium. Significant dissociation of the aqueous and lipid labels of positive liposomes is observed 1 h following coronary artery occlusion. In the 24-h myocardial infarction model, dissociation of the aqueous and lipid labels in ischemic myocardium is also observed. This phenomenon is more pronounced with positive than with negative liposomes (p less than 0.02)

  7. PEG minocycline-liposomes ameliorate CNS autoimmune disease.

    Directory of Open Access Journals (Sweden)

    Wei Hu

    Full Text Available Minocycline is an oral tetracycline derivative with good bioavailability in the central nervous system (CNS. Minocycline, a potent inhibitor of matrix metalloproteinase (MMP-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. Potential adverse effects associated with long-term daily minocycline therapy in human patients are concerning. Here, we investigated whether less frequent treatment with long-circulating polyethylene glycol (PEG minocycline liposomes are effective in treating EAE.Performing in vitro time kinetic studies of PEG minocycline-liposomes in human peripheral blood mononuclear cells (PBMCs, we determined that PEG minocycline-liposome preparations stabilized with CaCl(2 are effective in diminishing MMP-9 activity. Intravenous injections of PEG minocycline-liposomes every five days were as effective in ameliorating clinical EAE as daily intraperitoneal injections of minocycline. Treatment of animals with PEG minocycline-liposomes significantly reduced the number of CNS-infiltrating leukocytes, and the overall expression of MMP-9 in the CNS. There was also a significant suppression of MMP-9 expression and proteolytic activity in splenocytes of treated animals, but not in CNS-infiltrating leukocytes. Thus, leukocytes gaining access to the brain and spinal cord require the same absolute amount of MMP-9 in all treatment groups, but minocycline decreases the absolute cell number.Our data indicate that less frequent injections of PEG minocycline-liposomes are an effective alternative pharmacotherapy to daily minocycline injections for the treatment of CNS autoimmune diseases. Also, inhibition of MMP-9 remains a promising treatment target in EAE and patients with MS.

  8. Formulation, Development, and In Vitro Evaluation of a CD22 Targeted Liposomal System Containing a Non-Cardiotoxic Anthracycline for B Cell Malignancies

    Directory of Open Access Journals (Sweden)

    Nivesh K. Mittal

    2018-04-01

    Full Text Available Doxorubicin cardiotoxicity has led to the development of superior chemotherapeutic agents such as AD 198. However, depletion of healthy neutrophils and thrombocytes from AD 198 therapy must be limited. This can be done by the development of a targeted drug delivery system that delivers AD 198 to the malignant cells. The current research highlights the development and in vitro analysis of targeted liposomes containing AD 198. The best lipids were identified and optimized for physicochemical effects on the liposomal system. Physiochemical characteristics such as size, ζ-potential, and dissolution were also studied. Active targeting to CD22 positive cells was achieved by conjugating anti-CD22 Fab’ to the liposomal surface. Size and ζ-potential of the liposomes was between 115 and 145 nm, and −8 to−15 mV. 30% drug was released over 72 h. Higher cytotoxicity was observed in CD22+ve Daudi cells compared to CD22−ve Jurkat cells. The route of uptake was a clathrin- and caveolin-independent pathway. Intracellular localization of the liposomes was in the endolysosomes. Upon drug release, apoptotic pathways were activated partly by the regulation of apoptotic and oncoproteins such as caspase-3 and c-myc. It was observed that the CD22 targeted drug delivery system was more potent and specific compared to other untargeted formulations.

  9. Local Gene Delivery System by Bubble Liposomes and Ultrasound Exposure into Joint Synovium

    Directory of Open Access Journals (Sweden)

    Yoichi Negishi

    2011-01-01

    Full Text Available Recently, we have developed novel polyethylene glycol modified liposomes (bubble liposomes; BL entrapping an ultrasound (US imaging gas, which can work as a gene delivery tool with US exposure. In this study, we investigated the usefulness of US-mediated gene transfer systems with BL into synoviocytes in vitro and joint synovium in vivo. Highly efficient gene transfer could be achieved in the cultured primary synoviocytes transfected with the combination of BL and US exposure, compared to treatment with plasmid DNA (pDNA alone, pDNA plus BL, or pDNA plus US. When BL was injected into the knee joints of mice, and US exposure was applied transcutaneously to the injection site, highly efficient gene expression could be observed in the knee joint transfected with the combination of BL and US exposure, compared to treatment with pDNA alone, pDNA plus BL, or pDNA plus US. The localized and prolonged gene expression was also shown by an in vivo luciferase imaging system. Thus, this local gene delivery system into joint synovium using the combination of BL and US exposure may be an effective means for gene therapy in joint disorders.

  10. Potential effect of cationic liposomes on interactions with oral bacterial cells and biofilms.

    Science.gov (United States)

    Sugano, Marika; Morisaki, Hirobumi; Negishi, Yoichi; Endo-Takahashi, Yoko; Kuwata, Hirotaka; Miyazaki, Takashi; Yamamoto, Matsuo

    2016-01-01

    Although oral infectious diseases have been attributed to bacteria, drug treatments remain ineffective because bacteria and their products exist as biofilms. Cationic liposomes have been suggested to electrostatically interact with the negative charge on the bacterial surface, thereby improving the effects of conventional drug therapies. However, the electrostatic interaction between oral bacteria and cationic liposomes has not yet been examined in detail. The aim of the present study was to examine the behavior of cationic liposomes and Streptococcus mutans in planktonic cells and biofilms. Liposomes with or without cationic lipid were prepared using a reverse-phase evaporation method. The zeta potentials of conventional liposomes (without cationic lipid) and cationic liposomes were -13 and 8 mV, respectively, and both had a mean particle size of approximately 180 nm. We first assessed the interaction between liposomes and planktonic bacterial cells with a flow cytometer. We then used a surface plasmon resonance method to examine the binding of liposomes to biofilms. We confirmed the binding behavior of liposomes with biofilms using confocal laser scanning microscopy. The interactions between cationic liposomes and S. mutans cells and biofilms were stronger than those of conventional liposomes. Microscopic observations revealed that many cationic liposomes interacted with the bacterial mass and penetrated the deep layers of biofilms. In this study, we demonstrated that cationic liposomes had higher affinity not only to oral bacterial cells, but also biofilms than conventional liposomes. This electrostatic interaction may be useful as a potential drug delivery system to biofilms.

  11. Single cell targeting using plasmon resonant gold-coated liposomes

    Science.gov (United States)

    Leung, Sarah J.; Romanowski, Marek

    2012-03-01

    We have developed an experimental system with the potential for the delivery and localized release of an encapsulated agent with high spatial and temporal resolution. We previously introduced liposome-supported plasmon resonant gold nanoshells; in this composite structure, the liposome allows for the encapsulation of substances, such as therapeutic agents, neurotransmitters, or growth factors, and the plasmon resonant structure facilitates the rapid release of encapsulated contents upon laser light illumination. More recently, we demonstrated that these gold-coated liposomes are capable of releasing their contents in a spectrally-controlled manner, where plasmon resonant nanoparticles only release content upon illumination with a wavelength of light matching their plasmon resonance band. We now show that this release mechanism can be used in a biological setting to deliver a peptide derivative of cholecystokinin to HEK293 cells overexpressing the CCK2 receptor. Using directed laser light, we may enable localized release from gold-coated liposomes to enable accurate perturbation of cellular functions in response to released compounds; this system may have possible applications in signaling pathways and drug discovery.

  12. Receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient delivery system for MRTF silencing in conjunctival fibrosis.

    Science.gov (United States)

    Yu-Wai-Man, Cynthia; Tagalakis, Aristides D; Manunta, Maria D; Hart, Stephen L; Khaw, Peng T

    2016-02-24

    There is increasing evidence that the Myocardin-related transcription factor/Serum response factor (MRTF/SRF) pathway plays a key role in fibroblast activation and that knocking down MRTF can lead to reduced scarring and fibrosis. Here, we have developed a receptor-targeted liposome-peptide-siRNA nanoparticle as a non-viral delivery system for MRTF-B siRNA in conjunctival fibrosis. Using 50 nM siRNA, the MRTF-B gene was efficiently silenced by 76% and 72% with LYR and LER nanoparticles, respectively. The silencing efficiency was low when non-targeting peptides or siRNA alone or liposome-siRNA alone were used. LYR and LER nanoparticles also showed higher silencing efficiency than PEGylated LYR-P and LER-P nanoparticles. The nanoparticles were not cytotoxic using different liposomes, targeting peptides, and 50 nM siRNA. Three-dimensional fibroblast-populated collagen matrices were also used as a functional assay to measure contraction in vitro, and showed that MRTF-B LYR nanoparticles completely blocked matrix contraction after a single transfection treatment. In conclusion, this is the first study to develop and show that receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient and safe non-viral siRNA delivery system that could be used to prevent fibrosis after glaucoma filtration surgery and other contractile scarring conditions in the eye.

  13. Liposomal Doxorubicin in the Treatment of Breast Cancer Patients: A Review

    Directory of Open Access Journals (Sweden)

    Juan Lao

    2013-01-01

    Full Text Available Drug delivery systems can provide enhanced efficacy and/or reduced toxicity for anticancer agents. Liposome drug delivery systems are able to modify the pharmacokinetics and biodistribution of cytostatic agents, increasing the concentration of the drug released to neoplastic tissue and reducing the exposure of normal tissue. Anthracyclines are a key drug in the treatment of both metastatic and early breast cancer, but one of their major limitations is cardiotoxicity. One of the strategies designed to minimize this side effect is liposome encapsulation. Liposomal anthracyclines have achieved highly efficient drug encapsulation and they have proven to be effective and with reduced cardiotoxicity, as a single agent or in combination with other drugs for the treatment of either anthracyclines-treated or naïve metastatic breast cancer patients. Of particular interest is the use of the combination of liposomal anthracyclines and trastuzumab in patients with HER2-overexpressing breast cancer. In this paper, we discuss the different studies on liposomal doxorubicin in metastatic and early breast cancer therapy.

  14. pH-sensitive liposomes: characterization and application

    International Nuclear Information System (INIS)

    Connor, J.

    1986-01-01

    It has been demonstrated that liposomes composed of dioleoylphosphatidylethanolamine (DOPE) and palmitoylhomocysteine (PHC) have the ability to fuse with adjacent membranes upon exposure to mildly acid pH. The ability of liposomes to fuse is absolutely dependent on the presence of DOPE and a weakly acidic amphiphile. The acid induced fusion event is a leaky process, but the leakage can be reduced by 50%, with only a small loss of fusion ability, by the inclusion of 40 mole percent cholesterol. Using an established monoclonal antibody targeting system. pH-sensitive immunoliposomes were prepared which successfully delivered entrapped calcein to the cytoplasm of target cells. The addition of chloroquine, which raises the internal pH of cellular vacuoles, blocks the cytoplasmic delivery of the pH-sensitive immunoliposomes. pH-insensitive immunoliposomes delivered calcein only to the endosome/lysosome system and not the cytoplasm. 31 P-NMR and light scattering of DOPE:OA liposomes under acidic conditions demonstrate that the effect of the protons and the divalent cations is to force the DOPE to revert to the hexagonal II configuration. In vivo experiments with DOPE:OA immunoliposomes indicate that the liposomes rapidly aggregate and release their contents upon exposure to plasma. These results indicate that pH-sensitive immunoliposomes are an effective tool for in vitro cytoplasmic delivery but are ineffective for in vivo delivery at this point in development

  15. Augmentation of antigen-specific immune responses using DNA-fusogenic liposome vaccine

    International Nuclear Information System (INIS)

    Yoshikawa, Tomoaki; Imazu, Susumu; Gao Jianqing; Hayashi, Kazuyuki; Tsuda, Yasuhiro; Shimokawa, Mariko; Sugita, Toshiki; Niwa, Takako; Oda, Atushi; Akashi, Mitsuru; Tsutsumi, Yasuo; Mayumi, Tadanori; Nakagawa, Shinsaku

    2004-01-01

    In an attempt to enhance the immunological efficacy of genetic immunization, we investigated a new biological means for delivering antigen gene directly to the cytoplasm via membrane fusion. In this context, we investigated fusogenic liposome (FL) encapsulating DNA as a possible genetic immunization vehicle. RT-PCR analysis indicated that a FL could introduce and express encapsulating OVA gene efficiently and rapidly in vitro. Consistent with this observation, an in vitro assay showed that FL-mediated antigen-gene delivery can induce potent presentation of antigen via the MHC class I-dependent pathway. Accordingly, immunization with FL containing the OVA-gene induced potent OVA-specific Th1 and Th2 cytokine production. Additionally, OVA-specific CTL responses and antibody production were also observed in systemic compartments including the spleen, upon immunization with the OVA-gene encapsulating FL. These findings suggest that FL is an effective genetic immunization carrier system for the stimulation of antigen-specific immune responses against its encoding antigen

  16. Gamma-ray-induced polymerization of mixed liposomes consisting of 2,4-octadecadienoyl groups of phospholipids and unpolymerizable components

    Energy Technology Data Exchange (ETDEWEB)

    Akama, Kazuhiro; Awai, Kouji; Yano, Yoshihiro; Tokuyama, Satoru; Nakano, Yoshio [Tsukuba Research Laboratory, NOF Corporation, Tsukuba, Ibaraki (Japan); Hosoi, Fumio; Omichi, Hideki [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    2000-06-01

    We studied the {gamma}-ray-induced polymerization of two mixed-liposome systems containing 1,2-bis-[(2E,4E)-octadecadienoyl]-sn-glycero-3-phosphocholine (DODPC) to clarify its mechanism; (a) containing DODPC and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), or DODPC/DPPC liposome, and (b) containing DODPC, DPPC, Cholesterol (Chol), and stearic acid (SA), or DODPC/DPPC/Chol/SA liposomes was carried out. For each system, various molar ratios of DODPC/DPPC were studied. For DODPC/DPPC/Chol/SA liposomes, the molar ratio of phospholipid/Chol/SA was 7/7/2. Liposomes were prepared by extrusion through a 0.2-{mu}m-pore polycarbonate filter and polymerized by {gamma}-irradiation at a dose rate of 3.3 kGy/h at 4degC. Polymerization rate increased when DODPC/DPPC was 5/5 in DODPC/DPPC liposomes and when it was 9/1, 8/2, 7/3, and 5/5 in DODPC/DPPC/Chol/SA liposomes. The degree of polymerization at molar ratio 5/5 for each mixed-liposome system significantly increased compared with that of DODPC liposomes containing no DPPC. For polymerized mixed liposomes stability, mean diameter after one freeze-thaw cycle remained unchanged for molar ratios from 10/0 to 8/2 of either DODPC/DPPC or DODPC/DPPC/Chol/SA liposomes. {gamma}-Ray-induced polymerization of each mixed-liposome system was analyzed using kinetic treatment of polymerization. Although the rate of polymerization for either systems differed from that of DODPC liposomes, the polymerization mechanism was the same. Immiscibility between DODPC and unpolymerizable components was estimated based on the kinetic data of polymerization. Hydrophobic interactions of DPPC and/or Chol with DODPC significantly affected the conformation of DODPC, which rearranges into an easily polymerizable conformation. The rate and degree of polymerization thus increased. (author)

  17. Estimating Motor Carrier Management Information System Crash File Underreporting from Carrier Records.

    Science.gov (United States)

    2017-08-01

    This FMCSA-sponsored research investigated the claim that motor carriers have a substantial number of crashes in their own records that are not contained in the Motor Carrier Management Information System (MCMIS) crash file. Based on the results of t...

  18. Liposomal α-galactosylceramide is taken up by gut-associated lymphoid tissue and stimulates local and systemic immune responses.

    Science.gov (United States)

    Kaneko, Kan; McDowell, Arlene; Ishii, Yasuyuki; Hook, Sarah

    2017-12-01

    α-Galactosylceramide (α-GalCer), a synthetic glycosphingolipid that exhibits potent immunostimulatory effects through activation of natural killer T (NKT) cells, can be used to treat conditions such as atopy, cancer, infection and autoimmunity. Administration of therapeutics through the oral route has advantages such as patient convenience, safety and reduced cost; however, there has been little research to investigate whether oral delivery of α-GalCer is possible. The aim of this study was therefore to determine whether α-GalCer formulated in either DMSO/Tween 80 or in liposomes, could access lymphoid tissue and stimulate immune activation following oral administration. Fluorescently labelled cationic liposomes incorporating α-GalCer were prepared, characterized and administered by oral gavage to fasted mice. Liposomes were detected inside the Peyer's patches (PPs), in the subepithelial dome just under the follicle-associated epithelium. CD11b + cells and CD11c + were shown to have taken up the formulation in a higher proportion compared to the total cell proportion in the PPs, suggesting that cells with these markers may be the prominent antigen-presenting cells involved in selective uptake. Finally, the liposomal formulation demonstrated a higher degree of immune stimulation compared to the DMSO/Tween 80 solubilized α-GalCer in the PPs, mesenteric lymph nodes and spleen as shown by the increased expression of IL-4 mRNA expression and increased proportion of NKT cells at 6 h and 3 days after administration. These results show that oral delivery of a liposomal α-GalCer can stimulate local and systemic immune responses to a different degree compared to the non-liposomal form. © 2017 Royal Pharmaceutical Society.

  19. Therapeutic efficacy of liposome-encapsulated gentamicin in rat Klebsiella pneumoniae pneumonia in relation to impaired host defense and low bacterial susceptibility to gentamicin.

    NARCIS (Netherlands)

    R.M. Schiffelers (Raymond); G. Storm (Gert); M.T. ten Kate (Marian); I.A.J.M. Bakker-Woudenberg (Irma)

    2001-01-01

    textabstractLong-circulating liposomes (LCL) may be used as targeted antimicrobial drug carriers as they localize at sites of infection. As a result, LCL-encapsulated gentamicin (LE-GEN) has demonstrated superior antibacterial activity over the free drug in a

  20. Octanol-assisted liposome assembly on chip

    NARCIS (Netherlands)

    Deshpande, S.R.; Caspi, Y.; Meijering, A.E.C.; Dekker, C.

    2016-01-01

    Liposomes are versatile supramolecular assemblies widely used in basic and applied sciences. Here we present a novel microfluidics-based method, octanol-assisted liposome assembly (OLA), to form monodisperse, cell-sized (5–20 μm), unilamellar liposomes with excellent encapsulation efficiency. Akin

  1. Boronated liposome development and evaluation

    International Nuclear Information System (INIS)

    Hawthorne, M.F.

    1995-01-01

    The boronated liposome development and evaluation effort consists of two separate tasks. The first is the development of new boron compounds and the synthesis of known boron species with BNCT potential. These compounds are then encapsulated within liposomes for the second task, biodistribution testing in tumor-bearing mice, which examines the potential for the liposomes and their contents to concentrate boron in cancerous tissues

  2. Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy

    Directory of Open Access Journals (Sweden)

    Han-Chung Wu

    2010-01-01

    Full Text Available Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

  3. Advances in nanotechnology-based carrier systems for targeted delivery of bioactive drug molecules with special emphasis on immunotherapy in drug resistant tuberculosis - a critical review.

    Science.gov (United States)

    Singh, Jagdeep; Garg, Tarun; Rath, Goutam; Goyal, Amit K

    2016-06-01

    From the early sixteenth and seventeenth centuries to the present day of life, tuberculosis (TB) still is a global health threat with some new emergence of resistance. This type of emergence poses a vital challenge to control TB cases across the world. Mortality and morbidity rates are high due to this new face of TB. The newer nanotechnology-based drug-delivery approaches involving micro-metric and nano-metric carriers are much needed at this stage. These delivery systems would provide more advantages over conventional systems of treatment by producing enhanced therapeutic efficacy, uniform distribution of drug molecule to the target site, sustained and controlled release of drug molecules and lesser side effects. The main aim to develop these novel drug-delivery systems is to improve the patient compliance and reduce therapy time. This article reviews and elaborates the new concepts and drug-delivery approaches for the treatment of TB involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro and nanoemulsion) and some other novel drug-delivery systems for the effective treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for management of MDR-TB and XDR-TB.

  4. Rescuing apoptotic neurons in Alzheimer’s disease using wheat germ agglutinin-conjugated and cardiolipin-conjugated liposomes with encapsulated nerve growth factor and curcumin

    Directory of Open Access Journals (Sweden)

    Kuo YC

    2015-04-01

    Full Text Available Yung-Chih Kuo, Ching-Chun Lin Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan, Republic of China Abstract: Liposomes with cardiolipin (CL and wheat germ agglutinin (WGA were developed to permeate the blood–brain barrier and treat Alzheimer’s disease. WGA-conjugated and CL-incorporated liposomes (WGA-CL-liposomes were used to transport nerve growth factor (NGF and curcumin (CUR across a monolayer of human brain-microvascular endothelial cells regulated by human astrocytes and to protect SK-N-MC cells against apoptosis induced by ß-amyloid1–42 (Aß1–42 fibrils. An increase in the CL mole percentage in lipids increased the liposomal diameter, absolute zeta potential value, entrapment efficiency of NGF and CUR, release of NGF, biocompatibility, and viability of SK-N-MC cells with Aß1–42, but decreased the atomic ratio of nitrogen to phosphorus and release of CUR. In addition, an increase in the WGA concentration for grafting enhanced the liposomal diameter, atomic ratio of nitrogen to phosphorus, and permeability of NGF and CUR across the blood–brain barrier, but reduced the absolute zeta potential value and biocompatibility. WGA-CL-liposomes carrying NGF and CUR could be promising colloidal delivery carriers for future clinical application in targeting the blood–brain barrier and inhibiting neurotoxicity. Keywords: Alzheimer’s disease, nerve growth factor, curcumin, wheat germ agglutinin, cardiolipin, liposome

  5. Polyion-induced aggregation of oppositely charged liposomes and charged colloidal particles: the many facets of complex formation in low-density colloidal systems.

    Science.gov (United States)

    Cametti, C

    2008-10-01

    system, governed by a balance between long-range electrostatic repulsion and short-range attraction, resulting in relatively large, equilibrium clusters, whose size and overall charge can be continuously tunable by simple environmental parameters. These structures present a variety of behaviors with a not yet completely understood phenomenology. On the other hand, the resulting structures possess some peculiar properties that justify their employment as drug delivery systems. Bio-compatibility, stability and ability to deliver various bio-active molecules and, moreover, their environmental responsiveness make liposome-based clusters a versatile carrier, with possibility of efficient targeting to different organs and tissues. Among the different structures made possible by the aggregating mechanism (cationic particles stuck together by anionic polyions or conversely anionic particles stuck together by cationic polyions), I will review the main experimental evidences for the existence of cationic liposome clusters. Especial attention is paid to our own work, mainly aimed at the characterization of these novel structures from a physical point of view.

  6. Comparison of the cellular transport mechanism of cationic, star-shaped polymers and liposomes in HaCat cells

    Directory of Open Access Journals (Sweden)

    Luo H

    2017-02-01

    Full Text Available Heng-Cong Luo,1,2,* Na Li,1,* Li Yan,1 Kai-jin Mai,3 Kan Sun,1 Wei Wang,1 Guo-Juan Lao,1 Chuan Yang,1 Li-Ming Zhang,3 Meng Ren1 1Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Medical Research Center, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Endocrinology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 3School of Materials Science and Engineering, School of Chemistry, Sun Yat-Sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Several biological barriers must be overcome to achieve efficient nonviral gene delivery. These barriers include target cell uptake, lysosomal degradation, and dissociation from the carrier. In this study, we compared the differences in the uptake mechanism of cationic, star-shaped polymer/MMP-9siRNA complexes (β-CD-(D37/MMP-9siRNA complexes: polyplexes and commercial liposome/MMP-9siRNA complexes (Lipofectamine® 2000/MMP-9siRNA complexes: liposomes. The uptake pathway and transfection efficiency of the polyplexes and liposomes were determined by fluorescence microscopy, flow cytometry, and reverse transcriptase-polymerase chain reaction. The occurrence of intracellular processing was assessed by confocal laser scanning microscopy. Endosomal acidification inhibitors were used to explore the endosomal escape mechanisms of the polyplexes and lysosomes. We concluded that the polyplexes were internalized by non-caveolae- and non-clathrin-mediated pathways, with no lysosomal trafficking, thereby inducing successful transfection, while the majority of liposomes were internalized by clathrin-dependent endocytosis (CDE, caveolae-mediated endocytosis, and macropinocytosis, and only CDE induced successful transfection. Liposomes might escape more quickly than polyplexes, and

  7. Evaluation of Extrusion Technique for Nanosizing Liposomes

    Directory of Open Access Journals (Sweden)

    Sandy Gim Ming Ong

    2016-12-01

    Full Text Available The aim of the present study was to study the efficiency of different techniques used for nanosizing liposomes. Further, the aim was also to evaluate the effect of process parameters of extrusion techniques used for nanosizing liposomes on the size and size distribution of the resultant liposomes. To compare the efficiency of different nanosizing techniques, the following techniques were used to nanosize the liposomes: extrusion, ultrasonication, freeze-thaw sonication (FTS, sonication and homogenization. The extrusion technique was found to be the most efficient, followed by FTS, ultrasonication, sonication and homogenization. The extruder used in the present study was fabricated using readily available and relatively inexpensive apparatus. Process parameters were varied in extrusion technique to study their effect on the size and size distribution of extruded liposomes. The results obtained indicated that increase in the flow rate of the extrusion process decreased the size of extruded liposomes however the size homogeneity was negatively impacted. Furthermore, the liposome size and distribution was found to decline with decreasing membrane pore size. It was found that by extruding through a filter with a pore size of 0.2 µm and above, the liposomes produced were smaller than the pore size, whereas, when they were extruded through a filter with a pore size of less than 0.2 µm the resultant liposomes were slightly bigger than the nominal pore size. Besides that, increment of extrusion temperature above transition temperature of the pro-liposome had no effect on the size and size distribution of the extruded liposomes. In conclusion, the extrusion technique was reproducible and effective among all the methods evaluated. Furthermore, processing parameters used in extrusion technique would affect the size and size distribution of liposomes. Therefore, the process parameters need to be optimized to obtain a desirable size range and homogeneity

  8. Activation of the human complement system by cholesterol-rich and pegylated liposomes - Modulation of cholesterol-rich liposome-mediated complement activation by elevated serum LDL and HDL levels

    DEFF Research Database (Denmark)

    Moghimi, S.M.; Hamad, I.; Bunger, R.

    2006-01-01

    level of S-protein-bound form of the terminal complex (SC5b-9). However, liposome-induced rise of SC5b-9 was significantly suppressed when serum HDL cholesterol levels increased by 30%. Increase of serum LDL to levels similar to that observed in heterozygous familial hypercholesterolemia also suppressed......Intravenously infused liposomes may induce cardiopulmonary distress in some human subjects, which is a manifestation of "complement activation-related pseudoallergy." We have now examined liposome-mediated complement activation in human sera with elevated lipoprotein (LDL and HDL) levels, since...... abnormal or racial differences in serum lipid profiles seem to modulate the extent of complement activation and associated adverse responses. In accordance with our earlier observations, cholesterol-rich (45 mol% cholesterol) liposomes activated human complement, as reflected by a significant rise in serum...

  9. Preparation and properties of functional mixed-lipid liposomes by γ-ray irradiation

    International Nuclear Information System (INIS)

    Hosoi, Fumio; Omichi, Hideki; Akama, Kazuhiro; Awai, Kouji; Yano, Yoshihiro; Nakano, Yoshio

    1998-01-01

    The feature of mixed-lipid liposomes such as polymerization and polymerized liposomes stability were investigated to find means for producing red cells containing hemoglobin inside the liposomes. The surface pressure-area isotherm values of the mixed-lipid monolayer indicated 1-stearoyl-2-(2,4-octadecadienoyl)-glycero-3-phosphocholine (SOPC) to be immiscible in cholesterol (Chol) and stearic acid (SA), and each component to contain separate domains in the bilayer membrane of liposomes. Radiation induced polymerization of mixed-SOPC liposomes was carried out using γ-rays from 60 Co at 4degC to stabilize lipid bilayers. The polymer yield increased significantly by adding Chol and SA to SOPC. The rate of polymerization of SOPC liposomes increased linearly with increasing of dose rate. The molecular weight of the polymer decreased with an increase in irradiation time. Irradiated SOPC/Chol/SA liposome vesicle size was affected by freeze-thawing. The vesicle size did not change when SOPC/Chol/SA was present in the system due to the addition of immiscible saturated 1,2-dipalmitoyl-glycero-3-phosphocholine (DPPC). (author)

  10. Lymphatic uptake and biodistribution of liposomes after subcutaneous injection - IV. Fate of liposomes in regional lymph nodes

    NARCIS (Netherlands)

    Oussoren, C; Scherphof, G; van der Want, JJ; van Rooijen, N; Storm, G

    1998-01-01

    The ability of clodronate-containing liposomes to deplete lymph nodes of macrophages was used as a tool to investigate the fate of liposomes in regional lymph nodes after subcutaneous (s.c.) administration. Reduced lymph node localization of liposomes in macrophage-depleted lymph nodes confirmed

  11. Effect of incorporating cholesterol into DDA:TDB liposomal adjuvants on bilayer properties, biodistribution, and immune responses.

    Science.gov (United States)

    Kaur, Randip; Henriksen-Lacey, Malou; Wilkhu, Jitinder; Devitt, Andrew; Christensen, Dennis; Perrie, Yvonne

    2014-01-06

    Cholesterol is an abundant component of mammalian cell membranes and has been extensively studied as an artificial membrane stabilizer in a wide range of phospholipid liposome systems. In this study, the aim was to investigate the role of cholesterol in cationic liposomal adjuvant system based on dimethyldioctadecylammonium (DDA) and trehalose 6,6'-dibehenate (TDB) which has been shown as a strong adjuvant system for vaccines against a wide range of diseases. Packaging of cholesterol within DDA:TDB liposomes was investigated using differential scanning calorimetery and surface pressure-area isotherms of lipid monolayers; incorporation of cholesterol into liposomal membranes promoted the formation of a liquid-condensed monolayer and removed the main phase transition temperature of the system, resulting in an increased bilayer fluidity and reduced antigen retention in vitro. In vivo biodistribution studies found that this increase in membrane fluidity did not alter deposition of liposomes and antigen at the site of injection. In terms of immune responses, early (12 days after immunization) IgG responses were reduced by inclusion of cholesterol; thereafter there were no differences in antibody (IgG, IgG1, IgG2b) responses promoted by DDA:TDB liposomes with and without cholesterol. However, significantly higher levels of IFN-gamma were induced by DDA:TDB liposomes, and liposome uptake by macrophages in vitro was also shown to be higher for DDA:TDB liposomes compared to their cholesterol-containing counterparts, suggesting that small changes in bilayer mechanics can impact both cellular interactions and immune responses.

  12. Integrin Targeting and Toxicological Assessment of Peptide-Conjugated Liposome Delivery Systems to Activated Endothelial Cells

    DEFF Research Database (Denmark)

    Kermanizadeh, Ali; Villadsen, Klaus; Østrem, Ragnhild Garborg

    2017-01-01

    constructed with the aim of targeting integrins (i.e. vitronectin and/or fibronectin receptors) on activated endothelial cells. The peptide-conjugated liposomes induced only cytotoxicity at the highest concentration in non-activated or activated endothelial cells, as well as in co-culture of endothelial cells...... and macrophages. There was unaltered secretion of cytokines following exposure of peptide-conjugated liposomes to endothelial cells, indicating that the materials were not inflammogenic. Liposomes with a peptide targeting the fibronectin receptor (integrin α5β1) were more effective in targeting of activated....... Therefore, this study demonstrates the feasibility of constructing a peptide-conjugated cationic liposome, which displays targeting to activated endothelial cells at concentrations that are not cytotoxic or inflammogenic to the cells....

  13. Preparation and ocular pharmacokinetics of ganciclovir liposomes.

    Science.gov (United States)

    Shen, Yan; Tu, Jiasheng

    2007-12-07

    Ophthalmic liposomes of ganciclovir (GCV) were prepared by the reverse phase evaporation method, and their ocular pharmacokinetics in albino rabbits were compared with those obtained after dosing with GCV solution. The in vitro transcorneal permeability of GCV liposomes was found to be 3.9-fold higher than that of the solution. After in vivo instillation in albino rabbits, no difference was found in the precorneal elimination rate of GCV from liposome vs solution dosing. The aqueous humor concentration-time profiles of both liposomes and solution were well described by 2-compartmental pharmacokinetics with first-order absorption. The area under the curve of the aqueous humor concentration-time profiles of GCV liposomes was found to be 1.7-fold higher than that of GCV solution. Ocular tissue distribution of GCV from liposomes was 2 to 10 times higher in the sclera, cornea, iris, lens, and vitreous humor when compared with those observed after solution dosing. These results suggested that liposomes may hold some promise in ocular GCV delivery.

  14. Dual-coating of liposomes as encapsulating matrix of antimicrobial peptides: Development and characterization

    Science.gov (United States)

    Gomaa, Ahmed I.; Martinent, Cynthia; Hammami, Riadh; Fliss, Ismail; Subirade, Muriel

    2017-11-01

    Abstract Antimicrobial peptides have been proposed as a potential biopreservatives in pharmaceutical research and agribusiness. However, many limitations hinder their utilization, such as their vulnerability to proteolytic digestion and their potential interaction with other food ingredients in complex food systems. One approach to overcome such problems is developing formulations entrapping and thereby protecting the antimicrobial peptides. Liposome encapsulation is a strategy that could be implemented to combine protection of the antimicrobial activity of the peptides from proteolytic enzymes and the controlled release of the encapsulated active ingredients. The objective of this study was to develop dual-coated food grade liposome formulations for oral administration of bacteriocins. The formulations were developed from anionic and cationic phospholipids as models of negatively and positively charged liposomes, respectively. Liposomes were prepared by the hydration of lipid films. Subsequently, the liposomes were coated with two layers comprising a biopolymer network (pectin) and whey proteins (WPI) in order to further improve their stability and enable the gradual release of the developed liposomes. Liposomes were characterized for their size, charge, molecular structure, morphology, encapsulation efficiency and release. The results of FTIR, zeta potential, size distribution and transmission electron microscopy confirmed that the liposomes were efficiently coated. Ionic interactions were involved in the stabilization of the positively charged liposome formulations. Negatively charge liposome formulations were stabilized through weak interactions. The release study proved the efficiency of dual coating on the protection of liposomes against gastrointestinal digestion. This work is the first to study the encapsulation of antimicrobial peptides in dual-coated liposomes. Furthermore, the work successfully encapsulated MccJ25 in both negative and positive liposome

  15. Ultrasound, liposomes, and drug delivery: principles for using ultrasound to control the release of drugs from liposomes.

    Science.gov (United States)

    Schroeder, Avi; Kost, Joseph; Barenholz, Yechezkel

    2009-11-01

    Ultrasound is used in many medical applications, such as imaging, blood flow analysis, dentistry, liposuction, tumor and fibroid ablation, and kidney stone disruption. In the past, low frequency ultrasound (LFUS) was the main method to downsize multilamellar (micron range) vesicles into small (nano scale) unilamellar vesicles. Recently, the ability of ultrasound to induce localized and controlled drug release from liposomes, utilizing thermal and/or mechanical effects, has been shown. This review, deals with the interaction of ultrasound with liposomes, focusing mainly on the mechanical mechanism of drug release from liposomes using LFUS. The effects of liposome lipid composition and physicochemical properties, on one hand, and of LFUS parameters, on the other, on liposomal drug release, are addressed. Acoustic cavitation, in which gas bubbles oscillate and collapse in the medium, thereby introducing intense mechanical strains, increases release substantially. We suggest that the mechanism of release may involve formation and collapse of small gas nuclei in the hydrophobic region of the lipid bilayer during exposure to LFUS, thereby inducing the formation of transient pores through which drugs are released. Introducing PEG-lipopolymers to the liposome bilayer enhances responsivity to LFUS, most likely due to absorption of ultrasonic energy by the highly hydrated PEG headgroups. The presence of amphiphiles, such as phospholipids with unsaturated acyl chains, which destabilize the lipid bilayer, also increases liposome susceptibility to LFUS. Application of these principles to design highly LFUS-responsive liposomes is discussed.

  16. Lipid conjugated prodrugs for enzyme-triggered liposomal drug delivery to tumors

    DEFF Research Database (Denmark)

    Clausen, Mads Hartvig

    2011-01-01

    For some time we have been developing novel enzyme-triggered prodrugs for drug delivery targeting cancer. The liposomal prodrugs take advantage of the EPR effect to localize to tumors and of the local over-expression of secretory phospholipase A2 in tumors. Compared to conventional liposomal drug...... delivery systems, our prodrug-lipid conjugates have two main advantages: 1) the drugs are covalently linked to the lipids and thus leakage is circumvented and 2) the lipophilic bilayer of the formulated liposomes effectively shields the drugs from the aqueous environment in vivo. Consequently, the strategy...... targeting nuclear receptors and structural proteins. The presentation will highlight various strategies and recent progress towards improved systems, including chemical synthesis, enzyme activity and cytotoxicity....

  17. Lipossomas e suas aplicações terapêuticas: estado da arte Liposomes and their therapeutic: state of art applications

    Directory of Open Access Journals (Sweden)

    Cinthia Meireles Batista

    2007-06-01

    Full Text Available Lipossomas são vesículas constituídas de uma ou mais bicamadas fosfolipídicas orientadas concentricamente em torno de um compartimento aquoso e servem como carreadores de fármacos, biomoléculas ou agentes de diagnóstico. A estabilidade dos lipossomas pode ser afetada por fatores químicos, físicos e biológicos. Após administração intravenosa, lipossomas convencionais são rapidamente capturados pelo sistema fagocitário mononuclear. Para evitar essa captura, lipossomas furtivos foram desenvolvidos, os quais apresentam a superfície modificada com componentes hidrofílicos. Para permitir a liberação seletiva do fármaco nos sítios alvos, ligantes de reconhecimento específico são conjugados na superfície de lipossomas. Em geral, os métodos de preparação de lipossomas incluem hidratação de um filme lipídico seguida de sonicação ou extrusão para redução do tamanho das vesículas. Os lipossomas são caracterizados quanto ao tamanho e composição química das vesículas e conteúdo do material encapsulado. Nesta revisão, constata-se que os lipossomas oferecem maior eficácia e segurança com relação aos tratamentos convencionais. Apesar de algumas formulações lipossomais serem comercializadas desde os anos 1980 para tratamento de infecções fúngicas sistêmicas e do câncer, problemas de ordem tecnológica e biológica fazem com que os lipossomas sejam ainda extensivamente estudados para desenvolvimento de formulações estáveis no organismo visando à terapia de várias doenças, principalmente do câncer.Liposomes are vesicles that consist of one or more concentric phospholipidic bilayers organized around an aqueous inner compartment. They are carriers of drugs, biomolecules and diagnostic agents. The stability of liposomes can be influenced by chemical or physical factors. Once injected in the circulatory system, conventional liposomes suffer uptake by the mononuclear phagocytic system. To avoid such a capture

  18. Modeling the Release Kinetics of Poorly Water-Soluble Drug Molecules from Liposomal Nanocarriers

    Directory of Open Access Journals (Sweden)

    Stephan Loew

    2011-01-01

    Full Text Available Liposomes are frequently used as pharmaceutical nanocarriers to deliver poorly water-soluble drugs such as temoporfin, cyclosporine A, amphotericin B, and paclitaxel to their target site. Optimal drug delivery depends on understanding the release kinetics of the drug molecules from the host liposomes during the journey to the target site and at the target site. Transfer of drugs in model systems consisting of donor liposomes and acceptor liposomes is known from experimental work to typically exhibit a first-order kinetics with a simple exponential behavior. In some cases, a fast component in the initial transfer is present, in other cases the transfer is sigmoidal. We present and analyze a theoretical model for the transfer that accounts for two physical mechanisms, collisions between liposomes and diffusion of the drug molecules through the aqueous phase. Starting with the detailed distribution of drug molecules among the individual liposomes, we specify the conditions that lead to an apparent first-order kinetic behavior. We also discuss possible implications on the transfer kinetics of (1 high drug loading of donor liposomes, (2 attractive interactions between drug molecules within the liposomes, and (3 slow transfer of drugs between the inner and outer leaflets of the liposomes.

  19. Reversible Morphological Control of Tubulin-Encapsulating Giant Liposomes by Hydrostatic Pressure.

    Science.gov (United States)

    Hayashi, Masahito; Nishiyama, Masayoshi; Kazayama, Yuki; Toyota, Taro; Harada, Yoshie; Takiguchi, Kingo

    2016-04-19

    Liposomes encapsulating cytoskeletons have drawn much recent attention to develop an artificial cell-like chemical-machinery; however, as far as we know, there has been no report showing isothermally reversible morphological changes of liposomes containing cytoskeletons because the sets of various regulatory factors, that is, their interacting proteins, are required to control the state of every reaction system of cytoskeletons. Here we focused on hydrostatic pressure to control the polymerization state of microtubules (MTs) within cell-sized giant liposomes (diameters ∼10 μm). MT is the cytoskeleton formed by the polymerization of tubulin, and cytoskeletal systems consisting of MTs are very dynamic and play many important roles in living cells, such as the morphogenesis of nerve cells and formation of the spindle apparatus during mitosis. Using real-time imaging with a high-pressure microscope, we examined the effects of hydrostatic pressure on the morphology of tubulin-encapsulating giant liposomes. At ambient pressure (0.1 MPa), many liposomes formed protrusions due to tubulin polymerization within them. When high pressure (60 MPa) was applied, the protrusions shrank within several tens of seconds. This process was repeatedly inducible (around three times), and after the pressure was released, the protrusions regenerated within several minutes. These deformation rates of the liposomes are close to the velocities of migrating or shape-changing living cells rather than the shortening and elongation rates of the single MTs, which have been previously measured. These results demonstrate that the elongation and shortening of protrusions of giant liposomes is repeatedly controllable by regulating the polymerization state of MTs within them by applying and releasing hydrostatic pressure.

  20. PLGA nanoparticles introduction into mitoxantrone-loaded ultrasound-responsive liposomes: In vitro and in vivo investigations.

    Science.gov (United States)

    Xin, Yuxuan; Qi, Qi; Mao, Zhenmin; Zhan, Xiaoping

    2017-08-07

    A novel ultrasound-responsive liposomal system for tumor targeting was prepared in order to increase the antitumor efficacy and decrease serious side effects. In this paper, PLGA nanoparticles were used ultrasound-responsive agents instead of conventional microbubbles. The PLGA-nanoparticles were prepared by an emulsion solvent evaporation method. The liposomes were prepared by a lipid film hydration method. Particle size, zeta potential, encapsulation efficiency and drug loading capacity of the liposomes were studied by light scattering analysis and dialysis. Transmission electron microscopy (TEM) and atomic force microscope (AFM) were used to investigate the morphology of liposomes. The release in vitro was carried out in the pH 7.4 phosphate buffer solutions, as a result, liposome L3 encapsulating PLGA-nanoparticles displayed good stability under simulative physiological conditions and quickly responsive release under the ultrasound. The release in vivo was carried out on the rats, as a result, liposome L3 showed higher bioavailability than traditional intravenous injectable administration, and liposome L3 showed higher elimination ratio after stimulation by ultrasound than L3 without stimulation. Thus, the novel ultrasound-responsive liposome encapsulating PLGA-nanoparticles has a potential to be developed as a new drug delivery system for anti-tumor drug. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. A Triple Co-Culture Model of the Human Respiratory Tract to Study Immune-Modulatory Effects of Liposomes and Virosomes.

    Directory of Open Access Journals (Sweden)

    Rebecca A M Blom

    Full Text Available The respiratory tract with its ease of access, vast surface area and dense network of antigen-presenting cells (APCs represents an ideal target for immune-modulation. Bio-mimetic nanocarriers such as virosomes may provide immunomodulatory properties to treat diseases such as allergic asthma. In our study we employed a triple co-culture model of epithelial cells, macrophages and dendritic cells to simulate the human airway barrier. The epithelial cell line 16HBE was grown on inserts and supplemented with human blood monocyte-derived macrophages (MDMs and dendritic cells (MDDCs for exposure to influenza virosomes and liposomes. Additionally, primary human nasal epithelial cells (PHNEC and EpCAM+ epithelial progenitor cell mono-cultures were utilized to simulate epithelium from large and smaller airways, respectively. To assess particle uptake and phenotype change, cell cultures were analyzed by flow cytometry and pro-inflammatory cytokine concentrations were measured by ELISA. All cell types internalized virosomes more efficiently than liposomes in both mono- and co-cultures. APCs like MDMs and MDDCs showed the highest uptake capacity. Virosome and liposome treatment caused a moderate degree of activation in MDDCs from mono-cultures and induced an increased cytokine production in co-cultures. In epithelial cells, virosome uptake was increased compared to liposomes in both mono- and co-cultures with EpCAM+ epithelial progenitor cells showing highest uptake capacity. In conclusion, all cell types successfully internalized both nanocarriers with virosomes being taken up by a higher proportion of cells and at a higher rate inducing limited activation of MDDCs. Thus virosomes may represent ideal carrier antigen systems to modulate mucosal immune responses in the respiratory tract without causing excessive inflammatory changes.

  2. Etoposide Incorporated into Camel Milk Phospholipids Liposomes Shows Increased Activity against Fibrosarcoma in a Mouse Model

    Directory of Open Access Journals (Sweden)

    Hamzah M. Maswadeh

    2015-01-01

    Full Text Available Phospholipids were isolated from camel milk and identified by using high performance liquid chromatography and gas chromatography-mass spectrometry (GC/MS. Anticancer drug etoposide (ETP was entrapped in liposomes, prepared from camel milk phospholipids, to determine its activity against fibrosarcoma in a murine model. Fibrosarcoma was induced in mice by injecting benzopyrene (BAP and tumor-bearing mice were treated with various formulations of etoposide, including etoposide entrapped camel milk phospholipids liposomes (ETP-Cam-liposomes and etoposide-loaded DPPC-liposomes (ETP-DPPC-liposomes. The tumor-bearing mice treated with ETP-Cam-liposomes showed slow progression of tumors and increased survival compared to free ETP or ETP-DPPC-liposomes. These results suggest that ETP-Cam-liposomes may prove to be a better drug delivery system for anticancer drugs.

  3. Phase-Separated Liposomes Enhance the Efficiency of Macromolecular Delivery to the Cellular Cytoplasm.

    Science.gov (United States)

    Imam, Zachary I; Kenyon, Laura E; Ashby, Grant; Nagib, Fatema; Mendicino, Morgan; Zhao, Chi; Gadok, Avinash K; Stachowiak, Jeanne C

    2017-10-01

    From viruses to organelles, fusion of biological membranes is used by diverse biological systems to deliver macromolecules across membrane barriers. Membrane fusion is also a potentially efficient mechanism for the delivery of macromolecular therapeutics to the cellular cytoplasm. However, a key shortcoming of existing fusogenic liposomal systems is that they are inefficient, requiring a high concentration of fusion-promoting lipids in order to cross cellular membrane barriers. Toward addressing this limitation, our experiments explore the extent to which membrane fusion can be amplified by using the process of lipid membrane phase separation to concentrate fusion-promoting lipids within distinct regions of the membrane surface. We used confocal fluorescence microscopy to investigate the integration of fusion-promoting lipids into a ternary lipid membrane system that separated into liquid-ordered and liquid-disordered membrane phases. Additionally, we quantified the impact of membrane phase separation on the efficiency with which liposomes transferred lipids and encapsulated macromolecules to cells, using a combination of confocal fluorescence imaging and flow cytometry. Here we report that concentrating fusion-promoting lipids within phase-separated lipid domains on the surfaces of liposomes significantly increases the efficiency of liposome fusion with model membranes and cells. In particular, membrane phase separation enhanced the delivery of lipids and model macromolecules to the cytoplasm of tumor cells by at least 4-fold in comparison to homogenous liposomes. Our findings demonstrate that phase separation can enhance membrane fusion by locally concentrating fusion-promoting lipids on the surface of liposomes. This work represents the first application of lipid membrane phase separation in the design of biomaterials-based delivery systems. Additionally, these results lay the ground work for developing fusogenic liposomes that are triggered by physical and

  4. Simultaneous quantification of tumor uptake for targeted and non-targeted liposomes and their encapsulated contents by ICP-MS

    Science.gov (United States)

    Cheng, Zhiliang; Zaki, Ajlan Al; Hui, James Z; Tsourkas, Andrew

    2012-01-01

    Liposomes are intensively being developed for biomedical applications including drug and gene delivery. However, targeted liposomal delivery in cancer treatment is a very complicated multi-step process. Unfavorable liposome biodistribution upon intravenous administration and membrane destabilization in blood circulation could result in only a very small fraction of cargo reaching the tumors. It would therefore be desirable to develop new quantitative strategies to track liposomal delivery systems to improve the therapeutic index and decrease systemic toxicity. Here, we developed a simple and non-radiative method to quantify the tumor uptake of targeted and non-targeted control liposomes as well as their encapsulated contents simultaneously. Specifically, four different chelated lanthanide metals were encapsulated or surface-conjugated onto tumor-targeted and non-targeted liposomes, respectively. The two liposome formulations were then injected into tumor-bearing mice simultaneously and their tumor delivery was determined quantitatively via inductively coupled plasma-mass spectroscopy (ICP-MS), allowing for direct comparisons. Tumor uptake of the liposomes themselves and their encapsulated contents were consistent with targeted and non-targeted liposome formulations that were injected individually. PMID:22882145

  5. Rapid Quantification and Validation of Lipid Concentrations within Liposomes

    Directory of Open Access Journals (Sweden)

    Carla B. Roces

    2016-09-01

    Full Text Available Quantification of the lipid content in liposomal adjuvants for subunit vaccine formulation is of extreme importance, since this concentration impacts both efficacy and stability. In this paper, we outline a high performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD method that allows for the rapid and simultaneous quantification of lipid concentrations within liposomal systems prepared by three liposomal manufacturing techniques (lipid film hydration, high shear mixing, and microfluidics. The ELSD system was used to quantify four lipids: 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC, cholesterol, dimethyldioctadecylammonium (DDA bromide, and ᴅ-(+-trehalose 6,6′-dibehenate (TDB. The developed method offers rapidity, high sensitivity, direct linearity, and a good consistency on the responses (R2 > 0.993 for the four lipids tested. The corresponding limit of detection (LOD and limit of quantification (LOQ were 0.11 and 0.36 mg/mL (DMPC, 0.02 and 0.80 mg/mL (cholesterol, 0.06 and 0.20 mg/mL (DDA, and 0.05 and 0.16 mg/mL (TDB, respectively. HPLC-ELSD was shown to be a rapid and effective method for the quantification of lipids within liposome formulations without the need for lipid extraction processes.

  6. Fluorescence quenching of fluorescein by Merocyanine 540 in liposomes

    International Nuclear Information System (INIS)

    Toprak, Mahmut; Meryem Aydin, Burcu; Arik, Mustafa; Onganer, Yavuz

    2011-01-01

    The fluorescence quenching of fluorescein (FL) by merociyanine 540 (MC540) was examined in L-egg lecithin phosphatidycholine (PC) liposomes using spectroscopic methods. The type of quenching mechanism (dynamic or static) was evaluated using the Stern-Volmer plots. Findings were also supported by the temperature studies and florescence decay measurements. The Stern-Volmer equation was utilized to calculate bimolecular quenching constants (K q ). Furthermore, the bimolecular quenching constant of the quencher in the liposomes (K SV ), partition coefficient (K p ), binding constant (K), and corresponding thermodynamic parameters ΔH, ΔS, and ΔG were calculated. The quenching property was also used in determining quantitatively (K p ) the partition coefficient of Merociyanini 540 in PC liposome.The obtained data indicated that static quenching occurred in the system and the K SV values decreased with increasing lipid concentration. In addition, thermodynamic analysis suggested that van der Waals interactions and hydrogen bonding were the main acting forces between fluorescein and merociyanine 540 molecules in the medium. - Highlights: → Fluorescence quenching of FL by MC540 in liposome system was analyzed. → Fluorescence quenching mechanism of FL by MC540 was consistent with the static model. → Binding FL to MC540 was spontaneous and carried out by hydrogen bond and van der Waals forces.

  7. Electrochemical analysis in a liposome suspension using lapachol as a hydrophobic electro active species.

    Science.gov (United States)

    Okumura, Noriko; Wakamatsu, Shiori; Uno, Bunji

    2014-01-01

    This study demonstrated that the electro-chemical analysis of hydrophobic quinones can be performed in liposome suspension systems. We prepared and analyzed liposome suspensions containing lapachol, which is a quinone-based anti-tumor activity compound. In this suspension system, a simple one redox couple of lapachol is observed. These results are quite different from those obtained in organic solvents. In addition, the pH dependence of redox behaviors of lapachol could be observed in multilamellar vesicle (MLV) suspension system. This MLV suspension system method may approximate the electrochemical behavior of hydrophobic compounds in aqueous conditions. A benefit of this liposome suspension system for electrochemical analysis is that it enables to observe water-insoluble compounds without using organic solvents.

  8. Effective in vitro and in vivo gene delivery by the combination of liposomal bubbles (bubble liposomes) and ultrasound exposure.

    Science.gov (United States)

    Suzuki, Ryo; Maruyama, Kazuo

    2010-01-01

    Gene delivery with a physical mechanism using ultrasound (US) and nano/microbubbles is expected as an ideal system in terms of delivering plasmid DNA noninvasively into a specific target site. We developed novel liposomal bubbles (Bubble liposomes (BLs)) containing the lipid nanobubbles of perfluoropropane which were utilized for contrast enhancement in ultrasonography. BLs were smaller in diameter than conventional microbubbles and induced cavitation upon exposure ultrasound. In addition, when coupled with US exposure, BLs could deliver plasmid DNA into various types of cells in vitro and in vivo. The transfection efficiency with BLs and US was higher than that with conventional lipofection method. Therefore, the combination of BLs and US might be an efficient and novel nonviral gene delivery system.

  9. The role of cavitation in liposome formation.

    Science.gov (United States)

    Richardson, Eric S; Pitt, William G; Woodbury, Dixon J

    2007-12-15

    Liposome size is a vital parameter of many quantitative biophysical studies. Sonication, or exposure to ultrasound, is used widely to manufacture artificial liposomes, yet little is known about the mechanism by which liposomes are affected by ultrasound. Cavitation, or the oscillation of small gas bubbles in a pressure-varying field, has been shown to be responsible for many biophysical effects of ultrasound on cells. In this study, we correlate the presence and type of cavitation with a decrease in liposome size. Aqueous lipid suspensions surrounding a hydrophone were exposed to various intensities of ultrasound and hydrostatic pressures before measuring their size distribution with dynamic light scattering. As expected, increasing ultrasound intensity at atmospheric pressure decreased the average liposome diameter. The presence of collapse cavitation was manifested in the acoustic spectrum at high ultrasonic intensities. Increasing hydrostatic pressure was shown to inhibit the presence of collapse cavitation. Collapse cavitation, however, did not correlate with decreases in liposome size, as changes in size still occurred when collapse cavitation was inhibited either by lowering ultrasound intensity or by increasing static pressure. We propose a mechanism whereby stable cavitation, another type of cavitation present in sound fields, causes fluid shearing of liposomes and reduction of liposome size. A mathematical model was developed based on the Rayleigh-Plesset equation of bubble dynamics and principles of acoustic microstreaming to estimate the shear field magnitude around an oscillating bubble. This model predicts the ultrasound intensities and pressures needed to create shear fields sufficient to cause liposome size change, and correlates well with our experimental data.

  10. Thermo-sensitive liposomes loaded with doxorubicin and lysine modified single-walled carbon nanotubes as tumor-targeting drug delivery system.

    Science.gov (United States)

    Zhu, Xiali; Xie, Yingxia; Zhang, Yingjie; Huang, Heqing; Huang, Shengnan; Hou, Lin; Zhang, Huijuan; Li, Zhi; Shi, Jinjin; Zhang, Zhenzhong

    2014-11-01

    This report focuses on the thermo-sensitive liposomes loaded with doxorubicin and lysine-modified single-walled carbon nanotube drug delivery system, which was designed to enhance the anti-tumor effect and reduce the side effects of doxorubicin. Doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes was prepared by reverse-phase evaporation method, the mean particle size was 232.0 ± 5.6 nm, and drug entrapment efficiency was 86.5 ± 3.7%. The drug release test showed that doxorubicin released more quickly at 42℃ than at 37℃. Compared with free doxorubicin, doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes could efficiently cross the cell membranes and afford higher anti-tumor efficacy on the human hepatic carcinoma cell line (SMMC-7721) cells in vitro. For in vivo experiments, the relative tumor volumes of the sarcomaia 180-bearing mice in thermo-sensitive liposomes group and doxorubicin group were significantly smaller than those of N.S. group. Meanwhile, the combination of near-infrared laser irradiation at 808 nm significantly enhanced the tumor growth inhibition both on SMMC-7721 cells and the sarcomaia 180-bearing mice. The quality of life such as body weight, mental state, food and water intake of sarcomaia 180 tumor-bearing mice treated with doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes were much higher than those treated with doxorubicin. In conclusion, doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes combined with near-infrared laser irradiation at 808 nm may potentially provide viable clinical strategies for targeting delivery of anti-cancer drugs. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  11. Liposomal preparation by supercritical fluids technology | Zhong ...

    African Journals Online (AJOL)

    African Journal of Biotechnology ... technology (SCF) has been utilized in liposomal preparation because of its friendliness, nontoxicity to the environment and its possibility to achieve solvent-free liposomes and industrial-scale of liposome production under the conditions of current good manufacturing practice (cGMP).

  12. Liposomal Bupivacaine Injection Technique in Total Knee Arthroplasty.

    Science.gov (United States)

    Meneghini, R Michael; Bagsby, Deren; Ireland, Philip H; Ziemba-Davis, Mary; Lovro, Luke R

    2017-01-01

    Liposomal bupivacaine has gained popularity for pain control after total knee arthroplasty (TKA), yet its true efficacy remains unproven. We compared the efficacy of two different periarticular injection (PAI) techniques for liposomal bupivacaine with a conventional PAI control group. This retrospective cohort study compared consecutive patients undergoing TKA with a manufacturer-recommended, optimized injection technique for liposomal bupivacaine, a traditional injection technique for liposomal bupivacaine, and a conventional PAI of ropivacaine, morphine, and epinephrine. The optimized technique utilized a smaller gauge needle and more injection sites. Self-reported pain scores, rescue opioids, and side effects were compared. There were 41 patients in the liposomal bupivacaine optimized injection group, 60 in the liposomal bupivacaine traditional injection group, and 184 in the conventional PAI control group. PAI liposomal bupivacaine delivered via manufacturer-recommended technique offered no benefit over PAI ropivacaine, morphine, and epinephrine. Mean pain scores and the proportions reporting no or mild pain, time to first opioid, and amount of opioids consumed were not better with PAI liposomal bupivacaine compared with PAI ropivacaine, morphine, and epinephrine. The use of the manufacturer-recommended technique for PAI of liposomal bupivacaine does not offer benefit over a conventional, less expensive PAI during TKA. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  13. Multifunctional quantum dots and liposome complexes in drug delivery.

    Science.gov (United States)

    Wang, Qi; Chao, Yi-Min

    2017-09-03

    Incorporating both diagnostic and therapeutic functions into a single nanoscale system is an effective modern drug delivery strategy. Combining liposomes with semiconductor quantum dots (QDs) has great potential to achieve such dual functions, referred to in this review as a liposomal QD hybrid system (L-QD). Here we review the recent literature dealing with the design and application of L-QD for advances in bio-imaging and drug delivery. After a summary of L-QD synthesis processes and evaluation of their properties, we will focus on their multifunctional applications, ranging from in vitro cell imaging to theranostic drug delivery approaches.

  14. Multifunctional quantum dots and liposome complexes in drug delivery

    Science.gov (United States)

    Wang, Qi; Chao, Yimin

    2018-01-01

    Incorporating both diagnostic and therapeutic functions into a single nanoscale system is an effective modern drug delivery strategy. Combining liposomes with semiconductor quantum dots (QDs) has great potential to achieve such dual functions, referred to in this review as a liposomal QD hybrid system (L-QD). Here we review the recent literature dealing with the design and application of L-QD for advances in bio-imaging and drug delivery. After a summary of L-QD synthesis processes and evaluation of their properties, we will focus on their multifunctional applications, ranging from in vitro cell imaging to theranostic drug delivery approaches. PMID:28866655

  15. Chemical coupling of thiolated chitosan to preformed liposomes improves mucoadhesive properties

    Directory of Open Access Journals (Sweden)

    Gradauer K

    2012-05-01

    about –38 mV to +20 mV, clearly indicating an effective coupling of chitosan-TGA to the surface of liposomes. As a result of mucoadhesion tests, we found an almost two-fold increase in the mucoadhesion of coupled liposomes relative to uncoupled ones. With fluorescence microscopy, we saw a tight adherence of coated particles to the intestinal mucus.Conclusion: Taken together, our current results indicate that thiomer-coated liposomes possess a high potential to be used as an oral drug-delivery system.Keywords: thiomer, liposome, mucoadhesion, chitosan-thioglycolic acid, oral drug delivery

  16. Liposome-based delivery systems for ginsenoside Rh2: in vitro and in vivo comparisons

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Linqiang [China Pharmaceutical University, Department of Pharmaceutics, State Key Laboratory of Natural Medicines (China); Yu, Hua [University of Macao, Institute of Chinese Medical Sciences (China); Yin, Shaoping; Zhang, Ruixia; Zhou, Yudan; Li, Juan, E-mail: lijuancpu@163.com [China Pharmaceutical University, Department of Pharmaceutics, State Key Laboratory of Natural Medicines (China)

    2015-10-15

    The Ginsenoside Rh2 (Rh2) has been shown to possess anti-cancer properties both in vitro and in vivo. However, the poor bioavailability and fast plasma elimination limit the further clinical applications of Rh2 for cancer treatments. In the present study, three types of Rh2-loaded liposomes including Rh2-loaded normal liposome (Rh2-LP), Rh2-loaded cationic liposome (Rh2-CLP), and Rh2-loaded Methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA) liposome (Rh2-PLP) have been optimized and prepared with mean particle size of 80–125 nm. Compared to Rh2-LP, surface modifications with mPEG or octadecylamine significantly improve the physicochemical and biological properties both in vitro and in vivo. Moreover, PLP presented better tumor accumulation of the fluorescent cyanine dye, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide (DiR) in HepG2-xenografted nude mice than CLP (1.3-fold) or LP (1.6-fold) and prolong the resident time of DiR in tumor and organs (more than 24 h). The in vivo anti-cancer efficacy assessments indicate that Rh2-PLP presents the most activity on suppressing tumor growth in HepG2-xenografted mice than Rh2-LP and Rh2-CLP and without any significant toxicity. Our results indicate that mPEG-PLA modified liposome should be a potential and promising strategy to enhance the therapeutic index for anti-cancer agents.

  17. Performance of Uplink Carrier Aggregation in LTE-Advanced Systems

    DEFF Research Database (Denmark)

    Wang, Hua; Rosa, Claudio; Pedersen, Klaus

    2010-01-01

    Carrier aggregation (CA) has been proposed to aggregate two or more component carriers (CCs) to support a much wider transmission bandwidth for LTE-Advanced systems. With carrier aggregation, it is possible to schedule a user equipment (UE) on multiple component carriers simultaneously. In this p...

  18. Liposomes coated with hydrophobically modified hydroxyethyl cellulose: Influence of hydrophobic chain length and degree of modification.

    Science.gov (United States)

    Smistad, Gro; Nyström, Bo; Zhu, Kaizheng; Grønvold, Marthe Karoline; Røv-Johnsen, Anne; Hiorth, Marianne

    2017-08-01

    Nanoparticulate systems with an uncharged hydrophilic surface may have a great potential in mucosal drug delivery. In the present study liposomes were coated with hydrophobically modified hydroxyethyl cellulose (HM-HEC) to create a sterically stabilized liposomal system with an uncharged surface. The aim was to clarify the influence of the amount of hydrophobic modification of HEC and the length of the hydrophobic moiety, on the stability of the system and on the release properties. HM-HEC with different degrees of hydrophobic modification (1 and 2mol%) and hydrophobic groups with different chain lengths (C8, C12, C16) were included in the study, as well as fluid phase and gel phase liposomes. Both types of liposomes were successfully coated with HM-HEC containing 1mol% of hydrophobic groups, while 2mol% did not work for the intended pharmaceutical applications. The polymer coated gel phase liposomes were stable (size, zeta potential, leakage) for 24 weeks at 4°C, with no differences between the C8 and C16 HM-HEC coating. For the fluid phase liposomes a size increase was observed after 24 weeks at 4°C for all formulations; the C8 HM-HEC coated liposomes increased the most. No differences in the leakage during storage at 4°C or in the release at 35°C were observed between the fluid phase formulations. To conclude; HM-HEC with a shorter hydrophobic chain length resulted in a less stable product for the fluid phase liposomes, while no influence of the chain length was observed for the gel phase liposomes (1mol% HM). Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Fiber-optic triggered release of liposome in vivo: implication of personalized chemotherapy.

    Science.gov (United States)

    Huang, Huei-Ling; Lu, Pei-Hsuan; Yang, Hung-Chih; Lee, Gi-Da; Li, Han-Ru; Liao, Kuo-Chih

    2015-01-01

    The aim of this research is to provide proof of principle by applying the fiber-optic triggered release of photo-thermally responsive liposomes embedded with gold nanoparticles (AuNPs) using a 200 μm fiber with 65 mW and 532 nm excitation for topical release in vivo. The tunable delivery function can be paired with an apoptosis biosensor based on the same fiber-optic configuration for providing real-time evaluation of chemotherapy efficacy in vivo to perform as a personalized chemotherapy system. The pattern of topical release triggered by laser excitation conveyed through optical fibers was monitored by the increase in fluorescence resulting from the dilution of self-quenching (75 mM) fluorescein encapsulated in liposomes. In in vitro studies (in 37°C phosphate buffer saline), the AuNP-embedded liposomes showed a more efficient triggered release (74.53%±1.63% in 40 minutes) than traditional temperature-responsive liposomes without AuNPs (14.53%±3.17%) or AuNP-liposomes without excitation (21.92%±2.08%) by spectroscopic measurements. Using the mouse xenograft studies, we first demonstrated that the encapsulation of fluorescein in liposomes resulted in a more substantial content retention (81%) in the tumor than for free fluorophores (14%) at 120 minutes after administration from in vivo fluorescence imaging. Furthermore, the preliminary results also suggested the tunable release capability of the system by demonstrating consecutive triggered releases with fiber-optic guided laser excitation.

  20. Polymer coated liposomes for dental drug delivery--interactions with parotid saliva and dental enamel.

    Science.gov (United States)

    Nguyen, S; Hiorth, M; Rykke, M; Smistad, G

    2013-09-27

    The interactions between pectin coated liposomes and parotid saliva and dental enamel were studied to investigate their potential to mimic the protective biofilm formed naturally on tooth surfaces. Different pectin coated liposomes with respect to pectin type (LM-, HM- and AM-pectin) and concentration (0.05% and 0.2%) were prepared. Interactions between the pectin coated liposomes and parotid saliva were studied by turbidimetry and imaging by atomic force microscopy. The liposomes were adsorbed to hydroxyapatite (HA) and human dental enamel using phosphate buffer and parotid saliva as adsorption media. A continuous flow was imposed on the enamel surfaces for various time intervals to examine their retention on the dental enamel. The results were compared to uncoated, charged liposomes. No aggregation tendencies for the pectin coated liposomes and parotid saliva were revealed. This makes them promising as drug delivery systems to be used in the oral cavity. In phosphate buffer the adsorption to HA of pectin coated liposomes was significantly lower than the negative liposomes. The difference diminished in parotid saliva. Positive liposomes adsorbed better to the dental enamel than the pectin coated liposomes. However, when subjected to flow for 1h, no significant differences in the retention levels on the enamel were found between the formulations. For all formulations, more than 40% of the liposomes still remained on the enamel surfaces. At time point 20 min the retention of HM-pectin coated and positive liposomes were significantly higher. It was concluded that pectin coated liposomes can adsorb to HA as well as to the dental enamel. Their ability to retain on the enamel surfaces promotes the concept of using them as protective structures for the teeth. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Assembly of Liposomes Controlled by Triple Helix Formation

    DEFF Research Database (Denmark)

    Vogel, Stefan; Jakobsen, Ulla

    2013-01-01

    Attachment of DNA to the surface of different solid nanoparticles (e.g. gold- and silica nanoparticles) is well established and a number of DNA-modified solid nanoparticle systems have been applied to thermal denaturation analysis of oligonucleotides. We report herein the non-covalent immobilizat...... analysis (NTA) and dynamic light scattering (DLS) show independently from ultraviolet spectroscopy experiments the formation of liposome aggregates.......-covalent immobilization of oligonucleotides on the surface of soft nanoparticles (e.g. liposomes) and the subsequent controlled assembly by DNA triple helix formation. The non-covalent approach avoids tedious surface chemistry and necessary purification procedures and can simplify and extend the available methodology...... sequences (G or C-rich) to explore the applicability of the method for different triple helical assembly modes. We demonstrate advantages and limitations of the approach and proof the reversible and reproducible formation of liposome aggregates during thermal denaturation cycles. Nanoparticle tracking...

  2. Binding of Diphtheria Toxin to Phospholipids in Liposomes

    Science.gov (United States)

    Alving, Carl R.; Iglewski, Barbara H.; Urban, Katharine A.; Moss, Joel; Richards, Roberta L.; Sadoff, Jerald C.

    1980-04-01

    Diphtheria toxin bound to the phosphate portion of some, but not all, phospholipids in liposomes. Liposomes consisting of dimyristoyl phosphatidylcholine and cholesterol did not bind toxin. Addition of 20 mol% (compared to dimyristoyl phosphatidylcholine) of dipalmitoyl phosphatidic acid, dicetyl phosphate, phosphatidylinositol phosphate, cardiolipin, or phosphatidylserine in the liposomes resulted in substantial binding of toxin. Inclusion of phosphatidylinositol in dimyristol phosphatidylcholine / cholesterol liposomes did not result in toxin binding. The calcium salt of dipalmitoyl phosphatidic acid was more effective than the sodium salt, and the highest level of binding occurred with liposomes consisting only of dipalmitoyl phosphatidic acid (calcium salt) and cholesterol. Binding of toxin to liposomes was dependent on pH, and the pattern of pH dependence varied with liposomes having different compositions. Incubation of diphtheria toxin with liposomes containing dicetyl phosphate resulted in maximal binding at pH 3.6, whereas binding to liposomes containing phosphatidylinositol phosphate was maximal above pH 7. Toxin did not bind to liposomes containing 20 mol% of a free fatty acid (palmitic acid) or a sulfated lipid (3-sulfogalactosylceramide). Toxin binding to dicetyl phosphate or phosphatidylinositol phosphate was inhibited by UTP, ATP, phosphocholine, or p-nitrophenyl phosphate, but not by uracil. We conclude that (a) diphtheria toxin binds specifically to the phosphate portion of certain phospholipids, (b) binding to phospholipids in liposomes is dependent on pH, but is not due only to electrostatic interaction, and (c) binding may be strongly influenced by the composition of adjacent phospholipids that do not bind toxin. We propose that a minor membrane phospholipid (such as phosphatidylinositol phosphate or phosphatidic acid), or that some other phosphorylated membrane molecule (such as a phosphoprotein) may be important in the initial binding of

  3. Ultraviolet- and sunlight-induced lipid peroxidation in liposomal membrane

    International Nuclear Information System (INIS)

    Mandal, T.K.; Chatterjee, S.N.

    1980-01-01

    Ultraviolet radiation and sunlight caused lipid peroxidation in the liposomal membrane (as detected by measurement of the oxidation index, A 233 /A 215 , and the amount of malondialdehyde formed) and made the membrane leaky (as revealed by the release of the trapped chromate anions). The oxidation index and the formation of malondialdehyde increased linearly with increasing dose of radiation and depended significantly on the dose rate. The effects were smaller in liposomes derived from Vibrio cholerae phospholipid than in those derived from egg lecithin. The effects of the radiation dose and dose rate on hemolysis and peroxidation (MDA formation) of the erythrocyte membrane followed a similar pattern. A direct correlation between the percentage leakage of chromate (Y) and the oxidation index (X) of the liposomal system was obtained as Y = 236.5 x X

  4. Liposomes equipped with cell penetrating peptide BR2 enhances chemotherapeutic effects of cantharidin against hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Xue; Lin, Congcong; Lu, Aiping; Lin, Ge; Chen, Huoji; Liu, Qiang; Yang, Zhijun; Zhang, Hongqi

    2017-11-01

    A main hurdle for the success of tumor-specific liposomes is their inability to penetrate tumors efficiently. In this study, we incorporated a cell-penetrating peptide BR2 onto the surface of a liposome loaded with the anticancer drug cantharidin (CTD) to create a system targeting hepatocellular carcinoma (HCC) cells more efficiently and effectively. The in vitro cytotoxicity assay comparing the loaded liposomes' effects on hepatocellular cancer HepG2 and the control Miha cells showed that CTD-loaded liposomes had a stronger anticancer effect after BR2 modification. The cellular uptake results of HepG2 and Miha cells further confirmed the superior ability of BR2-modified liposomes to penetrate cancer cells. The colocalization study revealed that BR2-modified liposomes could enter tumor cells and subsequently release drugs. A higher efficiency of delivery by BR2 liposomes as compared to unmodified liposomes was evident by evaluation of the HepG2 tumor spheroids penetration and inhibition. The biodistribution studies and anticancer efficacy results in vivo showed the significant accumulation of BR2-modified liposomes into tumor sites and an enhanced tumor inhibition. In conclusion, BR2-modified liposomes improve the anticancer potency of drugs for HCC.

  5. Mechanical Division of Cell-Sized Liposomes

    NARCIS (Netherlands)

    Deshpande, S.R.; Kerssemakers, J.W.J.; Dekker, C.

    2018-01-01

    Liposomes, self-assembled vesicles with a lipid-bilayer boundary similar to cell membranes, are extensively used in both fundamental and applied sciences. Manipulation of their physical properties, such as growth and division, may significantly expand their use as model systems in cellular and

  6. Deciphering the Functional Composition of Fusogenic Liposomes

    Science.gov (United States)

    Kolašinac, Rejhana; Kleusch, Christian; Braun, Tobias; Merkel, Rudolf; Csiszár, Agnes

    2018-01-01

    Cationic liposomes are frequently used as carrier particles for nucleic acid delivery. The most popular formulation is the equimolar mixture of two components, a cationic lipid and a neutral phosphoethanolamine. Its uptake pathway has been described as endocytosis. The presence of an aromatic molecule as a third component strongly influences the cellular uptake process and results in complete membrane fusion instead of endocytosis. Here, we systematically varied all three components of this lipid mixture and determined how efficiently the resulting particles fused with the plasma membrane of living mammalian cells. Our results show that an aromatic molecule and a cationic lipid component with conical molecular shape are essential for efficient fusion induction. While a neutral lipid is not mandatory, it can be used to control fusion efficiency and, in the most extreme case, to revert the uptake mechanism back to endocytosis. PMID:29364187

  7. Amperometric Adhesion Signals of Liposomes, Cells and Droplets

    OpenAIRE

    Ivošević DeNardis, N.; Žutić, V.; Svetličić, V.; Frkanec, R.

    2009-01-01

    Individual soft microparticles (liposomes, living cells and organic droplets) in aqueous media are characterized by their adhesion signals using amperometry at the dropping mercury electrode. We confirmed that the general mechanism established for adhesion of hydrocarbon droplets and cells is valid as well for liposome adhesion within a wide range of surface charge densities. Incidents and shape of adhesion signals in liposome suspensions reflect liposome polydispersity, surface charge den...

  8. "Nail" and "comb" effects of cholesterol modified NIPAm oligomers on cancer targeting liposomes

    KAUST Repository

    Li, Wengang; Deng, Lin; Moosa, Basem; Wang, Guangchao; Mashat, Afnan; Khashab, Niveen M.

    2014-01-01

    Thermosensitive liposomes are a promising approach to controlled release and reduced drug cytotoxicity. Low molecular weight N-isopropylacrylamide (NIPAm) oligomers (NOs) with different architectures (main chain NOs (MCNOs) and side chain NOs (SCNOs)) were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization and radical polymerization and then separately used to prepare thermosensitive liposomes. A more controlled and enhanced release was observed for both NO liposomes compared to pristine ones. Two release mechanisms depending on the oligomer architecture, namely "nail" for MCNOs and "comb" for SCNOs, are proposed. In addition to thermosensitivity, the cancer targeting property of NO liposomes was achieved by further biotinylation of the delivery system. © The Royal Society of Chemistry.

  9. Design and syntheses of mono and multivalent mannosyl-lipoconjugates for targeted liposomal drug delivery.

    Science.gov (United States)

    Štimac, Adela; Cvitaš, Jelena TrmĿiĿ; Frkanec, Leo; Vugrek, Oliver; Frkanec, Ruža

    2016-09-10

    Multivalent mannosyl-lipoconjugates may be of interest for glycosylation of liposomes and targeted drug delivery because the mannose specifically binds to C-type lectin receptors on the particular cells. In this paper syntheses of two types of novel O-mannosides are presented. Conjugates 1 and 2 with a COOH- and NH2-functionalized spacer and the connection to a lysine and FmocNH-PEG-COOH, are described. The coupling reactions of prepared intermediates 6 and 4 with a PEGylated-DSPE or palmitic acid, respectively, are presented. Compounds 5, mono-, 8, di- and 12, tetravalent mannosyl-lipoconjugates, were synthesized. The synthesized compounds were incorporated into liposomes and liposomal preparations featuring exposed mannose units were characterized. Carbohydrate liposomal quartz crystal microbalance based assay has been established for studying carbohydrate-lectin binding. It was demonstrated that liposomes with incorporated mannosyl-lipoconjugates were effectively recognized by Con A and have great potential to be used for targeted liposomal drug delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Novel local drug delivery system using thermoreversible gel in combination with polymeric microspheres or liposomes.

    Science.gov (United States)

    Arai, Takao; Benny, Ofra; Joki, Tatsuhiro; Menon, Lata G; Machluf, Marcelle; Abe, Toshiaki; Carroll, Rona S; Black, Peter M

    2010-04-01

    The purpose of our study was to evaluate the application of thermoreversible gelation polymer (TGP) as a local drug delivery system for malignant glioma. Polymeric microspheres or liposomes loaded with doxorubicin (sphere-dox or lipo-dox) were combined with TGP to provide continuous drug delivery of doxorubicin (dox) for kinetic release studies and cell viability assays on glioma cell lines in vitro. For in vivo studies, TGP loaded with dox alone (TGP-dox) was combined with sphere-dox or lipo-dox. Their antitumor effects on subcutaneous human glioma xenografts were evaluated in nude mice. In vitro, TGP combined with sphere-dox or lipo-dox released dox for up to 30 days. In vivo, TGP-dox combined with sphere-dox or lipo-dox inhibited subcutaneous glioma tumor growth until day 32 and day 38, respectively. TGP in combination with microspheres or liposomes successfully prolonged the release of dox and its antitumor effects.

  11. Calcipotriol delivery into the skin with PEGylated liposomes

    DEFF Research Database (Denmark)

    Knudsen, Nina Østergaard; Rønholt, Stine; Salte, Ragnhild Djønne

    2012-01-01

    The d-vitamin analogue calcipotriol is commonly used for topical treatment of psoriasis, but skin penetration is required for calcipotriol to reach its pharmacological target: the keratinocytes in the lower epidermis. Liposomes can enhance the delivery of drugs into the skin, but a major challenge...... of the liposomes and the ability to deliver membrane-intercalated calcipotriol into the skin. Inclusion of 0.5, l and 5mol% PEG-DSPE in the membrane enhanced the colloidal stability of the liposomes without compromising the delivery of calcipotriol from the vehicle into excised pig skin. Calcipotriol...... to large multilamellar vesicles, indicating that the liposomes to some extent migrate as intact vesicles into the stratum corneum. However, calcipotriol penetrated the skin better than the lipid component of the liposomes, suggesting that at least a fraction of the drug is released from the liposomes...

  12. Fiber-optic triggered release of liposome in vivo: implication of personalized chemotherapy

    Directory of Open Access Journals (Sweden)

    Huang HL

    2015-08-01

    Full Text Available Huei-Ling Huang,1 Pei-Hsuan Lu,1 Hung-Chih Yang,1 Gi-Da Lee,1,2 Han-Ru Li,1 Kuo-Chih Liao1 1Graduate Institute of Biomedical Engineering, National Chung Hsing University, 2Department of Radiology, Taichung Veterans General Hospital, Taichung, Taiwan Abstract: The aim of this research is to provide proof of principle by applying the fiber-optic triggered release of photo-thermally responsive liposomes embedded with gold nanoparticles (AuNPs using a 200 µm fiber with 65 mW and 532 nm excitation for topical release in vivo. The tunable delivery function can be paired with an apoptosis biosensor based on the same fiber-optic configuration for providing real-time evaluation of chemotherapy efficacy in vivo to perform as a personalized chemotherapy system. The pattern of topical release triggered by laser excitation conveyed through optical fibers was monitored by the increase in fluorescence resulting from the dilution of self-quenching (75 mM fluorescein encapsulated in liposomes. In in vitro studies (in 37°C phosphate buffer saline, the AuNP-embedded liposomes showed a more efficient triggered release (74.53%±1.63% in 40 minutes than traditional temperature-responsive liposomes without AuNPs (14.53%±3.17% or AuNP-liposomes without excitation (21.92%±2.08% by spectroscopic measurements. Using the mouse xenograft studies, we first demonstrated that the encapsulation of fluorescein in liposomes resulted in a more substantial content retention (81% in the tumor than for free fluorophores (14% at 120 minutes after administration from in vivo fluorescence imaging. Furthermore, the preliminary results also suggested the tunable release capability of the system by demonstrating consecutive triggered releases with fiber-optic guided laser excitation. Keywords: fiber-optic guided excitation, light excitation triggered release, photo-thermal responsive liposome, gold nanoparticles, tunable release in vivo

  13. Process optimization by use of design of experiments: Application for liposomalization of FK506.

    Science.gov (United States)

    Toyota, Hiroyasu; Asai, Tomohiro; Oku, Naoto

    2017-05-01

    Design of experiments (DoE) can accelerate the optimization of drug formulations, especially complexed formulas such as those of drugs, using delivery systems. Administration of FK506 encapsulated in liposomes (FK506 liposomes) is an effective approach to treat acute stroke in animal studies. To provide FK506 liposomes as a brain protective agent, it is necessary to manufacture these liposomes with good reproducibility. The objective of this study was to confirm the usefulness of DoE for the process-optimization study of FK506 liposomes. The Box-Behnken design was used to evaluate the effect of the process parameters on the properties of FK506 liposomes. The results of multiple regression analysis showed that there was interaction between the hydration temperature and the freeze-thaw cycle on both the particle size and encapsulation efficiency. An increase in the PBS hydration volume resulted in an increase in encapsulation efficiency. Process parameters had no effect on the ζ-potential. The multiple regression equation showed good predictability of the particle size and the encapsulation efficiency. These results indicated that manufacturing conditions must be taken into consideration to prepare liposomes with desirable properties. DoE would thus be promising approach to optimize the conditions for the manufacturing of liposomes. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Targeting doxorubicin encapsulated in stealth liposomes to solid tumors by non thermal diode laser.

    Science.gov (United States)

    Ghannam, Magdy M; El Gebaly, Reem; Fadel, Maha

    2016-04-05

    The use of liposomes as drug delivery systems is the most promising technique for targeting drug especially for anticancer therapy. In this study sterically stabilized liposomes was prepared from DPPC/Cholesterol/PEG-PE encapsulated doxorubicin. The effect of lyophilization on liposomal stability and hence expiration date were studied. Moreover, the effect of diode laser on the drug released from liposomesin vitro and in vivo in mice carrying implanted solid tumor were also studied. The results indicated that lyophilization of the prepared liposomes encapsulating doxorubicin led to marked stability when stored at 5 °C and it is possible to use the re-hydrated lyophilized liposomes within 12 days post reconstitution. Moreover, the use of low energy diode laser for targeting anticancer drug to the tumor cells is a promising method in cancer therapy. We can conclude that lyophilization of the liposomes encapsulating doxorubicin lead to marked stability for the liposomes when stored at 5 °C. Moreover, the use of low energy diode laser for targeting anticancer drug to the tumor cells through the use of photosensitive sterically stabilized liposomes loaded with doxorubicin is a promising method. It proved to be applicable and successful for treatment of Ehrlich solid tumors implanted in mice and eliminated toxic side effects of doxorubicin.

  15. Sustained release of intravitreal flurbiprofen from a novel drug-in-liposome-in-hydrogel formulation.

    Science.gov (United States)

    Pachis, K; Blazaki, S; Tzatzarakis, M; Klepetsanis, P; Naoumidi, E; Tsilimbaris, M; Antimisiaris, S G

    2017-11-15

    A novel Flurbiprofen (FLB)-in-liposome-in-hydrogel formulation was developed, as a method to sustain the release and increase the ocular bioavailability of FLB following intravitreal injection. For this, FLB loading into liposomes was optimized and liposomes were entrapped in thermosensitive hydrogels consisted of Pluronic F-127 (P). FLB solution, liposomes, and FLB dissolved in hydrogel were also used as control formulations. Actively loaded liposomes were found to be optimal for high FLB loading and small size, while in vitro studies revealed that P concentration of 18% (w/v) was best to retain the integrity of the hydrogel-dispersed liposome, compared to a 20% concentration. The in vitro release of FLB was significantly sustained when FLB-liposomes were dispersed in the hydrogel compared to hydrogel dissolved FLB, as well as the other control formulations. In vivo studies were carried out in pigmented rabbits which were injected through a 27G needle with 1mg/mL FLB in the different formulation-types. Ophthalmic examinations after intravitreal injection of all FLB formulations, revealed no evidence of inflammation, hemorrhage, uveitis or endophthalmitis. Pharmacokinetic analysis results confirm that the hybrid drug delivery system increases the bioavailability (by 1.9 times compared to solution), and extends the presence of the drug in the vitreous cavity, while liposome and hydrogel formulations demonstrate intermediate performance. Furthermore the hybrid system increases MRT of FLB in aqueous humor and retina/choroid tissues, compared to all the control formulations. Currently the potential therapeutic advances of FLB sustained release formulations for IVT administration are being evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Liposome Technology for Industrial Purposes

    Directory of Open Access Journals (Sweden)

    Andreas Wagner

    2011-01-01

    Full Text Available Liposomes, spherical vesicles consisting of one or more phospholipid bilayers, were first described in the mid 60s by Bangham and coworkers. Since then, liposomes have made their way to the market. Today, numerous lab scale but only a few large-scale techniques are available. However, a lot of these methods have serious limitations in terms of entrapment of sensitive molecules due to their exposure to mechanical and/or chemical stress. This paper summarizes exclusively scalable techniques and focuses on strengths, respectively, limitations in respect to industrial applicability. An additional point of view was taken to regulatory requirements concerning liposomal drug formulations based on FDA and EMEA documents.

  17. Development of a glucose-sensitive drug delivery device: Microencapsulated liposomes and poly(2-ethylacrylic acid)

    Science.gov (United States)

    Kanokpanont, Sorada

    The current study is the development a self-regulated, glucose responsive drug delivery system, using dioleoylphosphatidylcholine (DOPC) liposomes, a pH sensitive polymer, poly (2-ethylacrylic acid)(PEAA), and the feed back reaction of glucose with glucose oxidase enzyme (GO). The thesis investigates the use of PEAR and liposomes to work inside a microcapsule in response to the glucose level of the environment, by following the release of fluorescence probes, 8-aminonapthalene-1,3,6-trisulfonic acid, disodium salt/p-xylene-bis-pyridimuim bromide (ANTS/DPX) and a model protein, myoglobin. The continuing studies of PEAR and liposome interaction indicated an evidence of the previous hypothesis of two-mode release at different pHs. Differential scanning calorimetric studies of DOPC and PEAA complexes revealed the possibility of polymer adsorption to the liposomes in the pH range 5.5--7.0 and insertion in the liposome bilayer at pH pH, PEAR concentration, presence of cholesterol in the liposomes, Ca 2+, and the concentration of sodium alginate. We have also shown possibilities of anchoring PEAR on to liposome by covalent conjugation although this led to inactivation of the polymer. It is also possible to entrap small molecular weight PEAA in liposomes. The evidence of the pH-induced protein release by the interaction of PEAA and liposomes was first demonstrated in this thesis. Kinetic parameters of GO were estimated to use as a basis for determination optimal concentration in the capsules. The pH reduction inside the capsule due to GO reaction showed positive results for the use of GO in a non-buffered system. The procedure of liquid-core alginate capsules was modified to facilitate the pH-responsive release of ANTS/DPX and myoglobin. The capsules responded to high blood glucose concentration by releasing myoglobin within 30 minutes. Although more studies are required to improve the response of the system to the normal blood glucose and to control the total protein

  18. Liposome encapsulation of fluorescent nanoparticles: Quantum dots and silica nanoparticles

    International Nuclear Information System (INIS)

    Chen, C.-S.; Yao Jie; Durst, Richard A.

    2006-01-01

    Quantum dots (QDs) and silica nanoparticles (SNs) are relatively new classes of fluorescent probes that overcome the limitations encountered by organic fluorophores in bioassay and biological imaging applications. We encapsulated QDs and SNs in liposomes and separated nanoparticle-loaded liposomes from unencapsulated nanoparticles by size exclusion chromatography. Fluorescence correlation spectroscopy was used to measure the average number of nanoparticles inside each liposome. Results indicated that nanoparticle-loaded liposomes were formed and separated from unencapsulated nanoparticles by using a Sepharose gel. As expected, fluorescence self-quenching of nanoparticles inside liposomes was not observed. Each liposome encapsulated an average of three QDs. These studies demonstrated that nanoparticles could be successfully encapsulated into liposomes and provided a methodology to quantify the number of nanoparticles inside each liposome by fluorescence correlation spectroscopy

  19. Thermo-responsive magnetic liposomes for hyperthermia-triggered local drug delivery.

    Science.gov (United States)

    Dai, Min; Wu, Cong; Fang, Hong-Ming; Li, Li; Yan, Jia-Bao; Zeng, Dan-Lin; Zou, Tao

    2017-06-01

    We prepared and characterised thermo-responsive magnetic liposomes, which were designed to combine features of magnetic targeting and thermo-responsive control release for hyperthermia-triggered local drug delivery. The particle size and zeta-potential of the thermo-responsive magnetic ammonium bicarbonate (MagABC) liposomes were about 210 nm and -14 mV, respectively. The MagABC liposomes showed encapsulation efficiencies of about 15% and 82% for magnetic nanoparticles (mean crystallite size 12 nm) and doxorubicin (DOX), respectively. The morphology of the MagABC liposomes was visualised using transmission electron microscope (TEM). The MagABC liposomes showed desired thermo-responsive release. The MagABC liposomes, when physically targeted to tumour cells in culture by a permanent magnetic field yielded a substantial increase in intracellular accumulation of DOX as compared to non-magnetic ammonium bicarbonate (ABC) liposomes. This resulted in a parallel increase in cytotoxicity for DOX loaded MagABC liposomes over DOX loaded ABC liposomes in tumour cells.

  20. Near-infrared light-responsive liposomal contrast agent for photoacoustic imaging and drug release applications.

    Science.gov (United States)

    Sivasubramanian, Kathyayini; Mathiyazhakan, Malathi; Wiraja, Christian; Upputuri, Paul Kumar; Xu, Chenjie; Pramanik, Manojit

    2017-04-01

    Photoacoustic imaging has become an emerging tool for theranostic applications. Not only does it help in release and therapeutic applications. We explore near-infrared light-sensitive liposomes coated with gold nanostars (AuNSs) for both imaging and drug release applications using a photoacoustic imaging system. Being amphiphilic, the liposomes lipid bilayer and the aqueous core enable encapsulation of both hydrophobic and hydrophilic drugs. The AuNSs on the surface of the liposomes act as photon absorbers due to their intrinsic surface plasmon resonance. Upon excitation by laser light at specific wavelength, AuNSs facilitate rapid release of the contents encapsulated in the liposomes due to local heating and pressure wave formation (photoacoustic wave). Herein, we describe the design and optimization of the AuNSs-coated liposomes and demonstrate the release of both hydrophobic and hydrophilic model drugs (paclitaxel and calcein, respectively) through laser excitation at near-infrared wavelength. The use of AuNSs-coated liposomes as contrast agents for photoacoustic imaging is also explored with tissue phantom experiments. In comparison to blood, the AuNSs-coated liposomes have better contrast (approximately two times) at 2-cm imaging depth.

  1. A novel application of maleimide for advanced drug delivery: in vitro and in vivo evaluation of maleimide-modified pH-sensitive liposomes

    Directory of Open Access Journals (Sweden)

    Li T

    2013-10-01

    Full Text Available Tianshu Li, Shinji TakeokaDepartment of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University (TWIns, Shinjuku-ku, Tokyo, JapanAbstract: Maleimide is a stable and easy-to-handle moiety that rapidly and covalently conjugates thiol groups of cysteine residues in proteins or peptides. Herein, we use maleimide to modify the surface of liposomes in order to obtain an advanced drug delivery system. Employing a small amount (0.3 mol% of maleimide-polyethylene glycol (PEG to modify the surface of the liposomes M-GGLG-liposomes, composed of 1,5-dihexadecyl N,N-diglutamyl-lysyl-L-glutamate (GGLG/cholesterol/poly(ethylene glycol 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (PEG5000-DSPE/maleimide-PEG5000-Glu2C18 at a molar ratio of 5:5:0.03:0.03, drug delivery efficiency was remarkably improved both in vitro and in vivo compared to unmodified liposomes (GGLG-liposomes, composed of GGLG/cholesterol/PEG5000-DSPE/PEG5000-Glu2C18 at a molar ratio of 5:5:0.03:0.03. Moreover, this modification did not elicit any detectable increase in cytotoxicity. The maleimide-modification did not alter the physical characteristics of the liposomes such as size, zeta potential, pH sensitivity, dispersibility and drug encapsulation efficiency. However, M-GGLG-liposomes were more rapidly (≥2-fold internalized into HeLa, HCC1954, and MDA-MB-468 cells compared to GGLG-liposomes. In vivo, M-GGLG-liposomes encapsulating doxorubicin (M-GGLG-DOX-liposomes also showed a more potent antitumor effect than GGLG-DOX-liposomes and the widely used 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC-DOX-liposomes after two subcutaneous injections around breast cancer tissue in mice. The biodistribution of liposomes in this model was observed using an in vivo imaging system, which showed that M-GGLG-liposomes were present for significantly longer at the injection site compared to GGLG-liposomes. The outstanding biological functions of

  2. Rapid delivery of small interfering RNA by biosurfactant MEL-A-containing liposomes

    International Nuclear Information System (INIS)

    Inoh, Yoshikazu; Furuno, Tadahide; Hirashima, Naohide; Kitamoto, Dai; Nakanishi, Mamoru

    2011-01-01

    Highlights: ► We use MEL-A-containing cationic liposomes for siRNA delivery. ► MEL-A-containing cationic liposomes can efficiently and rapidly deliver siRNA into the cytoplasm. ► Rapid delivery of siRNA is due to the membrane fusion between liposomes and plasma membrane. -- Abstract: The downregulation of gene expression by RNA interference holds great potential for genetic analysis and gene therapy. However, a more efficient delivery system for small interfering RNA (siRNA) into the target cells is required for wide fields such as cell biology, physiology, and clinical application. Non-viral vectors are stronger candidates than viral vectors because they are safer and easier to prepare. We have previously used a new method for gene transfection by combining cationic liposomes with the biosurfactant mannosylerythritol lipid-A (MEL-A). The novel MEL-A-containing cationic liposomes rapidly delivered DNA (plasmids and oligonucleotides) into the cytosol and nucleus through membrane fusion between liposomes and the plasma membrane, and consequently, enhanced the gene transfection efficiency. In this study, we determined the efficiency of MEL-A-containing cationic liposomes for siRNA delivery. We observed that exogenous and endogenous protein expression was suppressed by approximately 60% at 24 h after brief (30 min) incubation of target cells with MEL-A-containing cationic liposome/siRNA complexes. Confocal microscopic analysis showed that suppression of protein expression was caused by rapid siRNA delivery into the cytosol. We found that the MEL-A-containing cationic liposomes directly delivered siRNA into the cytoplasm by the membrane fusion in addition to endocytotic pathway whereas Lipofectamine™ RNAiMax delivered siRNA only by the endocytotic pathway. It seems that the ability to rapidly and directly deliver siRNA into the cytosol using MEL-A-containing cationic liposomes is able to reduce immune responses, cytotoxicity, and other side effects caused by

  3. Liposomes containing alkylated methotrexate analogues for phospholipase A(2) mediated tumor targeted drug delivery

    DEFF Research Database (Denmark)

    Kaasgaard, Thomas; Andresen, Thomas Lars; Jensen, Simon Skøde

    2009-01-01

    of alkylated compounds in liposomes, it was demonstrated that the MTX-analogue partitioned into the water phase and thereby became available for cell uptake. It was concluded that liposomes containing alkylated MTX-analogues show promise as a drug delivery system, although the MTX-analogue needs to be more......Two lipophilic methotrexate analogues have been synthesized and evaluated for cytotoxicity against KATO III and HT-29 human colon cancer cells. Both analogues contained a C-16-alkyl chain attached to the gamma-carboxylic acid and one of the analogues had an additional benzyl group attached...... cytotoxicity was incorporated into liposomes that were designed to be particularly Susceptible to a liposome degrading enzyme, secretory phospholipase A(2) (sPLA(2)), which is found in high concentrations in tumors of several different cancer types. Liposome incorporation was investigated by differential...

  4. Imaging phospholipid conformational disorder and packing in giant multilamellar liposome by confocal Raman microspectroscopy

    Science.gov (United States)

    Noothalapati, Hemanth; Iwasaki, Keita; Yoshimoto, Chikako; Yoshikiyo, Keisuke; Nishikawa, Tomoe; Ando, Masahiro; Hamaguchi, Hiro-o.; Yamamoto, Tatsuyuki

    2017-12-01

    Liposomes are closed phospholipid bilayer systems that have profound applications in fundamental cell biology, pharmaceutics and medicine. Depending on the composition (pure or mixture of phospholipids, presence of cholesterol) and preparation protocol, intra- and inter-chain molecular interactions vary leading to changes in the quality (order and packing) of liposomes. So far it is not possible to image conformational disorders and packing densities within a liposome in a straightforward manner. In this study, we utilized confocal Raman microspectroscopy to visualize structural disorders and packing efficiency within a giant multilamellar liposome model by focusing mainly on three regions in the vibrational spectrum (Csbnd C stretching, Csbnd H deformation and Csbnd H stretching). We estimated properties such as trans/gauche isomers and lateral packing probability. Interestingly, our Raman imaging studies revealed gel phase rich domains and heterogeneous lateral packing within the giant multilamellar liposome.

  5. Reversal of the multidrug resistance by drug combination using multifunctional liposomes

    Science.gov (United States)

    Patel, Niravkumar R.

    One of the major obstacles to the success of cancer chemotherapy is the multi-drug resistance (MDR) that results due mainly to the over-expression of drug efflux transporter pumps such as P-glycoprotein (P-gp). Highly efficacious third generation P-gp inhibitors, like tariquidar, have shown promising results against MDR. However, P-gp is also expressed in normal tissues like the blood-brain barrier, gastrointestinal tract, liver and kidney. It is therefore important to limit the exposure of P-gp inhibitors to normal tissues and increase their co-localization with anticancer agents in tumor tissues to maximize the efficacy of a P-gp inhibitor. To minimize non-specific binding and increase its delivery to tumor tissues, liposomes, self-assembling phospholipid vesicles, were chosen as a drug delivery vehicle. The liposome has been identified as a system capable of carrying molecules with diverse physicochemical properties. It can also alter the pharmacokinetic profile of loaded molecules which is a concern with both tariquidar and paclitaxel. Liposomes can easily be surface-modified rendering them cell-specific as well as organelle-specific. The main objective of present study was to develop an efficient liposomal delivery system which would deliver therapeutic molecules of interest to tumor tissues and avoid interaction with normal tissues. In this study, the co-delivery of tariquidar and paclitaxel into tumor cells to reverse the MDR using long-circulating cationic liposomes was investigated. SKOV-3TR, the resistant variant of SKOV-3 and MCF-7/ADR, the resistant variant of MCF-7 were used as model cell lines. Uniform liposomal formulations were generated with high incorporation efficiency and no apparent decrease in tariquidar potency towards P-gp. Tariquidar- and paclitaxel- co-loaded long-circulating liposomes showed significant re-sensitization of SKOV-3TR and MCF-7/ADR for paclitaxel in vitro. Further modification of these liposomes with antitumor 2C5 resulted

  6. Physicochemical aspects of the liposome-wool interaction in wool dyeing.

    Science.gov (United States)

    Martí, Meritxell; Barsukov, Leonid I; Fonollosa, Jordi; Parra, José Luis; Sukhanov, Stanislav V; Coderch, Luisa

    2004-04-13

    Despite the promising application of liposomes in wool dyeing, little is known about the mechanism of liposome interactions with the wool fiber and dyestuffs. The kinetics of wool dyeing by two dyes, Acid Green 27 (hydrophobic) and Acid Green 25 (hydrophilic), were compared in three experimental protocols: (1) without liposomes, (2) in the presence of phosphatidylcholine (PC) liposomes, and (3) with wool previously treated with PC liposomes. Physicochemical interactions of liposomes with wool fibers were studied under experimental dyeing conditions with particular interest in the liposome affinity to the fiber surface and changes in the lipid composition of the wool fibers. The results obtained indicate that the presence of liposomes favors the retention of these two dyes in the dyeing bath, this effect being more pronounced in case of the hydrophobic dye. Furthermore, the liposome treatment is accompanied by substantial absorption of PC by wool fibers with simultaneous partial solubilization of their polar lipids (more evident at higher temperatures). This may result in structural modification of the cell membrane complex of wool fibers, which could account for a high level of the dye exhaustion observed at the end of the liposome dyeing process.

  7. Effect of chitosan coating on the characteristics of DPPC liposomes

    Directory of Open Access Journals (Sweden)

    Mohsen M. Mady

    2010-07-01

    Full Text Available Because it is both biocompatible and biodegradable, chitosan has been used to provide a protective capsule in new drug formulations. The present work reports on investigations into some of the physicochemical properties of chitosan-coated liposomes, including drug release rate, transmission electron microscopy (TEM, zeta potential and turbidity measurement. It was found that chitosan increases liposome stability during drug release. The coating of DPPC liposomes with a chitosan layer was confirmed by electron microscopy and the zeta potential of liposomes. The coating of liposomes by chitosan resulted in a marginal increase in the size of the liposomes, adding a layer of (92 ± 27.1 nm. The liposomal zeta potential was found to be increasingly positive as chitosan concentration increased from 0.1% to 0.3% (w/v, before stabilising at a relatively constant value. Turbidity studies revealed that the coating of DPPC liposomes with chitosan did not significantly modify the main phase transition temperature of DPPC at examined chitosan concentrations. The appropriate combination of liposomal and chitosan characteristics may produce liposomes with specific, prolonged and controlled release.

  8. Modification of liposomal concentration in liposome/adenoviral complexes allows significant protection of adenoviral vectors from neutralising antibody, in vitro.

    Science.gov (United States)

    Steel, Jason C; Cavanagh, Heather M A; Burton, Mark A; Dingwall, Daniel J; Kalle, Wouter H J

    2005-06-01

    Adenoviral vectors have been commonly used in gene therapy protocols, however the success of their use is often limited by the induction of host immunity to the vector. Following exposure to the adenoviral vector, adenoviral-specific neutralising antibodies are produced which limits further administration. This study examines the efficacy of complexing liposomes to adenovirus for the protection of the adenovirus from neutralising antibodies in an in vitro setting. Dimethyldioctadecylammonium bromide (DDAB)-dioleoyl-l-phosphatidylethanolamine (DOPE) liposomes were bound at varying concentrations to adenovirus to form AL complexes and tested these complexes' ability to prevent adenoviral neutralisation. It is shown that by increasing the concentration of liposomes in the adenoviral-liposome (AL) complexes we can increase the level of immuno-shielding afforded the adenovirus. It is also shown that the increase in liposomal concentration may lead to drawbacks such as increased cytotoxicity and reductions in expression levels.

  9. Characterization of Diclofenac Liposomes Formulated with Palm Oil ...

    African Journals Online (AJOL)

    Purpose: To characterize diclofenac sodium (DS) liposomes prepared using palm oil fractions. Methods: Reverse-phase evaporation method was used to prepare liposomes containing 10, 20, 30 , 40 or 50% palm oil fractions. The effect of palm oil content on liposome formation, surface morphology, shape, size and zeta ...

  10. Filter-extruded liposomes revisited

    DEFF Research Database (Denmark)

    Hinna, Askell; Steiniger, Frank; Hupfeld, Stefan

    2016-01-01

    (pore-size, number of filter passages, and flow-rate), flow field-flow fractionation in conjunction with multi-angle laser light scattering (AF4-MALLS, Wyatt Technology Corp., Santa Barbara, CA) was employed. Liposome size-distributions determined by AF4-MALLS were compared with those of dynamic light...... is suggested to prepare large (300 nm) liposomes with rather narrow size distribution, based on the filter extrusion at defined flow-rates in combination with freeze-/ thaw-cycling and bench-top centrifugation....

  11. Combining different types of multifunctional liposomes loaded with ammonium bicarbonate to fabricate microneedle arrays as a vaginal mucosal vaccine adjuvant-dual delivery system (VADDS).

    Science.gov (United States)

    Wang, Ning; Zhen, Yuanyuan; Jin, Yiguang; Wang, Xueting; Li, Ning; Jiang, Shaohong; Wang, Ting

    2017-01-28

    To develop effective mucosal vaccines, two types of multifunctional liposomes, the mannosylated lipid A-liposomes (MLLs) with a size of 200nm and the stealth lipid A-liposomes (SLLs) of 50nm, both loaded with a model antigen and NH 4 HCO 3 , were fabricated together into microneedles, forming the proSLL/MLL-constituted microneedle array (proSMMA), which upon rehydration dissolved rapidly recovering the initial MLLs and SLLs. Mice vaccinated with proSMMAs by vaginal mucosa patching other than conventional intradermal administration established robust antigen-specific humoral and cellular immunity at both systemic and mucosal levels, especially, in the reproductive and intestinal ducts. Further exploration demonstrated that the MLLs reconstituted from the administered proSMMAs were mostly taken up by vaginal mucosal dendritic cells, whereas the recovered SLLs trafficked directly to draining lymph nodes wherein to be picked up by macrophages. Moreover, the antigens delivered by either liposomes were also cross-presented for MHC-I displaying by APCs thanks to lysosome escape and ROS (reactive oxygen species) stimulation, both of which occurred when lysosomal acidifying the liposome-released NH 4 HCO 3 into CO 2 and NH 4 + /NH 3 to rupture lysosomes by gas expansion and to cause ROS production by excessive ammonia induction, resulting in a mixed Th1/Th2 type response which was also promoted by liposomal lipid A via activation of TLR4. In addition, vaginal vaccination of the engineered HSV2 antigen gD-loaded proSMMAs successfully protected mice from the virus challenge. Thus, the proSMMAs are in fact a vaccine adjuvant-dual delivery system capable of eliciting robust humoral and cellular immunity against the invading pathogens, especially, the sexually transmitted ones. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Optimization and characterization of liposome formulation by mixture design.

    Science.gov (United States)

    Maherani, Behnoush; Arab-tehrany, Elmira; Kheirolomoom, Azadeh; Reshetov, Vadzim; Stebe, Marie José; Linder, Michel

    2012-02-07

    This study presents the application of the mixture design technique to develop an optimal liposome formulation by using the different lipids in type and percentage (DOPC, POPC and DPPC) in liposome composition. Ten lipid mixtures were generated by the simplex-centroid design technique and liposomes were prepared by the extrusion method. Liposomes were characterized with respect to size, phase transition temperature, ζ-potential, lamellarity, fluidity and efficiency in loading calcein. The results were then applied to estimate the coefficients of mixture design model and to find the optimal lipid composition with improved entrapment efficiency, size, transition temperature, fluidity and ζ-potential of liposomes. The response optimization of experiments was the liposome formulation with DOPC: 46%, POPC: 12% and DPPC: 42%. The optimal liposome formulation had an average diameter of 127.5 nm, a phase-transition temperature of 11.43 °C, a ζ-potential of -7.24 mV, fluidity (1/P)(TMA-DPH)((¬)) value of 2.87 and an encapsulation efficiency of 20.24%. The experimental results of characterization of optimal liposome formulation were in good agreement with those predicted by the mixture design technique.

  13. pH and temperature dual-sensitive liposome gel based on novel cleavable mPEG-Hz-CHEMS polymeric vaginal delivery system

    Science.gov (United States)

    Chen, Daquan; Sun, Kaoxiang; Mu, Hongjie; Tang, Mingtan; Liang, Rongcai; Wang, Aiping; Zhou, Shasha; Sun, Haijun; Zhao, Feng; Yao, Jianwen; Liu, Wanhui

    2012-01-01

    Background In this study, a pH and temperature dual-sensitive liposome gel based on a novel cleavable hydrazone-based pH-sensitive methoxy polyethylene glycol 2000-hydrazone-cholesteryl hemisuccinate (mPEG-Hz-CHEMS) polymer was used for vaginal administration. Methods The pH-sensitive, cleavable mPEG-Hz-CHEMS was designed as a modified pH-sensitive liposome that would selectively degrade under locally acidic vaginal conditions. The novel pH-sensitive liposome was engineered to form a thermogel at body temperature and to degrade in an acidic environment. Results A dual-sensitive liposome gel with a high encapsulation efficiency of arctigenin was formed and improved the solubility of arctigenin characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. The dual-sensitive liposome gel with a sol-gel transition at body temperature was degraded in a pH-dependent manner, and was stable for a long period of time at neutral and basic pH, but cleavable under acidic conditions (pH 5.0). Arctigenin encapsulated in a dual-sensitive liposome gel was more stable and less toxic than arctigenin loaded into pH-sensitive liposomes. In vitro drug release results indicated that dual-sensitive liposome gels showed constant release of arctigenin over 3 days, but showed sustained release of arctigenin in buffers at pH 7.4 and pH 9.0. Conclusion This research has shed some light on a pH and temperature dual-sensitive liposome gel using a cleavable mPEG-Hz-CHEMS polymer for vaginal delivery. PMID:22679372

  14. [Preparation of diclofenac sodium liposomes and its ocular pharmacokinetics].

    Science.gov (United States)

    Sun, Kao-xiang; Wang, Ai-ping; Huang, Li-jun; Liang, Rong-cai; Liu, Ke

    2006-11-01

    To prepare diclofenac sodium liposomes and observe its ocular pharmacokinetics in rabbits. The diclofenac sodium cationic liposomes were prepared by reverse-phase evaporation methods and the formula of liposome was optimized with uniform design. HPLC method was established and validated for the determination of diclofenac sodium in precornea, cornea and aqueous humor of rabbit eye. Liposome and eyedrop solution 50 microL with total 50 microg diclofenac sodium were instilled to eyes of rabbits, separately. Samples of tear, cornea and aqueous humor were collected at different time intervals after rabbits were sacrificed. The ocular pharmacokinetics was investigated by the concentration-time data of tear, cornea and aqueous humor. The mean particle size of the diclofenac sodium liposomes was 226.5 nm with zeta potential of + 18. 1 mV. The entrapment efficiency reached 63%. Compared with solution, liposome was characterized by slower clearance in precornea. The concentration of diclotenac in cornea and aqueous humor instilled with liposome were higher than that with eye-drop solution. Cmax of diclofenac sodium in aqueous humor instilled with liposome and eye-drop solution were (0.69 +/- 0.25) and (0.48 +/- 0.19) microg x mL(-1) and (36.68 +/- 11.7) and (21.82 +/- 8.6) microg x g(-1) in cornea, respectively. But no significant difference were found to Tmax in aqueous humor and cornea between liposome and eyedrop, T(1/2) of diclofenac in aqueous humor and cornea with liposoine were longer than that with eye-drop solution. The ocular bioavailability of liposome in aqueous humor was 211% compared with that of eyedrop. Diclofenac sodium cationic liposomes can increase the corneal contact time, enhance the corneal permeability of diclofenac sodium and improve its ocular bioavailability.

  15. Enhancing siRNA-based cancer therapy using a new pH-responsive activatable cell-penetrating peptide-modified liposomal system

    Directory of Open Access Journals (Sweden)

    Xiang B

    2017-03-01

    Full Text Available Bai Xiang,1,* Xue-Li Jia,1,* Jin-Long Qi,2 Li-Ping Yang,1 Wei-Hong Sun,1 Xiao Yan,1 Shao-Kun Yang,1 De-Ying Cao,1 Qing Du,1 Xian-Rong Qi3 1Department of Pharmaceutics, School of Pharmaceutical Sciences, 2Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei, 3School of Pharmaceutical Sciences, Peking University, Beijing, China *These authors contributed equally to this work Abstract: As a potent therapeutic agent, small interfering RNA (siRNA has been exploited to silence critical genes involved in tumor initiation and progression. However, development of a desirable delivery system is required to overcome the unfavorable properties of siRNA such as its high degradability, molecular size, and negative charge to help increase its accumulation in tumor tissues and promote efficient cellular uptake and endosomal/lysosomal escape of the nucleic acids. In this study, we developed a new activatable cell-penetrating peptide (ACPP that is responsive to an acidic tumor microenvironment, which was then used to modify the surfaces of siRNA-loaded liposomes. The ACPP is composed of a cell-penetrating peptide (CPP, an acid-labile linker (hydrazone, and a polyanionic domain, including glutamic acid and histidine. In the systemic circulation (pH 7.4, the surface polycationic moieties of the CPP (polyarginine are “shielded” by the intramolecular electrostatic interaction of the inhibitory domain. When exposed to a lower pH, a common property of solid tumors, the ACPP undergoes acid-catalyzed breakage at the hydrazone site, and the consequent protonation of histidine residues promotes detachment of the inhibitory peptide. Subsequently, the unshielded CPP would facilitate the cellular membrane penetration and efficient endosomal/lysosomal evasion of liposomal siRNA. A series of investigations demonstrated that once exposed to an acidic pH, the ACPP-modified liposomes showed elevated cellular uptake, downregulated expression of polo

  16. Enhancement of anticancer activity in antineovascular therapy is based on the intratumoral distribution of the active targeting carrier for anticancer drugs

    International Nuclear Information System (INIS)

    Maeda, Noriyuki; Miyazawa, Souichiro; Shimizu, Kosuke; Asai, Tomohiro; Yonezawa, Sei; Oku, Naoto; Kitazawa, Sadaya; Namba, Yukihiro; Tsukada, Hideo

    2006-01-01

    We previously observed the enhanced anticancer efficacy of anticancer drugs encapsulated in Ala-Pro-Arg-Pro-Gly-polyethyleneglycol-modified liposome (APRPG-PEG-Lip) in tumor-bearing mice, since APRPG peptide was used as an active targeting tool to angiogenic endothelium. This modality, antineovascular therapy (ANET), aims to eradicate tumor cells indirectly through damaging angiogenic vessels. In the present study, we examined the in vivo trafficking of APRPG-PEG-Lip labeled with [2- 18 F]2-fluoro-2-deoxy- D -glucose ([2- 18 F]FDG) by use of positron emission tomography (PET), and observed that the trafficking of this liposome was quite similar to that of non-targeted long-circulating liposome (PEG-Lip). Then, histochemical analysis of intratumoral distribution of both liposomes was performed by use of fluorescence-labeled liposomes. In contrast to in vivo trafficking, intratumoral distribution of both types of liposomes was quite different: APRPG-PEG-Lip was colocalized with angiogenic endothelial cells that were immunohistochemically stained for CD31, although PEG-Lip was localized around the angiogenic vessels. These results strongly suggest that intratumoral distribution of drug carrier is much more important for therapeutic efficacy than the total accumulation of the anticancer drug in the tumor, and that active delivery of anticancer drugs to angiogenic vessels is useful for cancer treatment. (author)

  17. Targeted delivery of chemically modified anti-miR-221 to hepatocellular carcinoma with negatively charged liposomes

    Directory of Open Access Journals (Sweden)

    Zhang W

    2015-07-01

    Full Text Available Wendian Zhang,1 Fangqi Peng,1 Taotao Zhou,1 Yifei Huang,2 Li Zhang,3 Peng Ye,4 Miao Lu,1 Guang Yang,5 Yongkang Gai,1 Tan Yang,1 Xiang Ma,1 Guangya Xiang1 1School of Pharmacy, Tongji Medical College, 2Department of Pharmacy, 3Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 4Department of Pharmacy, Wuhan University, Renmin Hospital, 5School of Medicine, Jianghan University, Wuhan, People’s Republic of China Abstract: Hepatocellular carcinoma (HCC is one of the leading causes of cancer-related death. Gene therapy was established as a new strategy for treating HCC. To explore the potential delivery system to support the gene therapy of HCC, negatively charged liposomal delivery system was used to deliver miR-221 antisense oligonucleotide (anti-miR-221 to the transferrin (Tf receptor over expressed HepG2 cells. The liposome exhibited a mean particle size of 122.5 nm, zeta potential of -15.74 mV, anti-miR-221 encapsulation efficiency of 70%, and excellent colloidal stability at 4°C. Anti-miR-221-encapsulated Tf-targeted liposome demonstrated a 15-fold higher delivery efficiency compared to nontargeted liposome in HepG2 cells in vitro. Anti-miR-221 Tf-targeted liposome effectively delivered anti-miR-221 to HepG2 cells, upregulated miR-221 target genes PTEN, P27kip1, and TIMP3, and exhibited greater silencing efficiency over nontargeted anti-miR-221 liposome. After intravenous injection into HepG2 tumor-bearing xenografted mice with Cy3-labeled anti-miR-221 Tf-targeted liposome, Cy3-anti-miR-221 was successfully delivered to the tumor site and increased the expressions of PTEN, P27kip1, and TIMP3. Our results demonstrate that the Tf-targeted negatively charged liposome could be a potential therapeutic modality in the gene therapy of human HCC. Keywords: transferrin, gene, HCC, target delivery system, anionic liposome 

  18. Comparative Study between topical applications liposomally entrapped DNA repair enzymes and thymidine dinucleotide as radioprotectors

    International Nuclear Information System (INIS)

    Shabon, M.H.; El-Bedewi, A.F.

    2005-01-01

    The delivery of active agents to the skin by liposome carriers received great interest during the last three decades. This is based on their potential to enclose various types of biological materials and to deliver them to diverse cell types. Recent work suggests that liposomes as vehicles for topical drug delivery may be superior to conventional preparations. Also, topical application of DNA repair enzymes to irradiated skin increases the rate of repair of DNA potentially damaged cells. Moreover, thymidine dinucleotide is a new skin photo-protective agent against non-ionizing radiation through induction of DNA repair. Gamma irradiation can produce DNA damage in human skin. DNA mutations have an important role in the development of skin cancer and precancerous skin lesions. Albino rats were irradiated with Cobalt-60 gamma radiation with different doses (0.5, 1.5, 3 Gy), and were treated by either thymidine dinucleotide or liposomally entrapped DNA repair enzymes topically 24 hours before irradiation. Evaluation was done histopathologically by H and E stain. Computerized image analyzer using Masson's trichrome stain was also done. Gamma radiation produced epidermal thinning and dermal inflammatory cells together with collagen fragmentation and clumping in a dose-dependent manner. Comparing between both thymidine dinucleotide and liposomally entrapped DNA repair enzymes pretreated and irradiated rats. Low dose irradiation (0.5 Gy) together with previous drugs showed preservation of epidermis with no inflammatory cells and also it maintained the normal architecture of collagen bundles. However, they were ineffective with higher doses. In conclusion our results may suggest that the effects of gamma radiation on the skin at low dose could be minimized by the use of these drugs before exposure

  19. Overcoming cellular and tissue barriers to improve liposomal drug delivery

    Science.gov (United States)

    Kohli, Aditya G.

    Forty years of liposome research have demonstrated that the anti-tumor efficacy of liposomal therapies is, in part, driven by three parameters: 1) liposome formulation and lipid biophysics, 2) accumulation and distribution in the tumor, and 3) release of the payload at the site of interest. This thesis outlines three studies that improve on each of these delivery steps. In the first study, we engineer a novel class of zwitterlipids with an inverted headgroup architecture that have remarkable biophysical properties and may be useful for drug delivery applications. After intravenous administration, liposomes accumulate in the tumor by the enhanced permeability and retention effect. However, the tumor stroma often limits liposome efficacy by preventing distribution into the tumor. In the second study, we demonstrate that depletion of hyaluronan in the tumor stroma improves the distribution and efficacy of DoxilRTM in murine 4T1 tumors. Once a liposome has distributed to the therapeutic site, it must release its payload over the correct timescale. Few facile methods exist to quantify the release of liposome therapeutics in vivo. In the third study, we outline and validate a simple, robust, and quantitative method for tracking the rate and extent of release of liposome contents in vivo. This tool should facilitate a better understanding of the pharmacodynamics of liposome-encapsulated drugs in animals. This work highlights aspects of liposome behavior that have prevented successful clinical translation and proposes alternative approaches to improve liposome drug delivery.

  20. On-chip microreactor system for the production of nano-emulsion loaded liposomes: towards targeted delivery of lipophilic drugs

    NARCIS (Netherlands)

    Langelaan, M.L.P.; Emmelkamp, J.; Segers, M.J.A.; Lenting, H.B.M.

    2011-01-01

    An on-chip microreactor system for the production of novel nano-biodevices is presented. This nano-biodevice consists of a nano-emulsion loaded with lipophilic drugs, entrapped in liposomes. These nano-biodevices can be equipped with targeting molecules for higher drug efficiency. The microreactor

  1. Enhanced iron removal from liver parenchymal cells in experimental iron overload: liposome encapsulation of HBED and phenobarbital administration

    International Nuclear Information System (INIS)

    Rahman, Y.E.; Cerny, E.A.; Lau, E.H.; Carnes, B.A.

    1983-01-01

    The effectiveness of N,N'-bis[2-hydroxybenzyl]-ethylene-diamine-N,N'-diacetic acid (HBED) in removing radioiron introduced into the parenchymal cells of mouse liver as 59 Fe-ferritin has been investigated. The effectiveness of HBED, an iron chelator of low water solubility, has also been compared with that of desferrioxamine (DF), an iron chelator of high water solubility and currently in clinical use for treatment of transfusional iron overload. Using the 59 Fe excretion as the measure of effectiveness of chelation therapy and a standardized single chelator dose of 25 mg/kg, they have found that: (1) a saline suspension of HBED, prepared by sonication and given intraperitoneally to mice, promotes a small but significant increase in excretion of radioiron compared to the untreated controls, whereas DF, in its free form, is ineffective; (2) HBED encapsulated in lipid bilayers of liposomes and given intravenously is superior to nonencapsulated HBED; (3) DF encapsulated in small unilamellar liposomes is ineffective in removing iron given in the form of ferritin; (4) administration of phenobarbital in drinking water, at a concentration of 1 g/liter, induces a 30%-55% increase of iron excretion from untreated control mice and also from mice given HBED either in liposome-encapsulated or nonencapsulated form. HBED is superior to DF for removal of storage iron from liver parenchymal cells and liposomes are useful carriers for iron chelators of low water solubility

  2. Calcium-Responsive Liposomes via a Synthetic Lipid Switch.

    Science.gov (United States)

    Lou, Jinchao; Carr, Adam J; Watson, Alexa J; Mattern-Schain, Samuel I; Best, Michael D

    2018-03-07

    Liposomal drug delivery would benefit from enhanced control over content release. Here, we report a novel avenue for triggering release driven by chemical composition using liposomes sensitized to calcium-a target chosen due to its key roles in biology and disease. To demonstrate this principle, we synthesized calcium-responsive lipid switch 1, designed to undergo conformational changes upon calcium binding. The conformational change perturbs membrane integrity, thereby promoting cargo release. This was shown through fluorescence-based release assays via dose-dependent response depending on the percentage of 1 in liposomes, with minimal background leakage in controls. DLS experiments indicated dramatic changes in particle size upon treatment of liposomes containing 1 with calcium. In a comparison of ten naturally occurring metal cations, calcium provided the greatest release. Finally, STEM images showed significant changes in liposome morphology upon treatment of liposomes containing 1 with calcium. These results showcase lipid switches driven by molecular recognition principles as an exciting avenue for controlling membrane properties. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Biomimetics in drug delivery systems: A critical review.

    Science.gov (United States)

    Sheikhpour, Mojgan; Barani, Leila; Kasaeian, Alibakhsh

    2017-05-10

    Today, the advanced drug delivery systems have been focused on targeted drug delivery fields. The novel drug delivery is involved with the improvement of the capacity of drug loading in drug carriers, cellular uptake of drug carriers, and the sustained release of drugs within target cells. In this review, six groups of therapeutic drug carriers including biomimetic hydrogels, biomimetic micelles, biomimetic liposomes, biomimetic dendrimers, biomimetic polymeric carriers and biomimetic nanostructures, are studied. The subject takes advantage of the biomimetic methods of productions or the biomimetic techniques for the surface modifications, similar to what accrues in natural cells. Moreover, the effects of these biomimetic approaches for promoting the drug efficiency in targeted drug delivery are visible. The study demonstrates that the fabrication of biomimetic nanocomposite drug carriers could noticeably promote the efficiency of drugs in targeted drug delivery systems. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Release of Liposomal Contents by Cell-Secreted Matrix Metalloproteinase-9

    Science.gov (United States)

    Banerjee, Jayati; Hanson, Andrea J.; Gadam, Bhushan; Elegbede, Adekunle I.; Tobwala, Shakila; Ganguly, Bratati; Wagh, Anil; Muhonen, Wallace W.; Law, Benedict; Shabb, John B.; Srivastava, D. K.; Mallik, Sanku

    2011-01-01

    Liposomes have been widely used as a drug delivery vehicle and currently, more than 10 liposomal formulations are approved by the Food and Drug Administration for clinical use. However, upon targeting, the release of the liposome-encapsulated contents is usually slow. We have recently demonstrated that contents from appropriately-formulated liposomes can be rapidly released by the cancer-associated enzyme matrix metalloproteinase-9 (MMP-9). Herein, we report our detailed studies to optimize the liposomal formulations. By properly selecting the lipopeptide, the major lipid component and their relative amounts, we demonstrate that the contents are rapidly released in the presence of cancer-associated levels of recombinant human MMP-9. We observed that the degree of lipid mismatch between the lipopepides and the major lipid component profoundly affects the release profiles from the liposomes. By utilizing the optimized liposomal formulations, we also demonstrate that cancer cells (HT-29) which secrete low levels of MMP-9 failed to release significant amount of the liposomal contents. Metastatic cancer cells (MCF7) secreting high levels of the enzyme rapidly release the encapsulated contents from the liposomes. PMID:19601658

  5. Improved Antitumor Efficacy and Pharmacokinetics of Bufalin via PEGylated Liposomes

    Science.gov (United States)

    Yuan, Jiani; Zhou, Xuanxuan; Cao, Wei; Bi, Linlin; Zhang, Yifang; Yang, Qian; Wang, Siwang

    2017-11-01

    Bufalin was reported to show strong pharmacological effects including cardiotonic, antiviral, immune-regulation, and especially antitumor effects. The objective of this study was to determine the characterization, antitumor efficacy, and pharmacokinetics of bufalin-loaded PEGylated liposomes compared with bufalin entity, which were prepared by FDA-approved pharmaceutical excipients. Bufalin-loaded PEGylated liposomes and bufalin-loaded liposomes were prepared reproducibly with homogeneous particle size by the combination of thin film evaporation method and high-pressure homogenization method. Their mean particle sizes were 127.6 and 155.0 nm, mean zeta potentials were 2.24 and - 18.5 mV, and entrapment efficiencies were 76.31 and 78.40%, respectively. In vitro release profile revealed that the release of bufalin in bufalin-loaded PEGylated liposomes was slower than that in bufalin-loaded liposomes. The cytotoxicity of blank liposomes has been found within acceptable range, whereas bufalin-loaded PEGylated liposomes showed enhanced cytotoxicity to U251 cells compared with bufalin entity. In vivo pharmacokinetics indicated that bufalin-loaded PEGylated liposomes could extend or eliminate the half-life time of bufalin in plasma in rats. The results suggested that bufalin-loaded PEGylated liposomes improved the solubility and increased the drug concentration in plasma.

  6. pH-triggered echogenicity and contents release from liposomes.

    Science.gov (United States)

    Nahire, Rahul; Hossain, Rayat; Patel, Rupa; Paul, Shirshendu; Meghnani, Varsha; Ambre, Avinash H; Gange, Kara N; Katti, Kalpana S; Leclerc, Estelle; Srivastava, D K; Sarkar, Kausik; Mallik, Sanku

    2014-11-03

    Liposomes are representative lipid nanoparticles widely used for delivering anticancer drugs, DNA fragments, or siRNA to cancer cells. Upon targeting, various internal and external triggers have been used to increase the rate for contents release from the liposomes. Among the internal triggers, decreased pH within the cellular lysosomes has been successfully used to enhance the rate for releasing contents. However, imparting pH sensitivity to liposomes requires the synthesis of specialized lipids with structures that are substantially modified at a reduced pH. Herein, we report an alternative strategy to render liposomes pH sensitive by encapsulating a precursor which generates gas bubbles in situ in response to acidic pH. The disturbance created by the escaping gas bubbles leads to the rapid release of the encapsulated contents from the liposomes. Atomic force microscopic studies indicate that the liposomal structure is destroyed at a reduced pH. The gas bubbles also render the liposomes echogenic, allowing ultrasound imaging. To demonstrate the applicability of this strategy, we have successfully targeted doxorubicin-encapsulated liposomes to the pancreatic ductal carcinoma cells that overexpress the folate receptor on the surface. In response to the decreased pH in the lysosomes, the encapsulated anticancer drug is efficiently released. Contents released from these liposomes are further enhanced by the application of continuous wave ultrasound (1 MHz), resulting in substantially reduced viability for the pancreatic cancer cells (14%).

  7. Spin Trapping Radicals from Lipid Oxidation in Liposomes in the Presence of Flavonoids

    International Nuclear Information System (INIS)

    Arshad, N.

    2013-01-01

    Interactions of four structurally related flavonoids - quercetin, rutin, morin and catechin with peroxyl radicals using liposome/N-tert-butyl-alpha-phenylnitrone (PBN) and liposome -(4-pyridyl-N-oxide)-N-tert-butylnitrone (POBN)-spin trap systems have been studied through spin trapping ESR. Results obtained were different from that of conjugated diene analysis experiments, where lag phases indicated radical scavenging activity of all the flavonoids. No clear lag phase was observed in ESR experiments under same conditions. In the presence of flavonoids decreasing ESR signals of spin adducts in PBN, while no or negligibly smaller spin adducts with POBN system were observed which may be attributed to the possibility that spin traps interacted with free radicals. Experiments with buffer/spin trap systems without liposome revealed that spin adducts were only stable with catechin and destroyed by quercetin, rutin and morin in buffer/spin trap systems. These results further assured that quercetin, rutin and morin not only interacted with peroxyl radicals but also with spin adducts. (author)

  8. Radioprotective effectiveness of Adeturone incapsulated in liposomes

    International Nuclear Information System (INIS)

    Pantev, T.

    1989-01-01

    The radioprotective properties of the radioprotector Adeturone incapsulated in mono- and tricomponent liposomes were studied. Intraperitoneal administration of the radioprotector by means of monocomponent liposomes from egg lecithin, as well as its applicaton alone immediately (15-30 min) before irradiation of mice with 7,5 Gy gamma-quanta (LD 100/30 ) guaranteed high survival -80% and 75% accordingly. Orally introduced Adeturone, incapsulated in tricomponent liposomes (dipalmitoil lecithin, cholesterol, stearinamine - 7:2:1), protected for 0,5 to 4,5 hours lethally X-irradiated mice (7,8 Gy; LD 90/30 ). Under these conditions, Adeturone applied alone 4,5 hours before irradiation was ineffective. These results show the presence of prolonged radioprotective effect of Adeturone, when orally applied in the form of liposomal suspension. 2 tabs., 17 refs

  9. Copper-64 labeled liposomes for imaging bone marrow

    International Nuclear Information System (INIS)

    Lee, Sang-gyu; Gangangari, Kishore; Kalidindi, Teja Muralidhar; Punzalan, Blesida; Larson, Steven M.; Pillarsetty, Naga Vara Kishore

    2016-01-01

    Introduction: Bone marrow is the soft tissue compartment inside the bones made up of hematopoietic cells, adipocytes, stromal cells, phagocytic cells, stem cells, and sinusoids. While [ 18 F]-FLT has been utilized to image proliferative marrow, to date, there are no reports of particle based positron emission tomography (PET) imaging agents for imaging bone marrow. We have developed copper-64 labeled liposomal formulation that selectively targets bone marrow and therefore serves as an efficient PET probe for imaging bone marrow. Methods: Optimized liposomal formulations were prepared with succinyl PE, DSPC, cholesterol, and mPEG-DSPE (69:39:1:10:0.1) with diameters of 90 and 140 nm, and were doped with DOTA-Bn-DSPE for stable 64 Cu incorporation into liposomes. Results: PET imaging and biodistribution studies with 64 Cu-labeled liposomes indicate that accumulation in bone marrow was as high as 15.18 ± 3.69%ID/g for 90 nm liposomes and 7.01 ± 0.92%ID/g for 140 nm liposomes at 24 h post-administration. In vivo biodistribution studies in tumor-bearing mice indicate that the uptake of 90 nm particles is approximately 0.89 ± 0.48%ID/g in tumor and 14.22 ± 8.07%ID/g in bone marrow, but respective values for Doxil® like liposomes are 0.83 ± 0.49%ID/g and 2.23 ± 1.00%ID/g. Conclusion: Our results indicate that our novel PET labeled liposomes target bone marrow with very high efficiency and therefore can function as efficient bone marrow imaging agents.

  10. The Effects of Lyophilization on the Physico-Chemical Stability of Sirolimus Liposomes

    Directory of Open Access Journals (Sweden)

    Parvin Zakeri-Milani

    2013-02-01

    Full Text Available Purpose: The major limitation in the widespread use of liposome drug delivery system is its instability. Lyophilization is a promising approach to ensure the long-term stability of liposomes. The aim of this study was to prepare sirolimus-loaded liposomes, study their stability and investigate the effect of lyophilization either in the presence or in the absence of lyoprotectant on liposome properties. Methods: Two types of multi-lamellar liposomes, conventional and fusogenic, containing sirolimus were prepared by modified thin film hydration method with different ratio of dipalmitoylphosphatidylcholine (DPPC, cholesterol and dioleoylphosphoethanolamine (DOPE, and were lyophilized with or without dextrose as lyoprotectant. Chemical stability investigation was performed at 4°C and 25°C until 6 months using a validated HPLC method. Physical stability was studied with determination of particle size (PS and encapsulation efficiency (EE % of formulations through 6 months. Results: Chemical stability test at 4°C and 25°C until 6 months showed that drug content of liposomes decreased 8.4% and 20.2% respectively. Initial mean EE % and PS were 72.8 % and 582 nm respectively. After 6 months mean EE % for suspended form, lyophilized without lyoprotectant and lyophilized with lyoprotectant were 54.8 %, 62.3% and 67.1 % at 4°C and 48.2%, 60.4 % and 66.8 % at 25°C respectively. Corresponding data for mean PS were 8229 nm, 2397 nm and 688nm at 4°C and 9362 nm, 1944 nm and 737 nm at 25°C respectively. Conclusion: It is concluded that lyophilization with and without dextrose could increase shelf life of liposome and dextrose has lyoprotectant effect that stabilized liposomes in the lyophilization process.

  11. Preparation and ocular pharmacokinetics of ganciclovir liposomes

    OpenAIRE

    Shen, Yan; Tu, Jiasheng

    2007-01-01

    Ophthalmic liposomes of ganciclovir (GCV) were prepared by the reverse phase evaporation method, and their ocular pharmacokinetics in albino rabbits were compared with those obtained after dosing with GCV solution. The in vitro transcorneal permeability of GCV liposomes was found to be 3.9-fold higher than that of the solution. After in vivo instillation in albino rabbits, no difference was found in the precorneal elimination rate of GCV from liposome vs solution dosing. The aqueous humor con...

  12. The Role of Cavitation in Liposome Formation

    OpenAIRE

    Richardson, Eric S.; Pitt, William G.; Woodbury, Dixon J.

    2007-01-01

    Liposome size is a vital parameter of many quantitative biophysical studies. Sonication, or exposure to ultrasound, is used widely to manufacture artificial liposomes, yet little is known about the mechanism by which liposomes are affected by ultrasound. Cavitation, or the oscillation of small gas bubbles in a pressure-varying field, has been shown to be responsible for many biophysical effects of ultrasound on cells. In this study, we correlate the presence and type of cavitation with a decr...

  13. Targeted Therapy for Acute Autoimmune Myocarditis with Nano-Sized Liposomal FK506 in Rats.

    Directory of Open Access Journals (Sweden)

    Keiji Okuda

    Full Text Available Immunosuppressive agents are used for the treatment of immune-mediated myocarditis; however, the need to develop a more effective therapeutic approach remains. Nano-sized liposomes may accumulate in and selectively deliver drugs to an inflammatory lesion with enhanced vascular permeability. The aims of this study were to investigate the distribution of liposomal FK506, an immunosuppressive drug encapsulated within liposomes, and the drug's effects on cardiac function in a rat experimental autoimmune myocarditis (EAM model. We prepared polyethylene glycol-modified liposomal FK506 (mean diameter: 109.5 ± 4.4 nm. We induced EAM by immunization with porcine myosin and assessed the tissue distribution of the nano-sized beads and liposomal FK506 in this model. After liposomal or free FK506 was administered on days 14 and 17 after immunization, the cytokine expression in the rat hearts along with the histological findings and hemodynamic parameters were determined on day 21. Ex vivo fluorescent imaging revealed that intravenously administered fluorescent-labeled nano-sized beads had accumulated in myocarditic but not normal hearts on day 14 after immunization and thereafter. Compared to the administration of free FK506, FK506 levels were increased in both the plasma and hearts of EAM rats when liposomal FK506 was administered. The administration of liposomal FK506 markedly suppressed the expression of cytokines, such as interferon-γ and tumor necrosis factor-α, and reduced inflammation and fibrosis in the myocardium on day 21 compared to free FK506. The administration of liposomal FK506 also markedly ameliorated cardiac dysfunction on day 21 compared to free FK506. Nano-sized liposomes may be a promising drug delivery system for targeting myocarditic hearts with cardioprotective agents.

  14. Targeted Therapy for Acute Autoimmune Myocarditis with Nano-Sized Liposomal FK506 in Rats.

    Science.gov (United States)

    Okuda, Keiji; Fu, Hai Ying; Matsuzaki, Takashi; Araki, Ryo; Tsuchida, Shota; Thanikachalam, Punniyakoti V; Fukuta, Tatsuya; Asai, Tomohiro; Yamato, Masaki; Sanada, Shoji; Asanuma, Hiroshi; Asano, Yoshihiro; Asakura, Masanori; Hanawa, Haruo; Hao, Hiroyuki; Oku, Naoto; Takashima, Seiji; Kitakaze, Masafumi; Sakata, Yasushi; Minamino, Tetsuo

    2016-01-01

    Immunosuppressive agents are used for the treatment of immune-mediated myocarditis; however, the need to develop a more effective therapeutic approach remains. Nano-sized liposomes may accumulate in and selectively deliver drugs to an inflammatory lesion with enhanced vascular permeability. The aims of this study were to investigate the distribution of liposomal FK506, an immunosuppressive drug encapsulated within liposomes, and the drug's effects on cardiac function in a rat experimental autoimmune myocarditis (EAM) model. We prepared polyethylene glycol-modified liposomal FK506 (mean diameter: 109.5 ± 4.4 nm). We induced EAM by immunization with porcine myosin and assessed the tissue distribution of the nano-sized beads and liposomal FK506 in this model. After liposomal or free FK506 was administered on days 14 and 17 after immunization, the cytokine expression in the rat hearts along with the histological findings and hemodynamic parameters were determined on day 21. Ex vivo fluorescent imaging revealed that intravenously administered fluorescent-labeled nano-sized beads had accumulated in myocarditic but not normal hearts on day 14 after immunization and thereafter. Compared to the administration of free FK506, FK506 levels were increased in both the plasma and hearts of EAM rats when liposomal FK506 was administered. The administration of liposomal FK506 markedly suppressed the expression of cytokines, such as interferon-γ and tumor necrosis factor-α, and reduced inflammation and fibrosis in the myocardium on day 21 compared to free FK506. The administration of liposomal FK506 also markedly ameliorated cardiac dysfunction on day 21 compared to free FK506. Nano-sized liposomes may be a promising drug delivery system for targeting myocarditic hearts with cardioprotective agents.

  15. Ex vivo skin delivery of diclofenac by transcutol containing liposomes and suggested mechanism of vesicle-skin interaction.

    Science.gov (United States)

    Manconi, Maria; Caddeo, Carla; Sinico, Chiara; Valenti, Donatella; Mostallino, Maria Cristina; Biggio, Giovanni; Fadda, Anna Maria

    2011-05-01

    Recently, we described a novel family of liposomes, the Penetration Enhancer-containing Vesicles (PEVs), as carriers for enhanced (trans)dermal drug delivery. In this study, to go deeply into the potential of these new vesicles and suggest the possible mechanism of vesicle-skin interaction, we investigated transcutol containing PEVs as carriers for diclofenac, in the form of either acid or sodium salt. PEVs, prepared with soy phosphatidylcholine and aqueous solutions containing different concentrations of transcutol, were characterized by size distribution, zeta potential, incorporation efficiency, thermotropic behavior, and stability. (Trans)dermal diclofenac delivery from PEVs was investigated ex vivo through new born pig skin using conventional liposomes and a commercial gel as controls. The mode of action of the vesicles was also studied by performing a pre-treatment test and confocal laser scanning microscopy (CLSM) analyses. Results of the all skin permeation experiments showed an improved diclofenac (both acid and sodium salt) delivery to and through the skin when PEVs were used (especially in comparison with the commercial gel) thus suggesting intact PEVs' penetration through the pig skin. Images of the qualitative CLSM analyses support this conclusion. Thus, this work shows the superior ability of the PEVs to enhance ex vivo drug transport of both hydrophilic and lipophilic diclofenac forms. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Clearance and localization of intravitreal liposomes in the aphakic vitrectomized eye

    International Nuclear Information System (INIS)

    Stern, W.H.; Heath, T.D.; Lewis, G.P.; Guerin, C.J.; Erickson, P.A.; Lopez, N.G.; Hong, K.L.

    1987-01-01

    The authors have examined the fate of intravitreally injected liposomes in the aphakic, vitrectomized eye of the rabbit. Liposomes labelled with 125 [I]-p-hydroxybenzimidylphosphatidylethanolamine were eliminated rapidly from the intraocular fluid. Nonetheless, a significant fraction of these liposomes were found to bind to various ocular tissues including the retina, iris, sclera, and cornea. Ultrastructural studies with gold colloid-loaded liposomes revealed that retinal bound liposomes were attached to the inner limiting lamina but did not penetrate to the internal cells of the retina. Epiretinal cells bound and internalized gold colloid-loaded liposomes suggesting that these cells may be very sensitive to liposome mediated drug delivery

  17. Ultrasound-mediated drug delivery using liposomes modified with a thermosensitive polymer.

    Science.gov (United States)

    Ninomiya, Kazuaki; Kawabata, Shinya; Tashita, Hiroyuki; Shimizu, Nobuaki

    2014-01-01

    Ultrasound-mediated drug delivery was established using liposomes that were modified with the thermosensitive polymer (TSP) poly(NIPMAM-co-NIPAM), which sensitized the liposomes to high temperatures. TSP-modified liposomes (TSP liposomes) released encapsulated calcein under 1 MHz ultrasound irradiation at 0.5 W/cm(2) for 120 s as well as the case under incubation at 42 °C for 15 min. In addition, uptake of the drug released from TSP liposomes by cancer cells was enhanced by ultrasound irradiation. In a cell injury assay using doxorubicin (DOX)-loaded TSP liposomes and ultrasound irradiation, cell viability of HepG2 cells at 6 h after ultrasound irradiation (1 MHz, 0.5 W/cm(2) for 30 s) with DOX-loaded TSP liposomes (TSP/lipid ratio=1) was 60%, which was significantly lower than that of the control conditions such as DOX-loaded TSP liposomes alone and DOX-loaded intact liposomes under ultrasound irradiation. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Liposomal clodronate selectively eliminates microglia from primary astrocyte cultures

    Directory of Open Access Journals (Sweden)

    Kumamaru Hiromi

    2012-05-01

    Full Text Available Abstract Background There is increasing interest in astrocyte biology because astrocytes have been demonstrated to play prominent roles in physiological and pathological conditions of the central nervous system, including neuroinflammation. To understand astrocyte biology, primary astrocyte cultures are most commonly used because of the direct accessibility of astrocytes in this system. However, this advantage can be hindered by microglial contamination. Although several authors have warned regarding microglial contamination in this system, complete microglial elimination has never been achieved. Methods The number and proliferative potential of contaminating microglia in primary astrocyte cultures were quantitatively assessed by immunocytologic and flow cytometric analyses. To examine the utility of clodronate for microglial elimination, primary astrocyte cultures or MG-5 cells were exposed to liposomal or free clodronate, and then immunocytologic, flow cytometric, and gene expression analyses were performed. The gene expression profiles of microglia-eliminated and microglia-contaminated cultures were compared after interleukin-6 (IL-6 stimulation. Results The percentage of contaminating microglia exceeded 15% and continued to increase because of their high proliferative activity in conventional primary astrocyte cultures. These contaminating microglia were selectively eliminated low concentration of liposomal clodronate. Although primary microglia and MG-5 cells were killed by both liposomal and free clodronate, free clodronate significantly affected the viability of astrocytes. In contrast, liposomal clodronate selectively eliminated microglia without affecting the viability, proliferation or activation of astrocytes. The efficacy of liposomal clodronate was much higher than that of previously reported methods used for decreasing microglial contamination. Furthermore, we observed rapid tumor necrosis factor-α and IL-1b gene induction in

  19. Rational design of liposomal drug delivery systems, a review: Combined experimental and computational studies of lipid membranes, liposomes and their PEGylation

    Czech Academy of Sciences Publication Activity Database

    Bunker, A.; Magarkar, Aniket; Viitala, T.

    2016-01-01

    Roč. 1858, č. 10 (2016), s. 2334-2352 ISSN 0005-2736 Institutional support: RVO:61388963 Keywords : nanomedicine * liposome * drug delivery * molecular dynamics simulation * label-free analytics * PEGylation Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.498, year: 2016

  20. Methods for using redox liposome biosensors

    Science.gov (United States)

    Cheng, Quan; Stevens, Raymond C.

    2002-01-01

    The present invention provides methods and compositions for detecting the presence of biologically-important analytes by using redox liposome biosensors. In particular, the present invention provides liposome/sol-gel electrodes suitable for the detection of a wide variety of organic molecules, including but not limited to bacterial toxins.

  1. ANTISTAPHYLOCOCCAL ACTIVITY OF LIPOSOMAL FORMS OF LINCOMYCIN

    Directory of Open Access Journals (Sweden)

    Derkach SA

    2015-04-01

    Full Text Available Nowadays the vital problem of modern medicine is a tendency to emerging of both nosocomial and community-acquired strains before antibiotic resistance forming. The complexity of antibiotic therapy of diseases caused by methicillin resistant staphylococci having high poly resistance almost to every classes of antibacterial agents is of prime importance. One of the ways to improve antibacterial preparations still remains the development of their liposomal forms. This work studies antistaphylococcal activity (according to MIC of the liposomal form of lincomycin developed in the Institute of Dermatology and Venereology of Ukraine by Ivanova N. N., the Candidate of Сhemical Sciences.The purpose of this research work was to study liposomal inhibiting concentration of the liposomalny form of lincomycin and a commercial preparation lincomycin (produced by CJSC “Pharmaceutical firm "Darnitsa". Determination of the minimum inhibiting concentration was carried out by a tablet micromethod by consecutive cultivations of the samples under study.It is shown that MIC of liposomal lincomycin is eight times as low as usual lincomycin (0,23mkg/ml to 1,87 mkg/ml. Antibacterial activity of the liposomal form of lincomycin is studied concerning the patients selected from the different biotopes with pyo inflammatory diseases of staphylococcus strains (15 strains – methicillin sensitive, 12 strains - methicillin resistant.It is shown authentically the higher sensitivity of S. aureus strains to the liposomal form of lincomycin in comparison with usual lincomycin . Also 50.0% of MRSA strains were sensitive to the liposomalny form of lincomycin that shows the perspective for the development of the liposomal forms of antibiotics to cure staphylococcal infections.

  2. Development and pharmacokinetic of antimony encapsulated in liposomes of phosphatidylserine using radioisotopes in experimental leishmaniasis

    International Nuclear Information System (INIS)

    Borborema, Samanta Etel Treiger

    2010-01-01

    Leishmaniasis are a complex of parasitic diseases caused by intra macrophage protozoa of the genus Leishmania, and is fatal if left untreated. Pentavalent antimonials, though toxic and their mechanism of action being unclear, remain the first-line drugs for treatment. Effective therapy could be achieved by delivering antileishmanial drugs to these sites of infection. Liposomes are phospholipid vesicles that promote improvement in the efficacy and action of drugs in target cell. Liposomes are taken up by the cells of mononuclear phagocytic system (MPS). The purpose of this study was to develop a preparation of meglumine antimonate encapsulated in liposomes of phosphatidylserine and to study its pharmacokinetic in healthy mice to establish its metabolism and distribution. Quantitative analysis of antimony from liposomes demonstrated that Neutron Activation Analysis was the most sensitive technique with almost 100 % of accuracy. All liposome formulations presented a mean diameter size of 150 nm. The determination of IC 50 in infected macrophage showed that liposome formulations were between 10 - 63 fold more effective than the free drug, indicating higher selectivity index. By fluorescence microscopy, an increased uptake of fluorescent-liposomes was seen in infected macrophages during short times of incubation compared with non-infected macrophages. Biodistribution studies showed that meglumine antimonate irradiated encapsulated in liposomes of phosphatidylserine promoted a targeting of antimony for MPS tissues and maintained high doses in organs for a prolonged period. In conclusion, these data suggest that meglumine antimonate encapsulated in liposomes showed higher effectiveness than the non-liposomal drug against Leishmania infection. The development of liposome formulations should be a new alternative for the chemotherapy of infection diseases, especially Leishmaniasis, as they are used to sustain and target pharmaceuticals to the local of infection. (author)

  3. Polylactic acid (PLA) controlled delivery carriers for biomedical applications.

    Science.gov (United States)

    Tyler, Betty; Gullotti, David; Mangraviti, Antonella; Utsuki, Tadanobu; Brem, Henry

    2016-12-15

    Polylactic acid (PLA) and its copolymers have a long history of safety in humans and an extensive range of applications. PLA is biocompatible, biodegradable by hydrolysis and enzymatic activity, has a large range of mechanical and physical properties that can be engineered appropriately to suit multiple applications, and has low immunogenicity. Formulations containing PLA have also been Food and Drug Administration (FDA)-approved for multiple applications making PLA suitable for expedited clinical translatability. These biomaterials can be fashioned into sutures, scaffolds, cell carriers, drug delivery systems, and a myriad of fabrications. PLA has been the focus of a multitude of preclinical and clinical testing. Three-dimensional printing has expanded the possibilities of biomedical engineering and has enabled the fabrication of a myriad of platforms for an extensive variety of applications. PLA has been widely used as temporary extracellular matrices in tissue engineering. At the other end of the spectrum, PLA's application as drug-loaded nanoparticle drug carriers, such as liposomes, polymeric nanoparticles, dendrimers, and micelles, can encapsulate otherwise toxic hydrophobic anti-tumor drugs and evade systemic toxicities. The clinical translation of these technologies from preclinical experimental settings is an ever-evolving field with incremental advancements. In this review, some of the biomedical applications of PLA and its copolymers are highlighted and briefly summarized. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Liposomal Drug Product Development and Quality: Current US Experience and Perspective.

    Science.gov (United States)

    Kapoor, Mamta; Lee, Sau L; Tyner, Katherine M

    2017-05-01

    Research in the area of liposomes has grown substantially in the past few decades. Liposomes are lipid bilayer structures that can incorporate drug substances to modify the drug's pharmacokinetic profile thereby improving drug delivery. The agency has received over 400 liposomal drug product submissions (excluding combination therapies), and there are currently eight approved liposomal drug products on the US market. In order to identify the pain points in development and manufacturing of liposomal drug products, a retrospective analysis was performed from a quality perspective on submissions for new and generic liposomal drug products. General analysis on liposomal drug product submissions was also performed. Results indicated that 96% of the submissions were Investigational New Drug (IND) applications, 3% were New Drug Applications (NDAs), and the remaining 1% was Abbreviated New Drug Applications (ANDAs). Doxorubicin hydrochloride was the most commonly used drug substance incorporated into the liposomes (31%). The majority of the liposomal products were administered via intravenous route (84%) with cancer (various types) being the most common indication (63%). From a quality perspective, major challenges during the development of liposomal drug products included identification and (appropriate) characterization of critical quality attributes of liposomal drug products and suitable control strategies during product development. By focusing on these areas, a faster and more efficient development of liposomal drug products may be achieved. Additionally, in this way, the drug review process for such products can be streamlined.

  5. Multifunctional liposomes for MRI and image-guided drug delivery

    NARCIS (Netherlands)

    Langereis, Sander; Hijnen, Nicole; Strijkers, Gustav; Nicolay, Klaas; Grüll, Holger

    2014-01-01

    Liposomes are a class of nanovesicles that have been explored extensively in the biomedical arena for early diagnosis and treatment of disease. In recent years, several liposomal drug formulations have been clinically approved in oncology. In a modular approach, the properties of liposomes can be

  6. Astragaloside IV liposomes ameliorates adriamycin-induced ...

    African Journals Online (AJOL)

    Methods: The rats were given a single tail intravenous injection of adriamycin (6 mg/kg) within 1 week, and then divided into four groups including normal, model, benazepril and astragaloside IV liposomes group. They were all orally administered dosage of benazepril and astragaloside IV liposomes once daily for 8 weeks.

  7. 42 CFR 405.512 - Carriers' procedural terminology and coding systems.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Carriers' procedural terminology and coding systems... Determining Reasonable Charges § 405.512 Carriers' procedural terminology and coding systems. (a) General. Procedural terminology and coding systems are designed to provide physicians and third party payers with a...

  8. Atmospheric-pressure guided streamers for liposomal membrane disruption

    International Nuclear Information System (INIS)

    Svarnas, P.; Aleiferis, Sp.; Matrali, S. H.; Gazeli, K.; Clément, F.; Antimisiaris, S. G.

    2012-01-01

    The potential to use liposomes (LIPs) as a cellular model in order to study interactions of cold atmospheric-pressure plasma with cells is herein investigated. Cold atmospheric-pressure plasma is formed by a dielectric-barrier discharge reactor. Large multilamellar vesicle liposomes, consisted of phosphatidylcholine and cholesterol, are prepared by the thin film hydration technique, to encapsulate a small hydrophilic dye, i.e., calcein. The plasma-induced release of calcein from liposomes is then used as a measure of liposome membrane integrity and, consequently, interaction between the cold atmospheric plasma and lipid bilayers. Physical mechanisms leading to membrane disruption are suggested, based on the plasma characterization including gas temperature calculation.

  9. Construction of a Liposome Dialyzer for preparation of high-value, small-volume liposome formulations

    OpenAIRE

    Adamala, Katarzyna; Engelhart, Aaron E.; Kamat, Neha P.; Jin, Lin; Szostak, Jack W.

    2015-01-01

    The liposome dialyzer is a small-volume equilibrium dialysis device, built from commercially available materials, that is designed for rapid exchange of small volumes of an extraliposomal reagent pool against a liposome preparation. The dialyzer is prepared by modification of commercially available dialysis cartridges and consists of a reactor with two 300 µL chambers and a 1.56 cm2 dialysis surface area. The dialyzer is prepared in three stages: 1) disassembly of dialysis cartridges to obtai...

  10. Rapid delivery of small interfering RNA by biosurfactant MEL-A-containing liposomes.

    Science.gov (United States)

    Inoh, Yoshikazu; Furuno, Tadahide; Hirashima, Naohide; Kitamoto, Dai; Nakanishi, Mamoru

    2011-10-28

    The downregulation of gene expression by RNA interference holds great potential for genetic analysis and gene therapy. However, a more efficient delivery system for small interfering RNA (siRNA) into the target cells is required for wide fields such as cell biology, physiology, and clinical application. Non-viral vectors are stronger candidates than viral vectors because they are safer and easier to prepare. We have previously used a new method for gene transfection by combining cationic liposomes with the biosurfactant mannosylerythritol lipid-A (MEL-A). The novel MEL-A-containing cationic liposomes rapidly delivered DNA (plasmids and oligonucleotides) into the cytosol and nucleus through membrane fusion between liposomes and the plasma membrane, and consequently, enhanced the gene transfection efficiency. In this study, we determined the efficiency of MEL-A-containing cationic liposomes for siRNA delivery. We observed that exogenous and endogenous protein expression was suppressed by approximately 60% at 24h after brief (30 min) incubation of target cells with MEL-A-containing cationic liposome/siRNA complexes. Confocal microscopic analysis showed that suppression of protein expression was caused by rapid siRNA delivery into the cytosol. We found that the MEL-A-containing cationic liposomes directly delivered siRNA into the cytoplasm by the membrane fusion in addition to endocytotic pathway whereas Lipofectamine RNAiMax delivered siRNA only by the endocytotic pathway. It seems that the ability to rapidly and directly deliver siRNA into the cytosol using MEL-A-containing cationic liposomes is able to reduce immune responses, cytotoxicity, and other side effects caused by viral vectors in clinical applications. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Sulfocerebrosides upregulate liposome uptake in human astrocytes without inducing a proinflammatory response.

    Science.gov (United States)

    Suesca, Elizabeth; Alejo, Jose Luis; Bolaños, Natalia I; Ocampo, Jackson; Leidy, Chad; González, John M

    2013-07-01

    Astrocytes are involved in the pathogenesis of demyelinating diseases, where they actively regulate the secretion of proinflammatory factors, and trigger the recruitment of immune cells in the central nervous system (CNS). Antigen presentation of myelin-derived proteins has been shown to trigger astrocyte response, suggesting that astrocytes can directly sense demyelination. However, the direct response of astrocytes to lipid-debris generated during demyelination has not been investigated. The lipid composition of the myelin sheath is distinct, presenting significant amounts of cerebrosides, sulfocerebrosides (SCB), and ceramides. Studies have shown that microglia are activated in the presence of myelin-derived lipids, pointing to the possibility of lipid-induced astrocyte activation. In this study, a human astrocyte cell line was exposed to liposomes enriched in each myelin lipid component. Although liposome uptake was observed for all compositions, astrocytes had augmented uptake for liposomes containing sulfocerebroside (SCB). This enhanced uptake did not modify their expression of human leukocyte antigen (HLA) molecules or secretion of chemokines. This was in contrast to changes observed in astrocyte cells stimulated with IFNγ. Contrary to human monocytes, astrocytes did not internalize beads in the size-range of liposomes, indicating that liposome uptake is lipid specific. Epifluorescence microscopy corroborated that liposome uptake takes place through endocytosis. Soluble SCB were found to partially block uptake of liposomes containing this same lipid. Endocytosis was not decreased when cells were treated with cytochalasin D, but it was decreased by cold temperature incubation. The specific uptake of SCB in the absence of a proinflammatory response indicates that astrocytes may participate in the trafficking and regulation of sulfocerebroside metabolism and homeostasis in the CNS. Copyright © 2013 International Society for Advancement of Cytometry.

  12. Radiolabeling, biodistribution and tumor imaging of stealth liposomes containing methotrexate

    International Nuclear Information System (INIS)

    Subramanian, N; Arulsudar, N; Chuttani, K; Mishra, P; Sharma, R.K; Murthy, R.S.R

    2003-01-01

    To study the utility of sterically stabilized liposomes (stealth liposomes) in tumor scintigraphy by studying its biodistribution and accumulation in target tissue after radiolabeling with Technetium-99m (99mTC). Conventional and Stealth liposomes were prepared by lipid film hydration method using methotrexate as model anticancer drug. Radiolabeling of the liposomes was carried out by direct labeling using reduced 99mTc. Experimental conditions for maximum labeling yield were optimized. The stability studies were carried out to check binding strength of the radiolabeled complexes. The blood kinetic study was carried out in rabbits after giving the labeled complex by intravenous administration through ear vein. The biodistribution studies were carried out in the Ehrlich ascites tumor (EAT) bearing mice after intravenous administration through tail vein, showed prolonged circulation in blood and significant increase in the accumulation in tumor for the sterically stabilized liposomes compared to the conventional liposomes. The gamma scintigraphic image shows the distribution of the stealth liposomes in liver, spleen, kidney and tumor. The study gives precise idea about the use of stealth liposomes in tumor scintigraphy and organ distribution studies (Au)

  13. Interactions of a Photochromic Spiropyran with Liposome Model Membranes

    KAUST Repository

    Jonsson, Fabian

    2013-02-19

    The interactions between anionic or zwitterionic liposomes and a water-soluble, DNA-binding photochromic spiropyran are studied using UV/vis absorption and linear dichroism (LD) spectroscopy. The spectral characteristics as well as the kinetics of the thermal isomerization process in the absence and presence of the two different liposome types provide information about the environment and whether or not the spiropyran resides in the liposome membrane. By measuring LD on liposomes deformed and aligned by shear flow, further insight is obtained about interaction and binding geometry of the spiropyran at the lipid membranes. We show that the membrane interactions differ between the two types of liposomes used as well as the isomeric forms of the spiropyran photoswitch. © 2013 American Chemical Society.

  14. Recent Trends in Multifunctional Liposomal Nanocarriers for Enhanced Tumor Targeting

    Directory of Open Access Journals (Sweden)

    Federico Perche

    2013-01-01

    Full Text Available Liposomes are delivery systems that have been used to formulate a vast variety of therapeutic and imaging agents for the past several decades. They have significant advantages over their free forms in terms of pharmacokinetics, sensitivity for cancer diagnosis and therapeutic efficacy. The multifactorial nature of cancer and the complex physiology of the tumor microenvironment require the development of multifunctional nanocarriers. Multifunctional liposomal nanocarriers should combine long blood circulation to improve pharmacokinetics of the loaded agent and selective distribution to the tumor lesion relative to healthy tissues, remote-controlled or tumor stimuli-sensitive extravasation from blood at the tumor’s vicinity, internalization motifs to move from tumor bounds and/or tumor intercellular space to the cytoplasm of cancer cells for effective tumor cell killing. This review will focus on current strategies used for cancer detection and therapy using liposomes with special attention to combination therapies.

  15. Antibody-Hapten Recognition at the Surface of Functionalized Liposomes Studied by SPR: Steric Hindrance of Pegylated Phospholipids in Stealth Liposomes Prepared for Targeted Radionuclide Delivery

    Directory of Open Access Journals (Sweden)

    Eliot. P. Botosoa

    2011-01-01

    Full Text Available Targeted PEGylated liposomes could increase the amount of drugs or radionuclides delivered to tumor cells. They show favorable stability and pharmacokinetics, but steric hindrance of the PEG chains can block the binding of the targeting moiety. Here, specific interactions between an antihapten antibody (clone 734, specific for the DTPA-indium complex and DTPA-indium-tagged liposomes were characterized by surface plasmon resonance (SPR. Non-PEGylated liposomes fused on CM5 chips whereas PEGylated liposomes did not. By contrast, both PEGylated and non-PEGylated liposomes attached to L1 chips without fusion. SPR binding kinetics showed that, in the absence of PEG, the antibody binds the hapten at the surface of lipid bilayers with the affinity of the soluble hapten. The incorporation of PEGylated lipids hinders antibody binding to extents depending on PEGylated lipid fraction and PEG molecular weight. SPR on immobilized liposomes thus appears as a useful technique to optimize formulations of liposomes for targeted therapy.

  16. Progress involving new techniques for liposome preparation

    Directory of Open Access Journals (Sweden)

    Zhenjun Huang

    2014-08-01

    Full Text Available The article presents a review of new techniques being used for the preparation of liposomes. A total of 28 publications were examined. In addition to the theories, characteristics and problems associated with traditional methods, the advantages and drawbacks of the latest techniques were reviewed. In the light of developments in many relevant areas, a variety of new techniques are being used for liposome preparation and each of these new technique has particular advantages over conventional preparation methods. However, there are still some problems associated with these new techniques that could hinder their applications and further improvements are needed. Generally speaking, due to the introduction of these latest techniques, liposome preparation is now an improved procedure. These applications promote not only advances in liposome research but also the methods for their production on an industrial scale.

  17. Cytoprotective and enhanced anti-inflammatory activities of liposomal piroxicam formulation in lipopolysaccharide-stimulated RAW 264.7 macrophages.

    Science.gov (United States)

    Chiong, Hoe Siong; Yong, Yoke Keong; Ahmad, Zuraini; Sulaiman, Mohd Roslan; Zakaria, Zainul Amiruddin; Yuen, Kah Hay; Hakim, Muhammad Nazrul

    2013-01-01

    Liposomal drug delivery systems, a promising lipid-based nanoparticle technology, have been known to play significant roles in improving the safety and efficacy of an encapsulated drug. Liposomes, prepared using an optimized proliposome method, were used in the present work to encapsulate piroxicam, a widely prescribed nonsteroidal anti-inflammatory drug. The cytotoxic effects as well as the in vitro efficacy in regulation of inflammatory responses by free-form piroxicam and liposome-encapsulated piroxicam were evaluated using a lipopolysaccharide-sensitive macrophage cell line, RAW 264.7. Cells treated with liposome-encapsulated piroxicam demonstrated higher cell viabilities than those treated with free-form piroxicam. In addition, the liposomal piroxicam formulation resulted in statistically stronger inhibition of pro-inflammatory mediators (ie, nitric oxide, tumor necrosis factor-α, interleukin-1β, and prostaglandin E2) than piroxicam at an equivalent dose. The liposome-encapsulated piroxicam also caused statistically significant production of interleukin-10, an anti-inflammatory cytokine. This study affirms the potential of a liposomal piroxicam formulation in reducing cytotoxicity and enhancing anti-inflammatory responses in vitro.

  18. The Treatment of Breast Cancer Using Liposome Technology

    Directory of Open Access Journals (Sweden)

    Sarah Brown

    2012-01-01

    Full Text Available Liposome-based chemotherapeutics used in the treatment of breast cancer can in principle enhance the therapeutic index of otherwise unencapsulated anticancer drugs. This is partially attributed to the fact that encapsulation of cytotoxic agents within liposomes allows for increased concentrations of the drug to be delivered to the tumor site. In addition, the presence of the phospholipid bilayer prevents the encapsulated active form of the drug from being broken down in the body prior to reaching tumor tissue and also serves to minimize exposure of the drug to healthy sensitive tissue. While clinically approved liposome-based chemotherapeutics such as Doxil have proven to be quite effective in the treatment of breast cancer, significant challenges remain involving poor drug transfer between the liposome and cancerous cells. In this review, we discuss the recent advancements made in the development of liposome-based chemotherapeutics with respect to improved drug transfer for use in breast cancer therapy.

  19. Ultrasound triggered drug delivery with liposomal nested microbubbles.

    Science.gov (United States)

    Wallace, N; Wrenn, S P

    2015-12-01

    When ultrasound contrast agent microbubbles are nested within a liposome, damage to the liposome membrane caused by both stable and inertial cavitation of the microbubble allows for release of the aqueous core of the liposome. Triggered release was not accomplished unless microbubbles were present within the liposome. Leakage was tested using fluorescence assays developed specifically for this drug delivery vehicle and qualitative measurements using an optical microscope. These studies were done using a 1 MHz focused ultrasound transducer while varying parameters including peak negative ultrasound pressure, average liposome diameter, and microbubble concentration. Two regimes exist for membrane disruption caused by cavitating microbubbles. A faster release rate, as well as permanent membrane damage are seen for samples exposed to high pressure (2.1-3.7 MPa). A slower release rate and dilation/temporary poration are characteristic of stable cavitation for low pressure studies (0.54-1.7 MPa). Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Body distributioin of RGD-mediated liposome in brain-targeting drug delivery.

    Science.gov (United States)

    Qin, Jing; Chen, DaWei; Hu, Haiyang; Qiao, MingXi; Zhao, XiuLi; Chen, Baoyu

    2007-09-01

    RGD conjugation liposomes (RGD-liposomes) were evaluated for brain-targeting drug delivery. The flow cytometric in vitro study demonstrated that RGD-liposomes could bind to monocytes and neutrophils effectively. Ferulic acid (4-hydroxy-3-methoxycinnamic, FA) was loaded into liposomes. Rats were subjected to intrastriatal microinjections of 100 units of human recombinant IL-1beta to produce brain inflammation and caudal vein injection of three formulations (FA solution, FA liposome and RGD-coated FA liposome). Animals were sacrificed 15, 30, 60 and 120 min after administration to study the body distribution of the FA in the three formulations. HPLC was used to determine the concentration of FA in vivo with salicylic acid as internal standard. The results of body distribution indicated that RGD-coated liposomes could be mediated into the brain with a 6-fold FA concentration compared to FA solution and 3-fold in comparison to uncoated liposome. Brain targeted delivery was achieved and a reduction in dosage might be allowed.

  1. Application of multifunctional targeting epirubicin liposomes in the treatment of non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Song X

    2017-10-01

    Full Text Available Xiao-li Song,1 Rui-jun Ju,2 Yao Xiao,1 Xin Wang,1 Shuang Liu,1 Min Fu,1 Jing-jing Liu,1 Li-yan Gu,1 Xue-tao Li,1 Lan Cheng1 1School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 2Department of Pharmaceutical Engineering, Beijing Institute of Petrochemical Technology, Beijing, China Abstract: Chemotherapy for aggressive non-small-cell lung cancer (NSCLC usually results in a poor prognosis due to tumor metastasis, vasculogenic mimicry (VM channels, limited killing of tumor cells, and severe systemic toxicity. Herein, we developed a kind of multifunctional targeting epirubicin liposomes to enhance antitumor efficacy for NSCLC. In the liposomes, octreotide was modified on liposomal surface for obtaining a receptor-mediated targeting effect, and honokiol was incorporated into the lipid bilayer for inhibiting tumor metastasis and eliminating VM channels. In vitro cellular assays showed that multifunctional targeting epirubicin liposomes not only exhibited the strongest cytotoxic effect on Lewis lung tumor cells but also showed the most efficient inhibition on VM channels. Action mechanism studies showed that multifunctional targeting epirubicin liposomes could downregulate PI3K, MMP-2, MMP-9, VE-Cadherin, and FAK and activate apoptotic enzyme caspase 3. In vivo results exhibited that multifunctional targeting epirubicin liposomes could accumulate selectively in tumor site and display an obvious antitumor efficacy. In addition, no significant toxicity of blood system and major organs was observed at a test dose. Therefore, multifunctional targeting epirubicin liposomes may provide a safe and efficient therapy strategy for NSCLC. Keywords: octreotide, honokiol, chemotherapy, vasculogenic mimicry, tumor metastasis, targeting drug delivery

  2. HER2-targeted liposomal doxorubicin displays enhanced anti-tumorigenic effects without associated cardiotoxicity

    International Nuclear Information System (INIS)

    Reynolds, Joseph G.; Geretti, Elena; Hendriks, Bart S.; Lee, Helen; Leonard, Shannon C.; Klinz, Stephan G.; Noble, Charles O.; Lücker, Petra B.; Zandstra, Peter W.; Drummond, Daryl C.; Olivier, Kenneth J.; Nielsen, Ulrik B.; Niyikiza, Clet; Agresta, Samuel V.; Wickham, Thomas J.

    2012-01-01

    Anthracycline-based regimens are a mainstay of early breast cancer therapy, however their use is limited by cardiac toxicity. The potential for cardiotoxicity is a major consideration in the design and development of combinatorial therapies incorporating anthracyclines and agents that target the HER2-mediated signaling pathway, such as trastuzumab. In this regard, HER2-targeted liposomal doxorubicin was developed to provide clinical benefit by both reducing the cardiotoxicity observed with anthracyclines and enhancing the therapeutic potential of HER2-based therapies that are currently available for HER2-overexpressing cancers. While documenting the enhanced therapeutic potential of HER2-targeted liposomal doxorubicin can be done with existing models, there has been no validated human cardiac cell-based assay system to rigorously assess the cardiotoxicity of anthracyclines. To understand if HER2-targeting of liposomal doxorubicin is possible with a favorable cardiac safety profile, we applied a human stem cell-derived cardiomyocyte platform to evaluate the doxorubicin exposure of human cardiac cells to HER2-targeted liposomal doxorubicin. To the best of our knowledge, this is the first known application of a stem cell-derived system for evaluating preclinical cardiotoxicity of an investigational agent. We demonstrate that HER2-targeted liposomal doxorubicin has little or no uptake into human cardiomyocytes, does not inhibit HER2-mediated signaling, results in little or no evidence of cardiomyocyte cell death or dysfunction, and retains the low penetration into heart tissue of liposomal doxorubicin. Taken together, this data ultimately led to the clinical decision to advance this drug to Phase I clinical testing, which is now ongoing as a single agent in HER2-expressing cancers. -- Highlights: ► Novel approach using stem cell-derived cardiomyocytes to assess preclinical safety. ► HER2-targeted liposomal doxorubicin has improved safety profile vs free doxorubicin

  3. HER2-targeted liposomal doxorubicin displays enhanced anti-tumorigenic effects without associated cardiotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, Joseph G.; Geretti, Elena; Hendriks, Bart S.; Lee, Helen; Leonard, Shannon C.; Klinz, Stephan G.; Noble, Charles O. [Merrimack Pharmaceuticals, 1 Kendall Square, Suite B7201, Cambridge, MA 02139 (United States); Lücker, Petra B.; Zandstra, Peter W. [University of Toronto, 160 College Street, Office 1116, Toronto, Ontario M5S 3E1 (Canada); Drummond, Daryl C.; Olivier, Kenneth J.; Nielsen, Ulrik B.; Niyikiza, Clet; Agresta, Samuel V. [Merrimack Pharmaceuticals, 1 Kendall Square, Suite B7201, Cambridge, MA 02139 (United States); Wickham, Thomas J., E-mail: twickham@merrimackpharma.com [Merrimack Pharmaceuticals, 1 Kendall Square, Suite B7201, Cambridge, MA 02139 (United States)

    2012-07-01

    Anthracycline-based regimens are a mainstay of early breast cancer therapy, however their use is limited by cardiac toxicity. The potential for cardiotoxicity is a major consideration in the design and development of combinatorial therapies incorporating anthracyclines and agents that target the HER2-mediated signaling pathway, such as trastuzumab. In this regard, HER2-targeted liposomal doxorubicin was developed to provide clinical benefit by both reducing the cardiotoxicity observed with anthracyclines and enhancing the therapeutic potential of HER2-based therapies that are currently available for HER2-overexpressing cancers. While documenting the enhanced therapeutic potential of HER2-targeted liposomal doxorubicin can be done with existing models, there has been no validated human cardiac cell-based assay system to rigorously assess the cardiotoxicity of anthracyclines. To understand if HER2-targeting of liposomal doxorubicin is possible with a favorable cardiac safety profile, we applied a human stem cell-derived cardiomyocyte platform to evaluate the doxorubicin exposure of human cardiac cells to HER2-targeted liposomal doxorubicin. To the best of our knowledge, this is the first known application of a stem cell-derived system for evaluating preclinical cardiotoxicity of an investigational agent. We demonstrate that HER2-targeted liposomal doxorubicin has little or no uptake into human cardiomyocytes, does not inhibit HER2-mediated signaling, results in little or no evidence of cardiomyocyte cell death or dysfunction, and retains the low penetration into heart tissue of liposomal doxorubicin. Taken together, this data ultimately led to the clinical decision to advance this drug to Phase I clinical testing, which is now ongoing as a single agent in HER2-expressing cancers. -- Highlights: ► Novel approach using stem cell-derived cardiomyocytes to assess preclinical safety. ► HER2-targeted liposomal doxorubicin has improved safety profile vs free doxorubicin

  4. Efficient intradermal delivery of superoxide dismutase using a combination of liposomes and iontophoresis for protection against UV-induced skin damage.

    Science.gov (United States)

    Kigasawa, Kaoru; Miyashita, Moeko; Kajimoto, Kazuaki; Kanamura, Kiyoshi; Harashima, Hideyoshi; Kogure, Kentaro

    2012-01-01

    Superoxide dismutase (SOD) is a potent antioxidant agent that protects against UV-induced skin damage. However, its high molecular weight is a significant obstacle for efficient delivery into the skin through the stratum corneum and development of antioxidant activity. Recently, we developed a non-invasive transfollicular delivery system for macromolecules using a combination of liposomes and iontophoresis, that represents promising technology for enhancing transdermal administration of charged drugs (IJP, 403, 2011, Kajimoto et al.). In this study, in rats we attempted to apply this system to intradermal delivery of SOD for preventing UV-induced skin injury. SOD encapsulating in cationic liposomes was subjected to anodal iontophoresis. After iontophoretic treatment, the liposomes were diffused widely in the viable skin layer around hair follicles. In contrast, passive diffusion failed to transport liposomes efficiently into the skin. Iontophoretic delivery of liposomes encapsulating SOD caused a marked decrease in the production of oxidative products, such as malondialdehyde, hexanoyl lysine, and 8-hydroxi-2-deoxyguanosine, in UV-irradiated skin. These findings suggested that functional SOD can be delivered into the skin using a combination of iontophoresis and a liposomal system. In conclusion, we succeeded in developing an efficient intradermal SOD delivery system, that would be useful for delivery of other macromolecules.

  5. Liposomal encapsulated Zn-DTPA for removing intracellular 169Yb

    International Nuclear Information System (INIS)

    Blank, M.L.; Cress, E.A.; Byrd, B.L.; Washburn, L.C.; Snyder, F.

    1980-01-01

    Multilamellar liposomes possessing neutral positive or negative charges were tested for their capacity to encapsulate sodium ethylenediaminetetraacetate (EDTA) and for their selectivity in depositing in specific tissues after being injected into rats. Negative-charged liposomes had the greatest trapping efficiency over a wide range of lipid-to-aqueous phase ratios. In contrast, except for lung, liposomal charge had no significant effect on the tissue distribution of encapsulated EDTA; liver and spleen exhibited the highest uptake with all preparations. The proportion of encapsulated EDTA taken up by the liver decreased as the amount of injected liposomes was increased. Free zinc diethylenetriaminepentaacetate (Zn-DTPA) and multilamellar liposomes containing entrapped Zn-DTPA were administered to rats that had been injected with 169 Yb-citrate 24 hr earlier. At doses of 14 mg Zn-DTPA per kg body weight, both free Zn-DPTA and the liposomal-bound Zn-DTPA caused increased removal of 169 Yb from the animals. However, treatment with the liposomal Zn-DTPA caused significantly more of the 169 Yb to be removed than did the free Zn-DTPA treatment by itself. Our data indicate that lipophilic forms of chelators can effectively increase the removal rates of heavy metal contamination in tissues. (author)

  6. Heparin octasaccharide decoy liposomes inhibit replication of multiple viruses

    Science.gov (United States)

    Hendricks, Gabriel L.; Velazquez, Lourdes; Pham, Serena; Qaisar, Natasha; Delaney, James C.; Viswanathan, Karthik; Albers, Leila; Comolli, James C.; Shriver, Zachary; Knipe, David M.; Kurt-Jones, Evelyn A.; Fygenson, Deborah K.; Trevejo, Jose M.

    2016-01-01

    Heparan sulfate (HS) is a ubiquitous glycosaminoglycan that serves as a cellular attachment site for a number of significant human pathogens, including respiratory syncytial virus (RSV), human parainfluenza virus 3 (hPIV3), and herpes simplex virus (HSV). Decoy receptors can target pathogens by binding to the receptor pocket on viral attachment proteins, acting as ‘molecular sinks’ and preventing the pathogen from binding to susceptible host cells. Decoy receptors functionalized with HS could bind to pathogens and prevent infection, so we generated decoy liposomes displaying HS-octasaccharide (HS-octa). These decoy liposomes significantly inhibited RSV, hPIV3, and HSV infectivity in vitro to a greater degree than the original HS-octa building block. The degree of inhibition correlated with the density of HS-octa displayed on the liposome surface. Decoy liposomes with HS-octa inhibited infection of viruses to a greater extent than either full-length heparin or HS-octa alone. Decoy liposomes were effective when added prior to infection or following the initial infection of cells in vitro. By targeting the well-conserved receptor-binding sites of HS-binding viruses, decoy liposomes functionalized with HS-octa are a promising therapeutic antiviral agent and illustrate the utility of the liposome delivery platform. PMID:25637710

  7. Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Irma Pujol-Autonell

    Full Text Available The development of new therapies to induce self-tolerance has been an important medical health challenge in type 1 diabetes. An ideal immunotherapy should inhibit the autoimmune attack, avoid systemic side effects and allow β-cell regeneration. Based on the immunomodulatory effects of apoptosis, we hypothesized that apoptotic mimicry can help to restore tolerance lost in autoimmune diabetes.To generate a synthetic antigen-specific immunotherapy based on apoptosis features to specifically reestablish tolerance to β-cells in type 1 diabetes.A central event on the surface of apoptotic cells is the exposure of phosphatidylserine, which provides the main signal for efferocytosis. Therefore, phosphatidylserine-liposomes loaded with insulin peptides were generated to simulate apoptotic cells recognition by antigen presenting cells. The effect of antigen-specific phosphatidylserine-liposomes in the reestablishment of peripheral tolerance was assessed in NOD mice, the spontaneous model of autoimmune diabetes. MHC class II-peptide tetramers were used to analyze the T cell specific response after treatment with phosphatidylserine-liposomes loaded with peptides.We have shown that phosphatidylserine-liposomes loaded with insulin peptides induce tolerogenic dendritic cells and impair autoreactive T cell proliferation. When administered to NOD mice, liposome signal was detected in the pancreas and draining lymph nodes. This immunotherapy arrests the autoimmune aggression, reduces the severity of insulitis and prevents type 1 diabetes by apoptotic mimicry. MHC class II tetramer analysis showed that peptide-loaded phosphatidylserine-liposomes expand antigen-specific CD4+ T cells in vivo. The administration of phosphatidylserine-free liposomes emphasizes the importance of phosphatidylserine in the modulation of antigen-specific CD4+ T cell expansion.We conclude that this innovative immunotherapy based on the use of liposomes constitutes a promising strategy for

  8. Protective Effect of Liposome-Encapsulated Glutathione in a Human Epidermal Model Exposed to a Mustard Gas Analog

    Directory of Open Access Journals (Sweden)

    Victor Paromov

    2011-01-01

    Full Text Available Sulfur mustard or mustard gas (HD and its monofunctional analog, 2-chloroethyl ethyl sulfide (CEES, or “half-mustard gas,” are alkylating agents that induce DNA damage, oxidative stress, and inflammation. HD/CEES are rapidly absorbed in the skin causing extensive injury. We hypothesize that antioxidant liposomes that deliver both water-soluble and lipid-soluble antioxidants protect skin cells from immediate CEES-induced damage via attenuating oxidative stress. Liposomes containing water-soluble antioxidants and/or lipid-soluble antioxidants were evaluated using in vitro model systems. Initially, we found that liposomes containing encapsulated glutathione (GSH-liposomes increased cell viability and attenuated production of reactive oxygen species (ROS in HaCaT cells exposed to CEES. Next, GSH-liposomes were tested in a human epidermal model, EpiDerm. In the EpiDerm, GSH-liposomes administered simultaneously or 1 hour after CEES exposure (2.5 mM increased cell viability, inhibited CEES-induced loss of ATP and attenuated changes in cellular morphology, but did not reduce caspase-3 activity. These findings paralleled the previously described in vivo protective effect of antioxidant liposomes in the rat lung and established the effectiveness of GSH-liposomes in a human epidermal model. This study provides a rationale for use of antioxidant liposomes against HD toxicity in the skin considering further verification in animal models exposed to HD.

  9. siRNA-loaded liposomes: Inhibition of encystment of Acanthamoeba and toxicity on the eye surface.

    Science.gov (United States)

    Faber, Kathrin; Zorzi, Giovanni K; Brazil, Nathalya T; Rott, Marilise B; Teixeira, Helder F

    2017-09-01

    Current treatments for Acanthamoeba keratitis are unspecific. Because of the presence of the resilient cyst form of the parasite, the infection is persistent. Silencing the key protein of cyst formation, glycogen phosphorylase, has shown potential for reducing encystment processes of the Acanthamoeba trophozoite. However, a suitable carrier to protect and deliver siRNA sequences is still needed. DOPE:DSPE-PEG liposomes were prepared by three different techniques and used to associate a therapeutic siRNA sequence. Liposomes prepared by film hydration followed by membrane extrusion were considered the most adequate ones with average size of 250 nm and zeta potential of +45 mV, being able to associate siRNA for at least 24 hr in culture medium. siRNA-liposomes could inhibit up to 66% of the encystment process. Cell viability studies demonstrated MTT reduction capacity higher than 80% after 3 hr incubation with this formulation. After 24 hr of incubation, LDH activity ranged for both the formulations from around 4% to 40%. In vivo tolerance studies in mice showed no macroscopic alteration in the eye structures up to 24 hr after eight administrations during 1 day. Histological studies showed regular tissue architecture without any morphological alteration. Overall, these results suggest that the formulations developed are a promising new strategy for the treatment of ocular keratitis caused by Acanthamoeba spp. © 2017 John Wiley & Sons A/S.

  10. Novel liposomal technology applied in esophageal cancer treatment

    Science.gov (United States)

    Yeh, Chia-Hsien; Hsieh, Yei-San; Yang, Pei-wen; Huang, Leaf; Hsu, Yih-Chih

    2018-02-01

    Cisplatin (CDDP) has been commonly used as a chemotherapeutic drug, mainly used for the treatment of malignant epithelial cell tumors. We have developed a new method based on innovative lipid calcium phosphate, which encapsulated hydrophobic drugs to form liposomal nanoparticles. Esophageal cancer xenograft model was used to investigate the efficacy of liposomal nanoparticles. and it showed good therapeutic efficacy with lower side effects. Liposomal nanoparticles exhibited a better therapeutic effect than that of conventional CDDP.

  11. The Role of Liposomal Bupivacaine in Value-Based Care.

    Science.gov (United States)

    Iorio, Richard

    Multimodal pain control strategies are crucial in reducing opioid use and delivering effective pain management to facilitate improved surgical outcomes. The utility of liposomal bupivacaine in enabling effective pain control in multimodal strategies has been demonstrated in several studies, but others have found the value of liposomal bupivacaine in such approaches to be insignificant. At New York University Langone Medical Center, liposomal bupivacaine injection and femoral nerve block were compared in their delivery of efficacious and cost-effective multimodal analgesia among patients undergoing total joint arthroplasty (TJA). Retrospective analysis revealed that including liposomal bupivacaine in a multimodal pain control protocol for TJA resulted in improved quality and efficiency metrics, decreased narcotic use, and faster mobilization, all relative to femoral nerve block, and without a significant increase in admission costs. In addition, liposomal bupivacaine use was associated with elimination of the need for patient-controlled analgesia in TJA. Thus, at Langone Medical Center, the introduction of liposomal bupivacaine to TJA has been instrumental in achieving adequate pain control, delivering high-level quality of care, and controlling costs.

  12. Immunogenicity of diphtheria toxoid and poly(I:C) loaded cationic liposomes after hollow microneedle-mediated intradermal injection in mice.

    Science.gov (United States)

    Du, Guangsheng; Leone, Mara; Romeijn, Stefan; Kersten, Gideon; Jiskoot, Wim; Bouwstra, Joke A

    2018-06-02

    In this study, we aimed to investigate the immunogenicity of cationic liposomes loaded with diphtheria toxoid (DT) and poly(I:C) after hollow microneedle-mediated intradermal vaccination in mice. The following liposomal formulations were studied: DT loaded liposomes, a mixture of free DT and poly(I:C)-loaded liposomes, a mixture of DT-loaded liposomes and free poly(I:C), and liposomal formulations with DT and poly(I:C) either individually or co-encapsulated in the liposomes. Reference groups were DT solution adjuvanted with or without poly(I:C) (DT/poly(I:C)). The liposomal formulations were characterized in terms of particle size, zeta potential, loading and release of DT and poly(I:C). After intradermal injection of BALB/c mice with the formulations through a hollow microneedle, the immunogenicity was assessed by DT-specific ELISAs. All formulations induced similar total IgG and IgG1 titers. However, all the liposomal groups containing both DT and poly(I:C) showed enhanced IgG2a titers compared to DT/poly(I:C) solution, indicating that the immune response was skewed towards a Th1 direction. This enhancement was similar for all liposomal groups that contain both DT and poly(I:C) in the formulations. Our results reveal that a mixture of DT encapsulated liposomes and poly(I:C) encapsulated liposomes have a similar effect on the antibody responses as DT and poly(I:C) co-encapsulated liposomes. These findings may have implications for future design of liposomal vaccine delivery systems. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Treatment of Digital Ischemia with Liposomal Bupivacaine

    Directory of Open Access Journals (Sweden)

    José Raul Soberón

    2014-01-01

    Full Text Available Objective. This report describes a case in which the off-label use of liposomal bupivacaine (Exparel in a peripheral nerve block resulted in marked improvement of a patient’s vasoocclusive symptoms. The vasodilating and analgesic properties of liposomal bupivacaine in patients with ischemic symptoms are unknown, but our clinical experience suggests a role in the management of patients suffering from vasoocclusive disease. Case Report. A 45-year-old African American female was admitted to the hospital with severe digital ischemic pain. She was not a candidate for any vascular surgical or procedural interventions. Two continuous supraclavicular nerve blocks were placed with modest clinical improvement. These effects were also short-lived, with the benefits resolving after the discontinuation of the peripheral nerve blocks. She continued to report severe pain and was on multiple anticoagulant medications, so a decision was made to perform an axillary nerve block using liposomal bupivacaine (Exparel given the compressibility of the site as well as the superficial nature of the target structures. Conclusions. This case report describes the successful off-label usage of liposomal bupivacaine (Exparel in a patient with digital ischemia. Liposomal bupivacaine (Exparel is currently FDA approved only for wound infiltration use at this time.

  14. Liposome imaging agents in personalized medicine

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa; Hansen, Anders Elias; Gabizon, Alberto

    2012-01-01

    In recent years the importance of molecular and diagnostic imaging has increased dramatically in the treatment planning of many diseases and in particular in cancer therapy. Within nanomedicine there are particularly interesting possibilities for combining imaging and therapy. Engineered liposomes...... that selectively localize in tumor tissue can transport both drugs and imaging agents, which allows for a theranostic approach with great potential in personalized medicine. Radiolabeling of liposomes have for many years been used in preclinical studies for evaluating liposome in vivo performance and has been...... start to consider how to use imaging for patient selection and treatment monitoring in connection to nanocarrier based medicines. Nanocarrier imaging agents could furthermore have interesting properties for disease diagnostics and staging. Here, we review the major advances in the development...

  15. Revisiting nanoparticle technology for blood-brain barrier transport: Unfolding at the endothelial gate improves the fate of transferrin receptor-targeted liposomes.

    Science.gov (United States)

    Johnsen, Kasper Bendix; Moos, Torben

    2016-01-28

    An unmet need exists for therapeutic compounds to traverse the brain capillary endothelial cells that denote the blood-brain barrier (BBB) to deliver effective treatment to the diseased brain. The use of nanoparticle technology for targeted delivery to the brain implies that targeted liposomes encapsulating a drug of interest will undergo receptor-mediated uptake and transport through the BBB with a subsequent unfolding of the liposomal content inside the brain, hence revealing drug release to adjacent drug-demanding neurons. As transferrin receptors (TfRs) are present on brain capillary endothelial, but not on endothelial cells elsewhere in the body, the use of TfR-targeted liposomes - colloidal particulates with a phospholipid bilayer membrane - remains the most relevant strategy to obtain efficient drug delivery to the brain. However, many studies have failed to provide sufficient quantitative data to proof passage of the BBB and significant appearance of drugs inside the brain parenchyma. Here, we critically evaluate the current evidence on the use of TfR-targeted liposomes for brain drug delivery based on a thorough investigation of all available studies within this research field. We focus on issues with respect to experimental design and data analysis that may provide an explanation to conflicting reports, and we discuss possible explanations for the current lack of sufficient transcytosis across the BBB for implementation in the design of TfR-targeted liposomes. We finally provide a list of suggestions for strategies to obtain substantial uptake and transport of drug carriers at the BBB with a concomitant transport of therapeutics into the brain. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Lateral Tension-Induced Penetration of Particles into a Liposome

    Directory of Open Access Journals (Sweden)

    Kazuki Shigyou

    2017-07-01

    Full Text Available It is important that we understand the mechanism of the penetration of particles into a living cell to achieve advances in bionanotechnology, such as for treatment, visualization within a cell, and genetic modification. Although there have been many studies on the application of functional particles to cells, the basic mechanism of penetration across a biological membrane is still poorly understood. Here we used a model membrane system to demonstrate that lateral membrane tension drives particle penetration across a lipid bilayer. After the application of osmotic pressure, fully wrapped particles on a liposome surface were found to enter the liposome. We discuss the mechanism of the tension-induced penetration in terms of narrow constriction of the membrane at the neck part. The present findings are expected to provide insight into the application of particles to biological systems.

  17. Biophysical characterization of V3-lipopeptide liposomes influencing HIV-1 infectivity

    International Nuclear Information System (INIS)

    Rizos, Apostolos K.; Baritaki, Stavroula; Tsikalas, Ioannis; Doetschman, David C.; Spandidos, Demetrios A.; Krambovitis, Elias

    2007-01-01

    The V3-loop of the HIV-1 gp120 alters host cell immune function and modulates infectivity. We investigated biophysical parameters of liposome constructs with embedded lipopeptides from the principle neutralizing domain of the V3-loop and their influence on viral infectivity. Dynamic light scattering measurements showed liposome supramolecular structures with hydrodynamic radius of the order of 900 and 1300 nm for plain and V3-lipopeptide liposomes. Electron paramagnetic resonance measurements showed almost identical local microenvironment. The difference in liposome hydrodynamic radius was attributed to the fluctuating ionic environment of the V3-lipopeptide liposomes. In vitro HIV-1 infectivity assays showed that plain liposomes reduced virus production in all cell cultures, probably due to the hydrophobic nature of the aggregates. Liposomes carrying V3-lipopeptides with different cationic potentials restored and even enhanced infectivity (p < 0.05). These results highlight the need for elucidation of the involvement of lipid bilayers as dynamic components in supramolecular structures and in HIV-1 fusion mechanisms

  18. Syntheses and characterization of liposome-incorporated adamantyl aminoguanidines.

    Science.gov (United States)

    Šekutor, Marina; Štimac, Adela; Mlinarić-Majerski, Kata; Frkanec, Ruža

    2014-08-21

    A series of mono and bis-aminoguanidinium adamantane derivatives has been synthesized and incorporated into liposomes. They combine two biomedically significant molecules, the adamantane moiety and the guanidinium group. The adamantane moiety possesses the membrane compatible features while the cationic guanidinium subunit was recognized as a favourable structural feature for binding to complementary molecules comprising phosphate groups. The liposome formulations of adamantyl aminoguanidines were characterized and it was shown that the entrapment efficiency of the examined compounds is significant. In addition, it was demonstrated that liposomes with incorporated adamantyl aminoguanidines effectively recognized the complementary liposomes via the phosphate group. These results indicate that adamantane derivatives bearing guanidinium groups might be versatile tools for biomedical application, from studies of molecular recognition processes to usage in drug formulation and cell targeting.

  19. Interactive transport of guanidinylated poly(propylene imine)-based dendrimers through liposomal and cellular membranes.

    Science.gov (United States)

    Tsogas, Ioannis; Sideratou, Zili; Tsiourvas, Dimitris; Theodossiou, Theodossis A; Paleos, Constantinos M

    2007-10-15

    The ability of guanidinylated poly(propylene imine) dendrimers to translocate across lipid bilayers was assessed by employing either a model phosphate-bearing liposomal membrane system or A549 human lung carcinoma cells. Two dendrimer generations, differing in the number of surface guanidinium groups, were employed, while surface acetylation or the use of spacers affected the binding of the guanidinium group to the phosphate moiety and finally the transport efficiency. Following adhesion of dendrimers with liposomes, fusion or transport occurred. Transport through the liposomal bilayer was observed at low guanidinium/phosphate molar ratios, and was enhanced when the bilayer was in the liquid-crystalline phase. For effective transport through the liposomal membrane, an optimum balance between the binding strength and the degree of hydrophobicity of the guanidinylated dendrimer is required. In experiments performed in vitro with cells, efficient penetration and internalization in subcellular organelles and cytosol was observed.

  20. Preparation, characterization and in vitro antimicrobial activity of liposomal ceftazidime and cefepime against Pseudomonas aeruginosa strains

    Science.gov (United States)

    Torres, Ieda Maria Sapateiro; Bento, Etiene Barbosa; Almeida, Larissa da Cunha; de Sá, Luisa Zaiden Carvalho Martins; Lima, Eliana Martins

    2012-01-01

    Pseudomonas aeruginosa is an opportunistic microorganism with the ability to respond to a wide variety of environmental changes, exhibiting a high intrinsic resistance to a number of antimicrobial agents. This low susceptibility to antimicrobial substances is primarily due to the low permeability of its outer membrane, efflux mechanisms and the synthesis of enzymes that promote the degradation of these drugs. Cephalosporins, particularty ceftazidime and cefepime are effective against P. aeruginosa, however, its increasing resistance has limited the usage of these antibiotics. Encapsulating antimicrobial drugs into unilamellar liposomes is an approach that has been investigated in order to overcome microorganism resistance. In this study, antimicrobial activity of liposomal ceftazidime and cefepime against P. aeruginosa ATCC 27853 and P. aeruginosa SPM-1 was compared to that of the free drugs. Liposomal characterization included diameter, encapsulation efficiency and stability. Minimum Inhibitory Concentration (MIC) was determined for free and liposomal forms of both drugs. Minimum Bactericidal Concentration (MBC) was determined at concentrations 1, 2 and 4 times MIC. Average diameter of liposomes was 131.88 nm and encapsulation efficiency for cefepime and ceftazidime were 2.29% end 5.77%, respectively. Improved stability was obtained when liposome formulations were prepared with a 50% molar ratio for cholesterol in relation to the phospholipid. MIC for liposomal antibiotics for both drugs were 50% lower than that of the free drug, demonstrating that liposomal drug delivery systems may contribute to increase the antibacterial activity of these drugs. PMID:24031917

  1. In situ SAXS experiment during DNA and liposome complexation

    Energy Technology Data Exchange (ETDEWEB)

    Gasperini, A.A.; Cavalcanti, L.P. [Laboratorio Nacional de Luz Sincrotron (LNLS), Campinas, SP (Brazil); Balbino, T.A.; Torre, L.G. de la [Universidade Estadual de Campinas (UNICAMP), SP (Brazil); Oliveira, C.L.P. [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil)

    2012-07-01

    Full text: Gene therapy is an exciting research area that allows the treatment of different diseases. Basically, an engineered DNA that codes a protein is the therapeutic drug that has to be delivered to the cell nucleus. After that, the DNA transfection process allows the protein production using the cell machinery. However, the efficient delivery needs DNA protection against nucleases and interstitial fluids. In this context, the use of cationic liposome/DNA complexes is a promising strategy for non-viral gene therapy. Liposomes are lipid systems that self-aggregate in bilayers and the use of cationic lipids allows the electrostatic complexation with DNA. In this work, we used SAXS technique to study the complexation kinetics between cationic liposomes and plasmid DNA and evaluate the liposome structural modifications in the presence of DNA. Liposomes were prepared according to [1] using as plasmid DNA vector model a modified version of pVAX1-GFP with luciferase as reporter gene [2]. The complexation was promoted in a SAXS sample holder containing a microchannel to get access to the compartment between two mica windows where the X-ray beam could cross through [3]. We obtained in situ complexation using such sample holder coupled to a fed-batch reactor through a peristaltic pump. The scattering curves were recorded each 30 seconds during the cycles. The DNA was added until a certain final ratio between surface charges previously determined. We studied the form and structure factor model for the liposome bilayer to fit the scattering curves [4]. Structural information such as the bilayer electronic density profiles, number of bilayers and fluidity were determined as a function of the complexation with DNA. These differences can reflect in singular in vitro and in vivo effects. [1] L. G. de la Torre et al. Colloids and Surfaces B: Biointerfaces, 73, 175 (2009) [2] A. R. Azzoni et al. The Journal of Gene Medicine, 9, 392 (2007) [3] L. P. Cavalcanti et al. Review of

  2. Synthesis of diethylenetriaminepentaacetic acid conjugated inulin and utility for cellular uptake of liposomes

    International Nuclear Information System (INIS)

    Essien, H.; Lai, J.Y.; Hwang, K.J.

    1988-01-01

    The synthesis, binding of radioactive cations, liposomal encapsulation, and biodistribution of the oxidized-inulin reaction product with ethylenediamine and diethylenetriaminepentaacetic acid (4) are described. The four-step synthesis of the inulin derivative proceeded in a good overall yield of 72%. The complex of the inulin derivative with either 67 Ga3+ or 111 In3+ was stable in vivo and did not readily distribute into tissues, being excreted primarily in urine after intravenous administration to mice. The liposome-entrapped inulin derivative can be loaded with radioactive heavy metal cations by mobile ionophores in high radiochemical yields of 80-91%. Following the intravenous administration of the liposomal encapsulation of the indium-111-labeled inulin derivative, the entrapped compound had a biodistribution characteristic of liposomes and allowed an estimation of the extent of the intracellular uptake of liposomes. The ability of the inulin derivative to chelate many different types of metals will allow the use of this probe for studying subtle differences in tissue distribution resulting from different drug targeting or delivery protocols in the same animal by multiple labeling techniques. Moreover, the chelate-conjugated inulin permits studies of the applications of drug delivery systems in primates or human subjects by noninvasive techniques such as gamma-scintigraphic or nuclear magnetic resonance imaging methods

  3. Complement activation as a bioequivalence issue relevant to the development of generic liposomes and other nanoparticulate drugs

    Energy Technology Data Exchange (ETDEWEB)

    Szebeni, Janos, E-mail: jszebeni2@gmail.com [Nanomedicine Research and Education Center, Semmelweis University, Budapest & SeroScience Ltd, Budapest (Hungary); Storm, Gert [Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht (Netherlands)

    2015-12-18

    Liposomes are known to activate the complement (C) system, which can lead in vivo to a hypersensitivity syndrome called C activation-related pseudoallergy (CARPA). CARPA has been getting increasing attention as a safety risk of i.v. therapy with liposomes, whose testing is now recommended in bioequivalence evaluations of generic liposomal drug candidates. This review highlights the adverse consequences of C activation, the unique symptoms of CARPA triggered by essentially all i.v. administered liposomal drugs, and the various features of vesicles influencing this adverse immune effect. For the case of Doxil, we also address the mechanism of C activation and the opsonization vs. long circulation (stealth) paradox. In reviewing the methods of assessing C activation and CARPA, we delineate the most sensitive porcine model and an algorithm for stepwise evaluation of the CARPA risk of i.v. liposomes, which are proposed for standardization for preclinical toxicology evaluation of liposomal and other nanoparticulate drug candidates. - Highlights: • Outlining of difficulties in generic development of liposomal drugs. • New regulatory requirements to evaluate CARPA in preclinical studies. • Review of complement activation by liposomes and its adverse consequences (CARPA). • Assays of C activation in vitro and CARPA in vivo, with the porcine test in focus. • Decision tree how to handle the risk of CARPA assessed by a battery of tests.

  4. Complement activation as a bioequivalence issue relevant to the development of generic liposomes and other nanoparticulate drugs

    International Nuclear Information System (INIS)

    Szebeni, Janos; Storm, Gert

    2015-01-01

    Liposomes are known to activate the complement (C) system, which can lead in vivo to a hypersensitivity syndrome called C activation-related pseudoallergy (CARPA). CARPA has been getting increasing attention as a safety risk of i.v. therapy with liposomes, whose testing is now recommended in bioequivalence evaluations of generic liposomal drug candidates. This review highlights the adverse consequences of C activation, the unique symptoms of CARPA triggered by essentially all i.v. administered liposomal drugs, and the various features of vesicles influencing this adverse immune effect. For the case of Doxil, we also address the mechanism of C activation and the opsonization vs. long circulation (stealth) paradox. In reviewing the methods of assessing C activation and CARPA, we delineate the most sensitive porcine model and an algorithm for stepwise evaluation of the CARPA risk of i.v. liposomes, which are proposed for standardization for preclinical toxicology evaluation of liposomal and other nanoparticulate drug candidates. - Highlights: • Outlining of difficulties in generic development of liposomal drugs. • New regulatory requirements to evaluate CARPA in preclinical studies. • Review of complement activation by liposomes and its adverse consequences (CARPA). • Assays of C activation in vitro and CARPA in vivo, with the porcine test in focus. • Decision tree how to handle the risk of CARPA assessed by a battery of tests.

  5. Development of Liposomal Ciprofloxacin to Treat Lung Infections

    Directory of Open Access Journals (Sweden)

    David Cipolla

    2016-03-01

    Full Text Available Except for management of Pseudomonas aeruginosa (PA in cystic fibrosis, there are no approved inhaled antibiotic treatments for any other diseases or for infections from other pathogenic microorganisms such as tuberculosis, non-tuberculous mycobacteria, fungal infections or potential inhaled biowarfare agents including Francisella tularensis, Yersinia pestis and Coxiella burnetii (which cause pneumonic tularemia, plague and Q fever, respectively. Delivery of an antibiotic formulation via the inhalation route has the potential to provide high concentrations at the site of infection with reduced systemic exposure to limit side effects. A liposomal formulation may improve tolerability, increase compliance by reducing the dosing frequency, and enhance penetration of biofilms and treatment of intracellular infections. Two liposomal ciprofloxacin formulations (Lipoquin® and Pulmaquin® that are in development by Aradigm Corporation are described here.

  6. Preparation, characterization, and in vitro release study of albendazole-encapsulated nanosize liposomes

    Science.gov (United States)

    Panwar, Preety; Pandey, Bhumika; Lakhera, P C; Singh, K P

    2010-01-01

    The purpose of the present study was to formulate effective and controlled release albendazole liposomal formulations. Albendazole, a hydrophobic drug used for the treatment of hydatid cysts, was encapsulated in nanosize liposomes. Rapid evaporation method was used for the preparation of albendazole-encapsulated conventional and PEGylated liposomes consisting of egg phosphatidylcholine (PC) and cholesterol (CH) in the molar ratios of (6:4) and PC:CH: polyethylene glycol (PEG) (5:4:1), respectively. In this study, PEGylated and conventional liposomes containing albendazole were prepared and their characteristics, such as particle size, encapsulation efficiency, and in vitro drug release were investigated. The drug encapsulation efficiency of PEGylated and conventional liposomes was 81% and 72%, respectively. The biophysical characterization of both conventional and PEG-coated liposomes were done by transmission electron microscopy and UV-vis spectrophotometry. Efforts were made to study in vitro release of albendazole. The drug release rate showed decrease in albendazole release in descending order: free albendazole, albendazole-loaded conventional liposomes, and least with albendazole-loaded PEG-liposomes. Biologically relevant vesicles were prepared and in vitro release of liposome-entrapped albendazole was determined. PMID:20309396

  7. Analysis of a multicomponent gas absorption system with carrier gas coabsorption

    International Nuclear Information System (INIS)

    Merriman, J.R.

    1975-03-01

    Conventional integrated versions of the packed gas absorber design equations do not account for significant coabsorption of the carrier gas along with the dilute transferring species. These equations, as a result, also neglect the relationship between dilute component transfer and carrier gas coabsorption. In the absorption of Kr and Xe from various carrier gases, using CCl 2 F 2 as the process solvent, carrier coabsorption is substantial. Consequently, a design package was developed to deal with multicomponent gas absorption in systems characterized by carrier gas coabsorption. Developed within the general film theory framework, the basic feature of this design approach is a view of dilute component mass-transfer as a conventional diffusive transfer superimposed on a net flux caused by carrier absorption. Other supporting elements of the design package include predictive techniques for various fluid properties, estimating procedures for carrier gas equilibrium constants, and correlations for carrier gas and dilute gas mass-transfer coefficients. When applied to systems using CCl 2 F 2 as the solvent; He, N 2 , air, or Ar as the carrier gas; and Kr or Xe as the dilute gas; the design approach gave good results, even when extended to conditions well beyond those of its development. (U.S.)

  8. Treatment of deep mycoses with liposomal amphotericin B.

    Science.gov (United States)

    Berenguer, J; Muñoz, P; Parras, F; Fernández-Baca, V; Hernández-Sampelayo, T; Bouza, E

    1994-06-01

    Amphotericin B is the mainstay of therapy of many deep mycoses, but its use is seriously hampered by dose-limiting nephrotoxicity. In this study a liposomal formulation of amphotericin B was administered to ten patients with proven deep mycoses: invasive aspergillosis (n = 4), deep candidiasis (n = 4) and zygomycosis (n = 2). The mean daily dosage of liposomal amphotericin B was 3.0 mg/kg (range 2.5 to 4 mg/kg), the mean total dosage of liposomal amphotericin B 2,781 mg (range 87 to 5,220 mg) and the mean duration of treatment 17 days (range 3 to 33 days). Treatment with liposomal amphotericin B was associated with little nephrotoxicity and an overall survival rate of 50%. The median increase of serum creatinine from baseline levels was 0.38 mg/dl (-1.2 to 2.6 mg/dl).

  9. Multimodality imaging demonstrates trafficking of liposomes preferentially to ischemic myocardium

    International Nuclear Information System (INIS)

    Lipinski, Michael J.; Albelda, M. Teresa; Frias, Juan C.; Anderson, Stasia A.; Luger, Dror; Westman, Peter C.; Escarcega, Ricardo O.; Hellinga, David G.; Waksman, Ron; Arai, Andrew E.; Epstein, Stephen E.

    2016-01-01

    Introduction: Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia–reperfusion murine myocardial infarction model. Methods: Mice underwent ischemia–reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24 h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging. Results: The mean size of the liposomes was 100 nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163 ± 31% vs. 13 ± 14%, p = 0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium. Conclusions: Liposomes traffic to the heart and preferentially home to regions of myocardial injury, enabling improved diagnosis of myocardial injury and could serve as a vehicle for drug delivery.

  10. Multimodality imaging demonstrates trafficking of liposomes preferentially to ischemic myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Lipinski, Michael J., E-mail: mjlipinski12@gmail.com [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States); Albelda, M. Teresa [GIBI2" 3" 0, Grupo de Investigación Biomédica en Imagen, IIS La Fe, Valencia (Spain); Frias, Juan C. [Departamento de Ciencias Biomédicas, Universidad CEU Cardenal Herrera, Valencia (Spain); Anderson, Stasia A. [Advanced Cardiovascular Imaging Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (United States); Luger, Dror; Westman, Peter C.; Escarcega, Ricardo O.; Hellinga, David G.; Waksman, Ron [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States); Arai, Andrew E. [Advanced Cardiovascular Imaging Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (United States); Epstein, Stephen E. [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States)

    2016-03-15

    Introduction: Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia–reperfusion murine myocardial infarction model. Methods: Mice underwent ischemia–reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24 h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging. Results: The mean size of the liposomes was 100 nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163 ± 31% vs. 13 ± 14%, p = 0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium. Conclusions: Liposomes traffic to the heart and preferentially home to regions of myocardial injury, enabling improved diagnosis of myocardial injury and could serve as a vehicle for drug delivery.

  11. Liposome-mediated amplified detection of cell-secreted matrix metalloproteinase-9†

    Science.gov (United States)

    Banerjee, Jayati; Hanson, Andrea J.; Nyren-Erickson, Erin K.; Ganguli, Bratati; Wagh, Anil; Muhonen, Wallace W.; Law, Benedict; Shabb, John B.; Srivastava, D. K.; Mallik, Sanku

    2018-01-01

    A liposome-based amplified detection system is presented for the cancer cell secreted pathogenic enzyme matrix metalloproteinase-9 which does not require the use of biological antibodies. PMID:20424776

  12. Integration of β-carotene molecules in small liposomes

    International Nuclear Information System (INIS)

    Andreeva, Atanaska; Popova, Antoaneta

    2010-01-01

    The most typical feature of carotenoids is the long polyene chain with conjugated double bonds suggesting that they can serve as conductors of electrons, acting as 'molecular wires', important elements in the molecular electronic devices. Carotenoids are essential components of photosynthetic systems, performing different functions as light harvesting, photoprotection and electron transfer. They act also as natural antioxidants. In addition they perform structural role stabilizing the three-dimensional organization of photosynthetic membranes. Carotenoids contribute to the stability of the lipid phase, preserving the membrane integrity under potentially harmful environmental conditions. Carotenoids can be easily integrated into model membranes, facilitating the investigation of their functional roles. In carotenoid-egg phosphatidylcholine (EPC) liposomes ss-carotene is randomly distributed in the hydrocarbon interior of the bilayer, without any preferred, well defined orientation and retains a substantial degree of mobility. Here we investigate the degree of integration of ss-carotene in small unilamellar EPC liposomes and the changes in ss-carotene absorption and Raman spectra due to the lipid-pigment interaction. All observed changes in ss-carotene absorption and Raman spectra may be regarded as a result of the lipid-pigment interactions leading to the polyene geometry distortion and increasing of the environment heterogenety in the liposomes as compared to the solutions.

  13. In vitro and in vivo studies of gadolinium-159 liposomes in cancer treatment

    International Nuclear Information System (INIS)

    Soares, Daniel Cristian Ferreira

    2011-01-01

    In Brazil, estimates of new cancer cases, valid for the years 2010 and 2011 show that the disease will be responsible for the deaths of about 500,000 people. As an alternative therapy the radiotherapy technique, widely used in treating various types of tumors, act indiscriminate tumoral and healthy cells. Seeking to minimize these effects, nano structured carriers containing radioisotopes, such as liposomes, have been studied with the aim of improving the specificity of action of ionizing radiation, delivering and retaining adequate amounts of radioactive material in tumor cells, leading them to death. In this context, the present study, we prepared liposomes stealth pH-sensitive metal complex containing the radioactive 159 Gd-DTPA-BMA ( 159 Gd-SpHL) aiming to study in vitro and in vivo its effects in cancer treatment. The vesicles showed encapsulation rate of about 20%, average diameter of 100 nm and low release kinetics of radioactivity in biological media. The formulation was characterized through physic-chemical and morphological studies and the results revealed a low polydispersity index and negative Zeta potential. We studied in vitro and in vivo its action against the cells of Ehrlich tumor models and RT2 (rat glioma). The results of in vitro studies showed that the complex has significant radioactive cytotoxicity against the cells of two of the three models studied and that, being encapsulated in liposomes, the cytotoxicity was greatly enhanced. Additionally, we investigated the involvement of caspase-3 protein in Ehrlich and RT2 cell death. The results suggest that the main mechanism involved in the cytotoxic action of radioactive complex is related to apoptosis. The results of in vivo studies showed that liposomes containing 159 Gd-DTPA-BMA accumulated significantly in Ehrlich solid tumor in mice. Aiming to improve this uptake, we prepared pH-sensitive liposomes coated with folate containing the same radioactive complex ( 159 Gd-FTSpHL). The results

  14. Fluorescence Resonance Energy Transfer in Polydiacetylene Liposomes

    Science.gov (United States)

    Li, Xuelian; Matthews, Shelton; Kohli, Punit

    2009-01-01

    Conjugated polydiacetylene (PDA) possessing stimuli-responsive properties has been intensively investigated for developing efficient sensors. We report here fluorescence resonance energy transfer (FRET) in liposomes synthesized using different molar ratios of dansyl-tagged diacetylene and diacetylene–carboxylic acid monomers. Photopolymerization of diacetylene resulted in cross-linked PDA liposomes. We used steady-state electronic absorption, emission, and fluorescence anisotropy (FA) analysis to characterize the thermal-induced FRET between dansyl fluorophores (donor) and PDA (acceptor). We found that the monomer ratio of acceptor to donor (Rad) and length of linkers (functional part that connects dansyl fluorophores to the diacetylene group in the monomer) strongly affected FRET. For Rad = 10 000, the acceptor emission intensity was amplified by more than 18 times when the liposome solution was heated from 298 to 338 K. A decrease in Rad resulted in diminished acceptor emission amplification. This was primarily attributed to lower FRET efficiency between donors and acceptors and a higher background signal. We also found that the FRET amplification of PDA emissions after heating the solution was much higher when dansyl was linked to diacetylene through longer and flexible linkers than through shorter linkers. We attributed this to insertion of dansyl in the bilayer of the liposomes, which led to an increased dansyl quantum yield and a higher interaction of multiple acceptors with limited available donors. This was not the case for shorter and more rigid linkers where PDA amplification was much smaller. The present studies aim at enhancing our understanding of FRET between fluorophores and PDA-based conjugated liposomes. Furthermore, receptor tagged onto PDA liposomes can interact with ligands present on proteins, enzymes, and cells, which will produce emission sensing signal. Therefore, using the present approach, there exist opportunities for designing FRET

  15. The use of asymmetrical flow field-flow fractionation with on-line detection in the study of drug retention within liposomal nanocarriers and drug transfer kinetics.

    Science.gov (United States)

    Hinna, Askell Hvid; Hupfeld, Stefan; Kuntsche, Judith; Brandl, Martin

    2016-05-30

    approximately 300 min. As expected, equilibrium distribution between donor- and acceptor vesicles was proportional to the lipid mass ratio. An initial rapid transfer of p-THPP was found (∼ 5%) and investigated further by determining the extent of transfer between donor and acceptor during separation. The donor- and acceptor phase were found to be separated within few minutes and only minor (≤ 2%) transfer could be detected within the AF4 channel under the conditions applied for fractionation. These results demonstrates the potential of our AF4 based method as an in vitro tool to determine retention properties of lipophilic compounds within liposomal carriers in particular, but also within a variety of nano-particulate carriers provided that they exhibit a sufficient size difference compared to the applied colloidal acceptor phase. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Comparison of BCG, MPL and cationic liposome adjuvant systems in leishmanial antigen vaccine formulations against murine visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Bhowmick Sudipta

    2010-06-01

    Full Text Available Abstract Background The development of an effective vaccine against visceral leishmaniasis (VL caused by Leishmania donovani is an essential aim for controlling the disease. Use of the right adjuvant is of fundamental importance in vaccine formulations for generation of effective cell-mediated immune response. Earlier we reported the protective efficacy of cationic liposome-associated L. donovani promastigote antigens (LAg against experimental VL. The aim of the present study was to compare the effectiveness of two very promising adjuvants, Bacille Calmette-Guerin (BCG and Monophosphoryl lipid A (MPL plus trehalose dicorynomycolate (TDM with cationic liposomes, in combination with LAg, to confer protection against murine VL. Results All the three formulations afforded significant protection against L. donovani in both the visceral organs, liver and spleen. Although comparable level of protection was observed in BCG+LAg and MPL-TDM+LAg immunized mice, highest level of protection was exhibited by the liposomal LAg immunized group. Significant increase in anti-LAg IgG levels were detected in both MPL-TDM+LAg and liposomal LAg immunized animals with higher levels of IgG2a than IgG1. But BCG+LAg failed to induce any antibody response. As an index of cell-mediated immunity DTH responses were measured and significant response was observed in mice vaccinated with all the three different formulations. However, highest responses were observed with liposomal vaccine immunization. Comparative evaluation of IFN-γ and IL-4 responses in immunized mice revealed that MPL-TDM+LAg group produced the highest level of IFN-γ but lowest IL-4 level, while BCG+LAg demonstrated generation of suboptimum levels of both IFN-γ and IL-4 response. Elicitation of moderate levels of prechallenge IFN-γ along with optimum IL-4 corresponds with successful vaccination with liposomal LAg. Conclusion This comparative study reveals greater effectiveness of the liposomal vaccine for

  17. Placing and shaping liposomes with reconfigurable DNA nanocages

    Science.gov (United States)

    Zhang, Zhao; Yang, Yang; Pincet, Frederic; C. Llaguno, Marc; Lin, Chenxiang

    2017-07-01

    The diverse structure and regulated deformation of lipid bilayer membranes are among a cell's most fascinating features. Artificial membrane-bound vesicles, known as liposomes, are versatile tools for modelling biological membranes and delivering foreign objects to cells. To fully mimic the complexity of cell membranes and optimize the efficiency of delivery vesicles, controlling liposome shape (both statically and dynamically) is of utmost importance. Here we report the assembly, arrangement and remodelling of liposomes with designer geometry: all of which are exquisitely controlled by a set of modular, reconfigurable DNA nanocages. Tubular and toroid shapes, among others, are transcribed from DNA cages to liposomes with high fidelity, giving rise to membrane curvatures present in cells yet previously difficult to construct in vitro. Moreover, the conformational changes of DNA cages drive membrane fusion and bending with predictable outcomes, opening up opportunities for the systematic study of membrane mechanics.

  18. Liposomes derivatized with multimeric copies of KCCYSL peptide as targeting agents for HER-2-overexpressing tumor cells

    Directory of Open Access Journals (Sweden)

    Ringhieri P

    2017-01-01

    Full Text Available Paola Ringhieri,1 Silvia Mannucci,2 Giamaica Conti,2 Elena Nicolato,2 Giulio Fracasso,3 Pasquina Marzola,4 Giancarlo Morelli,1 Antonella Accardo1 1Department of Pharmacy and Interuniversity Research Centre on Bioactive Peptides (CIRPeB, University of Naples “Federico II”, Napoli, 2Department of Neurological Biomedical and Movement Sciences, 3Section of Immunology, Department of Medicine, 4Department of Informatics, University of Verona, Verona, Italy Abstract: Mixed liposomes, obtained by coaggregation of 1,2-dioleoyl-sn-glycero-3-phosphocholine and of the synthetic monomer containing a gadolinium complex ([C18]2DTPA[Gd] have been prepared. Liposomes externally decorated with KCCYSL (P6.1 peptide sequence in its monomeric, dimeric, and tetrameric forms are studied as target-selective delivery systems toward cancer cells overexpressing human epidermal growth factor receptor-2 (HER-2 receptors. Derivatization of liposomal surface with targeting peptides is achieved using the postmodification method: the alkyne-peptide derivative Pra-KCCYSL reacts, through click chemistry procedures, with a synthetic surfactant modified with 1, 2, or 4 azido moieties previously inserted in liposome formulation. Preliminary in vitro data on MDA-MB-231 and BT-474 cells indicated that liposomes functionalized with P6.1 peptide in its tetrameric form had better binding to and uptake into BT-474 cells compared to liposomes decorated with monomeric or dimeric versions of the P6.1 peptide. BT-474 cells treated with liposomes functionalized with the tetrameric form of P6.1 showed high degree of liposome uptake, which was comparable with the uptake of anti-HER-2 antibodies such as Herceptin. Moreover, magnetic MRI experiments have demonstrated the potential of liposomes to act as MRI contrast agents. Keywords: anti-HER2 liposomes, target peptide, KCCYSL peptide, breast cancer, click chemistry, branched peptides 

  19. Liposomes self-assembled from electrosprayed composite microparticles

    International Nuclear Information System (INIS)

    Yu Dengguang; Yang Junhe; Wang Xia; Tian Feng

    2012-01-01

    Composite microparticles, consisting of polyvinylpyrrolidone (PVP), naproxen (NAP) and lecithin (PC), have been successfully prepared using an electrospraying process and exploited as templates to manipulate molecular self-assembly for the synthesis of liposomes in situ. Field emission scanning electron microscope (FESEM) and transmission electron microscope (TEM) observations demonstrate that the microparticles have an average diameter of 960 ± 140 nm and a homogeneous structure. X-ray diffraction (XRD) patterns, differential scanning calorimetry (DSC) and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) results verify that the building blocks NAP and PC are scattered in the polymer matrix in a molecular way owing to the very fast drying of the electrospraying process and the favorable secondary interactions among the components. FESEM, scanning probe microscope (SPM) and TEM observations demonstrate that the liposomes can be achieved through molecular self-assembly in situ when the microparticles contact water thanks to ‘like prefers like’ and by means of the confinement effect of the microparticles. The liposomes have an encapsulation rate of 91.3%, and 80.7% of the drug in the liposomes can be freed into the dissolution medium in a sustained way and by a diffusion mechanism over a period of 24 h. The developed strategy not only provides a new, facile, and effective method to assemble and organize molecules of multiple components into liposomes with electrosprayed microparticles as templates, but also opens a new avenue for nanofabrication in a step-by-step and controllable way. (paper)

  20. Oral administration of insulin by means of liposomes in animal experiments

    International Nuclear Information System (INIS)

    Tragl, K.H.; Pohl, A.; Kinast, H.

    1979-01-01

    Liposomes are an effective vehicle for the oral administration of insulin. They are prepared from lipid emulsions by sonication and particles of homogeneous size are generated by elution through sepharose columns. Liposomes are taken up into the gastric mucosa by endocytosis and then transported to the liver via the portal circulation. Oral administration of 10 U insulin/kg body weight to rats is followed by a reduction in blood glucose to 67% of the initial value. When liposome-trapped insulin was injected intravenously a decrease in blood glucose to 40% of the initial value was obtained by the administration of 5 IU insulin/kg body weight. While the effect of orally-administered liposome-trapped insulin is obvious, the problems of standardization of the insulin content of the liposomes and the great variability of liposome uptake into the gastric mucosa by endocytosis remain unsolved. (author)

  1. Exchangeable pulmonary water space evaluation using giant liposomes

    International Nuclear Information System (INIS)

    Santos, A.C.; Ribeiro, M.J.; Ferreira, N.; De Lima, J.J.P.

    1998-01-01

    The present work aims to study the potential use of liposomes for the evaluation of pulmonary exchangeable water space, important parameter in some pulmonary oedema situations. This study is based upon the delivery of a diffusible water radiotracer into pulmonary capillary network, which equilibrates with interstitial water space of the lung and returns to the blood circulation. The time constant of this phenomena depends on the magnitude of the water space under study. The release of the diffusible radiotracer in lung capillaries is performed using liposomes with specific formulation. The giant liposomes (15-30μm diameter) used in this study are instable at 37 deg. C. They are biocompatible, biodegradable, with low toxicity and showed no immunogenicity. A water tracer labelled with 99m Tc, encapsulated in the aqueous phase of giant liposomes, has been used. Liposomes were prepared in sterile conditions and with apyrogenic materials. The lipid films composition is L-α-diestearoylphosphatidylcholine (DSPC), L-α-phosphatidyl-DL-glycerol (EPG) and cholesterol (CHOL) (60%/10%/30% mass ratio). After iv injection at +-20 deg. C in the femoral vein of Wistar rats (300g-600g) or albine rabbits (4.5-5Kg), the thermolabile liposomes will be entrapped in lung capillaries and release the radiotracer locally. When the radiodrug is diffusible we will evaluate the volume of the exchangeable pulmonary water analyzing the activity/time curves. These curves are slower for greater water spaces. When the radiotracer is non-diffusible, the disappearance curves are not influenced by the extravascular water space. (author)

  2. Encapsulating contact allergens in liposomes, ethosomes, and polycaprolactone may affect their sensitizing properties

    DEFF Research Database (Denmark)

    Madsen, Jakob Torp; Vogel, Stefan; Johansen, Jeanne Duus

    2011-01-01

    Attempts to improve formulation of topical products are a continuing process and the development of micro- and nanovesicular systems as well as polymeric microparticles has led to marketing of topical drugs and cosmetics using these technologies. Encapsulation of some well-known contact allergens...... in ethanolic liposomes have been reported to enhance allergenicity compared with the allergens in similar vehicles without liposomes. The present report includes data on more sensitization studies using the mouse local lymph node assay with three contact allergens encapsulated in different dermal drug...... dichromate compared with control solutions. However, encapsulating the lipophilic contact allergen dinitrochlorobenzene (DNCB) in polycaprolactone reduced the sensitizing capacity to 1211 ± 449 compared with liposomes (7602 ± 2658) and in acetone:olive oil (4:1) (5633 ± 666). The same trend was observed...

  3. Effect of Lipid Composition on In Vitro Release and Skin Deposition of Curcumin Encapsulated Liposomes

    Directory of Open Access Journals (Sweden)

    Geethi Pamunuwa

    2016-01-01

    Full Text Available Liposomal encapsulation improves numerous physiochemical and biological properties of curcumin. The aim of this work was to impart slow release and skin delivery of curcumin via liposomal encapsulation. Liposomes were made using egg yolk phosphatidylcholine as the staple lipid while incorporating polysorbate 80 and stearylamine to prepare hybrid liposomes and positively charged liposomes, respectively. Negatively charged liposomes exhibited the highest encapsulation efficiencies (87.8±4.3% and loading capacities (3.4±0.2%. The sizes of all formulations were about 250 nm, while stearylamine increased the polydispersity index. Positively charged liposomes showed lower degradation temperatures than negatively charged liposomes by 10–15°C, attributable to the presence of stearylamine. The melting temperatures of positively charged liposomes (40–50°C were much higher than those of negatively charged liposomes (14-15°C, which may have affected release and skin deposition behavior of liposomes. The positively charged liposomes exhibited the slowest release of curcumin in phosphate buffered saline (pH 6.8 and the release profiles of all liposomal formulations conformed to the Gompertz model. The negatively charged liposomes facilitated the highest skin deposition of curcumin as revealed by studies conducted using excised pig ear skin. Concisely, positively and negatively charged liposomes were optimal for slow release and skin deposition of curcumin, respectively.

  4. Atomic Force Microscopy Study on the Stiffness of Nanosized Liposomes Containing Charged Lipids.

    Science.gov (United States)

    Takechi-Haraya, Yuki; Goda, Yukihiro; Sakai-Kato, Kumiko

    2018-06-18

    It has recently been recognized that the mechanical properties of lipid nanoparticles play an important role during in vitro and in vivo behaviors such as cellular uptake, blood circulation, and biodistribution. However, there have been no quantitative investigations of the effect of commonly used charged lipids on the stiffness of nanosized liposomes. In this study, by means of atomic force microscopy (AFM), we quantified the stiffness of nanosized liposomes composed of neutrally charged lipids combined with positively or negatively charged lipids while simultaneously imaging the liposomes in aqueous medium. Our results showed that charged lipids, whether negatively or positively charged, have the effect of reducing the stiffness of nanosized liposomes, independently of the saturation degree of the lipid acyl chains; the measured stiffness values of liposomes containing charged lipids are 30-60% lower than those of their neutral counterpart liposomes. In addition, we demonstrated that the Laurdan generalized polarization values, which are related to the hydration degree of the liposomal membrane interface and often used as a qualitative indicator of liposomal membrane stiffness, do not directly correlate with the physical stiffness values of the liposomes prepared in this study. However, our results indicate that direct quantitative AFM measurement is a valuable method to gain molecular-scale information about how the hydration degree of liposomal interfaces reflects (or does not reflect) liposome stiffness as a macroscopic property. Our AFM method will contribute to the quantitative characterization of the nano-bio interaction of nanoparticles and to the optimization of the lipid composition of liposomes for clinical use.

  5. Poly(amino acid)s: next-generation coatings for long-circulating liposomes

    NARCIS (Netherlands)

    Romberg, B.

    2007-01-01

    Incorporation of a lipid conjugate of a water-soluble polymer into liposomes can reduce the adhesion of plasma proteins that would otherwise cause rapid recognition and removal of the liposomes by phagocytes. Such polymer-coated liposomes show prolonged circulation property and passive targeting to

  6. Study of the Dynamic Uptake of Free Drug and Nanostructures for Drug Delivery Based on Bioluminescence Measurements

    Directory of Open Access Journals (Sweden)

    Zhongjian Fang

    2017-01-01

    Full Text Available The past two decades have witnessed the great growth of the development of novel drug carriers. However, the releasing dynamics of drug from drug carriers in vivo and the interactions between cells and drug carriers remain unclear. In this paper, liposomes were prepared to encapsulate D-luciferin, which was the substrate of luciferase and served as a model drug. Based on the theoretical calculation of active loading, methods of preparation for liposomes were optimized. Only when D-luciferin was released from liposomes or taken in by the cells could bioluminescence be produced under the catalysis of luciferase. Models of multicellular tumor spheroid (MCTS were built with 4T1-luc cells that expressed luciferase stably. The kinetic processes of uptake and distribution of free drugs and liposomal drugs were determined with models of cell suspension, monolayer cells, MCTS, and tumor-bearing nude mice. The technology platform has been demonstrated to be effective for the study of the distribution and kinetic profiles of various liposomes as drug delivery systems.

  7. FUNCTIONALIZATION OF 3D FIBROUS SCAFFOLDS PREPARED USING CENTRIFUGAL SPINNING WITH LIPOSOMES AS A SIMPLE DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Michala Rampichová

    2017-06-01

    Full Text Available 3D materials supporting cell adhesion, infiltration and proliferation are crucial for bone tissue engineering. In the current study we combined PCL fibers prepared using centrifugal spinning with adhered liposomes filled with platelet lysate as a natural source of growth factors. The scaffold was seeded with MG-63 cells and tested in vitro as a potential drug delivery system for bone tissue engineering.

  8. Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review

    Science.gov (United States)

    Riaz, Muhammad Kashif; Riaz, Muhammad Adil; Zhang, Xue; Lin, Congcong; Wong, Ka Hong; Chen, Xiaoyu; Lu, Aiping

    2018-01-01

    Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes) containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed. PMID:29315231

  9. Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review

    Directory of Open Access Journals (Sweden)

    Muhammad Kashif Riaz

    2018-01-01

    Full Text Available Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed.

  10. Bioreactor droplets from liposome-stabilized all-aqueous emulsions

    Science.gov (United States)

    Dewey, Daniel C.; Strulson, Christopher A.; Cacace, David N.; Bevilacqua, Philip C.; Keating, Christine D.

    2014-08-01

    Artificial bioreactors are desirable for in vitro biochemical studies and as protocells. A key challenge is maintaining a favourable internal environment while allowing substrate entry and product departure. We show that semipermeable, size-controlled bioreactors with aqueous, macromolecularly crowded interiors can be assembled by liposome stabilization of an all-aqueous emulsion. Dextran-rich aqueous droplets are dispersed in a continuous polyethylene glycol (PEG)-rich aqueous phase, with coalescence inhibited by adsorbed ~130-nm diameter liposomes. Fluorescence recovery after photobleaching and dynamic light scattering data indicate that the liposomes, which are PEGylated and negatively charged, remain intact at the interface for extended time. Inter-droplet repulsion provides electrostatic stabilization of the emulsion, with droplet coalescence prevented even for submonolayer interfacial coatings. RNA and DNA can enter and exit aqueous droplets by diffusion, with final concentrations dictated by partitioning. The capacity to serve as microscale bioreactors is established by demonstrating a ribozyme cleavage reaction within the liposome-coated droplets.

  11. Multimodal targeted high relaxivity thermosensitive liposome for in vivo imaging

    Science.gov (United States)

    Kuijten, Maayke M. P.; Hannah Degeling, M.; Chen, John W.; Wojtkiewicz, Gregory; Waterman, Peter; Weissleder, Ralph; Azzi, Jamil; Nicolay, Klaas; Tannous, Bakhos A.

    2015-11-01

    Liposomes are spherical, self-closed structures formed by lipid bilayers that can encapsulate drugs and/or imaging agents in their hydrophilic core or within their membrane moiety, making them suitable delivery vehicles. We have synthesized a new liposome containing gadolinium-DOTA lipid bilayer, as a targeting multimodal molecular imaging agent for magnetic resonance and optical imaging. We showed that this liposome has a much higher molar relaxivities r1 and r2 compared to a more conventional liposome containing gadolinium-DTPA-BSA lipid. By incorporating both gadolinium and rhodamine in the lipid bilayer as well as biotin on its surface, we used this agent for multimodal imaging and targeting of tumors through the strong biotin-streptavidin interaction. Since this new liposome is thermosensitive, it can be used for ultrasound-mediated drug delivery at specific sites, such as tumors, and can be guided by magnetic resonance imaging.

  12. 6-mercaptopurine and daunorubicin double drug liposomes-preparation, drug-drug interaction and characterization.

    Science.gov (United States)

    Agrawal, Vineet; Paul, Manash K; Mukhopadhyay, Anup K

    2005-01-01

    This article addresses and investigates the dual incorporation of daunorubicin (DR) and 6-mercaptopurine (6-MP) in liposomes for better chemotherapy. These drugs are potential candidates for interaction due to the quinone (H acceptor) and hydroxyl (H donor) groups on DR and 6-MP, respectively. Interactions between the two drugs in solution were monitored by UV/Vis and fluorescence spectroscopy. Interaction between the two drugs inside the liposomes was evaluated by HPLC (for 6-MP) and by fluorescence spectroscopy (for daunorubicin) after phospholipase-mediated liposome lysis. Our results provide evidence for the lack of interaction between the two drugs in solution and in liposomes. The entrapment efficiencies of 6-MP in the neutral Phosphatidyl choline (PC):Cholesterol (Chol):: 2:1 and anionic PC:Chol:Cardiolipin (CL) :: 4:5:1 single and double drug liposomes were found to be 0.4% and 1.5% (on average), respectively. The entrapment efficiencies of DR in the neutral and anionic double drug liposomes were found to be 55% and 31%, respectively. The corresponding entrapment of daunorubicin in the single drug liposomes was found to be 62% on average. Our thin layer chromatography (TLC) and transmission electron microscopy (TEM) results suggest stability of lipid and liposomes, thus pointing plausible existence of double drug liposomes. Cytotoxicity experiments were performed by using both single drug and double drug liposomes. By comparing the results of phase contrast and fluorescence microscopy, it was observed that the double drug liposomes were internalized in the jurkat and Hut78 (highly resistant cell line) leukemia cells as viewed by the fluorescence of daunorubicin. The cytotoxicity was dose dependent and had shown a synergistic effect when double drug liposome was used.

  13. Influence of polymer size, liposomal composition, surface charge, and temperature on the permeability of pH-sensitive liposomes containing lipid-anchored poly(2-ethylacrylic acid

    Directory of Open Access Journals (Sweden)

    Lu T

    2012-09-01

    Full Text Available Tingli Lu,1 Zhao Wang,2 Yufan Ma,1 Yang Zhang,2 Tao Chen1,21Key Laboratory for Space Bioscience and Biotechnology, School of Life Science, Northwestern Polytechnical University, 2Liposome Research Centre, Xi'an, ChinaBackground: Liposomes containing pH-sensitive polymers are promising candidates for the treatment of tumors and localized infection. This study aimed to identify parameters influencing the extent of contents release from poly(ethylacrylic acid (PEAA vesicles, focusing on the effects of polymer size, lipid composition, vesicle surface charge, and temperature.Methods: Anchored lipid pH-sensitive PEAA was synthesized using PEAA with a molecular weight of 8.4 kDa. PEAA vesicles were prepared by insertion of the lipid-anchored PEAA into preformed large unilamellar vesicles. The preformed liposomes were manipulated by varying the phosphocholine and cholesterol content, and by adding negative or positive charges to the liposomes. A calcein release assay was used to evaluate the effects of polymer size, liposome composition, surface charge, and temperature on liposomal permeability.Results: The release efficiency of the calcein-entrapped vesicles was found to be dependent on the PEAA polymer size. PEAA vesicles containing a phosphatidylcholine to cholesterol ratio of 60:40 (mol/mol released more than 80% of their calcein content when the molecular weight of PEAA was larger than 8.4 kDa. Therefore, the same-sized polymer of 8.4 kDa was used for the rest of study. The calcein release potential was found to decrease as the percentage of cholesterol increased and with an increase in the phosphocholine acyl chain length (DMPC . DPPC . DSPC. Negatively charged and neutral vesicles released similar amounts of calcein, whereas positively charged liposomes released a significant amount of their contents. pH-sensitive release was dependent on temperature. Dramatic content release was observed at higher temperatures.Conclusion: The observed

  14. Liposomes: structure, properties and methods of curative administration in organism

    Directory of Open Access Journals (Sweden)

    M. A. Kisyakova

    2010-07-01

    Full Text Available A review of data from scientific sources, devoted to problems of liposomes’ structure, properties and processes of formation was made. Advantages of liposomes used for medical purposes are shown. Methods of liposomes administration in an organism are characterised. Data on mechanisms of interaction between liposomes and cells, peculiarities of liposomes’ lipids composition and dependence of its tropism to definite organs and tissues are generalised.

  15. Effect of liposomes on rheological and syringeability properties of hyaluronic acid hydrogels intended for local injection of drugs.

    Science.gov (United States)

    El Kechai, Naila; Bochot, Amélie; Huang, Nicolas; Nguyen, Yann; Ferrary, Evelyne; Agnely, Florence

    2015-06-20

    The aim of this work was to thoroughly study the effect of liposomes on the rheological and the syringeability properties of hyaluronic acid (HA) hydrogels intended for the local administration of drugs by injection. Whatever the characteristics of the liposomes added (neutral, positively or negatively charged, with a corona of polyethylene glycol chains, size), the viscosity and the elasticity of HA gels increased in a lipid concentration-dependent manner. Indeed, liposomes strengthened the network formed by HA chains due to their interactions with this polymer. The nature and the resulting effects of these interactions depended on liposome composition and concentration. The highest viscosity and elasticity were observed with liposomes covered by polyethylene glycol chains while neutral liposomes displayed the lowest effect. Despite their high viscosity at rest, all the formulations remained easily injectable through needles commonly used for local injections thanks to the shear-thinning behavior of HA gels. The present study demonstrates that rheological and syringeability tests are both necessary to elucidate the behavior of such systems during and post injection. In conclusion, HA liposomal gels appear to be a promising and versatile formulation platform for a wide range of applications in local drug delivery when an injection is required. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. An evaluation of anti-tumor effect and toxicity of PEGylated ursolic acid liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qianqian; Zhao, Tingting; Liu, Yanping; Xing, Shanshan; Li, Lei; Gao, Dawei, E-mail: dwgao@ysu.edu.cn [Yanshan University, Applying Chemistry Key Lab of Hebei Province, Department of Bioengineer (China)

    2016-02-15

    Therapy of solid tumors mediated by nano-drug delivery has attracted considerable interest. In our previous study, ursolic acid (UA) was successfully encapsulated into PEGylated liposomes. The study aimed to evaluate the tumor inhibition effect and cytotoxicity of the PEGylated UA liposomes by U14 cervical carcinoma-bearing mice. The liposomes were spherical particles with mean particle diameters of 127.2 nm. The tumor inhibition rate of PEGylated UA liposomes was 53.60 % on U14 cervical carcinoma-bearing mice, which was greater than those of the UA solution (18.25 %) and traditional UA liposome groups (40.75 %). The tumor cells apoptosis rate of PEGylated UA liposomes was 25.81 %, which was significantly higher than that of the traditional UA liposomes (13.37 %). Moreover, the kidney and liver did not emerge the pathological changes in UA therapeutic mice by histopathological analysis, while there were significant differences on tumor tissues among three UA formulation groups. The PEGylated UA liposomes exhibited higher anti-tumor activity and lower cytotoxicity, and the main reason was that the coating PEG layer improved UA liposome properties, such as enhancing the stability of liposomes, promoting the effect of slow release, and prolonging the time of blood circulation. This may shed light on the development of PEGylated nano-vehicles.

  17. Estudos sobre liberação controlada e vetorização de drogas através de lipossomas

    OpenAIRE

    Gomes de Oliveira, Anselmo [UNESP; Cardillo, José Augusto; Scarpa, Maria Virgínia [UNESP; Wanczinski, Bruna Juliana [UNESP; Da Silva Jr., Arnóbio Antônio [UNESP

    2005-01-01

    The text highlights the state of research related with the application of liposomes in the control of drug delivery and drug target to infectious diseases. Liposomes have several pharmaceutical applications and this manuscript is primarily focused on the potential of this colloidal system as an antibiotic carrier system and of administration through several accesses via to organism. Numerous case studies in which liposomes have successfully been used to improve pharmacological drug effect are...

  18. Application of Pharmacokinetics Modelling to Predict Human Exposure of a Cationic Liposomal Subunit Antigen Vaccine System

    Directory of Open Access Journals (Sweden)

    Raj K. S. Badhan

    2017-12-01

    Full Text Available The pharmacokinetics of a liposomal subunit antigen vaccine system composed of the cationic lipid dimethyldioctadecylammonium bromide (DDA and the immunostimulatory agent trehalose 6,6-dibehenate (TDB (8:1 molar ratio combined with the Ag85B-ESAT-6 (H1 antigen were modelled using mouse in-vivo data. Compartment modelling and physiologically based pharmacokinetics (PBPK were used to predict the administration site (muscle and target site (lymph temporal concentration profiles and factors governing these. Initial estimates using compartmental modelling established that quadriceps pharmacokinetics for the liposome demonstrated a long half-life (22.6 days compared to the associated antigen (2.62 days. A mouse minimal-PBPK model was developed and successfully predicted quadriceps liposome and antigen pharmacokinetics. Predictions for the popliteal lymph node (PLN aligned well at earlier time-points. A local sensitivity analysis highlighted that the predicted AUCmuscle was sensitive to the antigen degradation constant kdeg (resulting in a 3-log change more so than the fraction escaping the quadriceps (fe (resulting in a 10-fold change, and the predicted AUCPLN was highly sensitive to fe. A global sensitivity analysis of the antigen in the muscle demonstrated that model predictions were within the 50th percentile for predictions and showed acceptable fits. To further translate in-vitro data previously generated by our group, the mouse minimal-PBPK model was extrapolated to humans and predictions made for antigen pharmacokinetics in muscle and PLN. Global analysis demonstrated that both kdeg and fe had a minimal impact on the resulting simulations in the muscle but a greater impact in the PLN. In summary, this study has predicted the in-vivo fate of DDA:TDB:H1 in humans and demonstrated the roles that formulation degradation and fraction escaping the depot site can play upon the overall depot effect within the site of administration.

  19. Nano carriers for drug transport across the blood-brain barrier.

    Science.gov (United States)

    Li, Xinming; Tsibouklis, John; Weng, Tingting; Zhang, Buning; Yin, Guoqiang; Feng, Guangzhu; Cui, Yingde; Savina, Irina N; Mikhalovska, Lyuba I; Sandeman, Susan R; Howel, Carol A; Mikhalovsky, Sergey V

    2017-01-01

    Effective therapy lies in achieving a therapeutic amount of drug to the proper site in the body and then maintaining the desired drug concentration for a sufficient time interval to be clinically effective for treatment. The blood-brain barrier (BBB) hinders most drugs from entering the central nervous system (CNS) from the blood stream, leading to the difficulty of delivering drugs to the brain via the circulatory system for the treatment, diagnosis and prevention of brain diseases. Several brain drug delivery approaches have been developed, such as intracerebral and intracerebroventricular administration, intranasal delivery and blood-to-brain delivery, as a result of transient BBB disruption induced by biological, chemical or physical stimuli such as zonula occludens toxin, mannitol, magnetic heating and ultrasound, but these approaches showed disadvantages of being dangerous, high cost and unsuitability for most brain diseases and drugs. The strategy of vector-mediated blood-to-brain delivery, which involves improving BBB permeability of the drug-carrier conjugate, can minimize side effects, such as being submicrometre objects that behave as a whole unit in terms of their transport and properties, nanomaterials, are promising carrier vehicles for direct drug transport across the intact BBB as a result of their potential to enter the brain capillary endothelial cells by means of normal endocytosis and transcytosis due to their small size, as well as their possibility of being functionalized with multiple copies of the drug molecule of interest. This review provids a concise discussion of nano carriers for drug transport across the intact BBB, various forms of nanomaterials including inorganic/solid lipid/polymeric nanoparticles, nanoemulsions, quantum dots, nanogels, liposomes, micelles, dendrimers, polymersomes and exosomes are critically evaluated, their mechanisms for drug transport across the BBB are reviewed, and the future directions of this area are fully

  20. Cytoprotective and enhanced anti-inflammatory activities of liposomal piroxicam formulation in lipopolysaccharide-stimulated RAW 264.7 macrophages

    Directory of Open Access Journals (Sweden)

    Chiong HS

    2013-03-01

    Full Text Available Hoe Siong Chiong,1 Yoke Keong Yong,1 Zuraini Ahmad,1 Mohd Roslan Sulaiman,1 Zainul Amiruddin Zakaria,1 Kah Hay Yuen,2 Muhammad Nazrul Hakim1,31Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia; 2School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor, Malaysia; 3Sports Academy, Universiti Putra Malaysia, Serdang, MalaysiaBackground: Liposomal drug delivery systems, a promising lipid-based nanoparticle technology, have been known to play significant roles in improving the safety and efficacy of an encapsulated drug.Methods: Liposomes, prepared using an optimized proliposome method, were used in the present work to encapsulate piroxicam, a widely prescribed nonsteroidal anti-inflammatory drug. The cytotoxic effects as well as the in vitro efficacy in regulation of inflammatory responses by free-form piroxicam and liposome-encapsulated piroxicam were evaluated using a lipopolysaccharide-sensitive macrophage cell line, RAW 264.7.Results: Cells treated with liposome-encapsulated piroxicam demonstrated higher cell viabilities than those treated with free-form piroxicam. In addition, the liposomal piroxicam formulation resulted in statistically stronger inhibition of pro-inflammatory mediators (ie, nitric oxide, tumor necrosis factor-α, interleukin-1β, and prostaglandin E2 than piroxicam at an equivalent dose. The liposome-encapsulated piroxicam also caused statistically significant production of interleukin-10, an anti-inflammatory cytokine.Conclusion: This study affirms the potential of a liposomal piroxicam formulation in reducing cytotoxicity and enhancing anti-inflammatory responses in vitro.Keywords: liposomes, nitric oxide, cytokines, prostaglandin E2, interleukin-1β, piroxicam

  1. Ultraviolet radiation-induced lipid peroxidation in liposomal membrane: modification by capsaicin

    International Nuclear Information System (INIS)

    De, A.K.; Ghosh, J.J.; Mandal, T.K.

    1993-01-01

    Ultraviolet-radiation has been reported to cause lipid peroxidation in the liposomal membrane. In the present study, treatment with capsaicin, (8-methyl-n-vanillyl-6-nonenamide), the pungent principle of red hot pepper, was shown to modify UV-induced lipid peroxidation in the liposomal membrane. Treatment with low doses of capsaicin (less than 0.1 μg/mL of phosphatidyl choline liposome) produced a significant increase in UV-induced lipid peroxidation, while high doses (0.1-0.5 μg/mL of PC liposome) caused a significant decrease of UV-induced peroxidation

  2. Ultraviolet radiation-induced lipid peroxidation in liposomal membrane: modification by capsaicin

    Energy Technology Data Exchange (ETDEWEB)

    De, A. K.; Ghosh, J. J.; Mandal, T. K. [University College of Science, Department of Biochemistry, 35 Ballygunge Circular Road, Calcutta 700-019 (India)

    1993-07-01

    Ultraviolet-radiation has been reported to cause lipid peroxidation in the liposomal membrane. In the present study, treatment with capsaicin, (8-methyl-n-vanillyl-6-nonenamide), the pungent principle of red hot pepper, was shown to modify UV-induced lipid peroxidation in the liposomal membrane. Treatment with low doses of capsaicin (less than 0.1 μg/mL of phosphatidyl choline liposome) produced a significant increase in UV-induced lipid peroxidation, while high doses (0.1-0.5 μg/mL of PC liposome) caused a significant decrease of UV-induced peroxidation.

  3. Nerve cell-mimicking liposomes as biosensor for botulinum neurotoxin complete physiological activity

    Energy Technology Data Exchange (ETDEWEB)

    Weingart, Oliver G., E-mail: Oliver.Weingart@hest.ethz.ch; Loessner, Martin J.

    2016-12-15

    Botulinum neurotoxins (BoNT) are the most toxic substances known, and their neurotoxic properties and paralysing effects are exploited for medical treatment of a wide spectrum of disorders. To accurately quantify the potency of a pharmaceutical BoNT preparation, its physiological key activities (binding to membrane receptor, translocation, and proteolytic degradation of SNARE proteins) need to be determined. To date, this was only possible using animal models, or, to a limited extent, cell-based assays. We here report a novel in vitro system for BoNT/B analysis, based on nerve-cell mimicking liposomes presenting motoneuronal membrane receptors required for BoNT binding. Following triggered membrane translocation of the toxin's Light Chain, the endopeptidase activity can be quantitatively monitored employing a FRET-based reporter assay within the functionalized liposomes. We were able to detect BoNT/B physiological activity at picomolar concentrations in short time, opening the possibility for future replacement of animal experimentation in pharmaceutical BoNT testing. - Highlights: • A cell-free in vitro system was used to measure BoNT/B physiological function. • The system relies on nerve-cell mimicking liposomes as a novel detection system. • A FRET-based reporter assay is used as final readout of the test system. • BoNT/B physiological activity was detected at picogram quantities in short time. • The method opens the possibility to replace animal experimentation in BoNT testing.

  4. Nerve cell-mimicking liposomes as biosensor for botulinum neurotoxin complete physiological activity

    International Nuclear Information System (INIS)

    Weingart, Oliver G.; Loessner, Martin J.

    2016-01-01

    Botulinum neurotoxins (BoNT) are the most toxic substances known, and their neurotoxic properties and paralysing effects are exploited for medical treatment of a wide spectrum of disorders. To accurately quantify the potency of a pharmaceutical BoNT preparation, its physiological key activities (binding to membrane receptor, translocation, and proteolytic degradation of SNARE proteins) need to be determined. To date, this was only possible using animal models, or, to a limited extent, cell-based assays. We here report a novel in vitro system for BoNT/B analysis, based on nerve-cell mimicking liposomes presenting motoneuronal membrane receptors required for BoNT binding. Following triggered membrane translocation of the toxin's Light Chain, the endopeptidase activity can be quantitatively monitored employing a FRET-based reporter assay within the functionalized liposomes. We were able to detect BoNT/B physiological activity at picomolar concentrations in short time, opening the possibility for future replacement of animal experimentation in pharmaceutical BoNT testing. - Highlights: • A cell-free in vitro system was used to measure BoNT/B physiological function. • The system relies on nerve-cell mimicking liposomes as a novel detection system. • A FRET-based reporter assay is used as final readout of the test system. • BoNT/B physiological activity was detected at picogram quantities in short time. • The method opens the possibility to replace animal experimentation in BoNT testing.

  5. Encapsulating contact allergens in liposomes, ethosomes, and polycaprolactone may affect their sensitizing properties

    DEFF Research Database (Denmark)

    Madsen, Jakob Torp; Vogel, Stefan; Johansen, Jeanne Duus

    2011-01-01

    Attempts to improve formulation of topical products are a continuing process and the development of micro- and nanovesicular systems as well as polymeric microparticles has led to marketing of topical drugs and cosmetics using these technologies. Encapsulation of some well-known contact allergens...... in ethanolic liposomes have been reported to enhance allergenicity compared with the allergens in similar vehicles without liposomes. The present report includes data on more sensitization studies using the mouse local lymph node assay with three contact allergens encapsulated in different dermal drug...... dichromate compared with control solutions. However, encapsulating the lipophilic contact allergen dinitrochlorobenzene (DNCB) in polycaprolactone reduced the sensitizing capacity to 1211 ± 449 compared with liposomes (7602 ± 2658) and in acetone:olive oil (4:1) (5633 ± 666). The same trend was observed...

  6. Evaluation of liposomes coated with a pH responsive polymer

    OpenAIRE

    Barea, M.J.; Jenkins, M.J.; Gaber, M.H.; Bridson, R.H.

    2010-01-01

    Liposomes have been coated with the pH responsive polymer, Eudragit S100, and the formulation's potential for lower gastrointestinal (GI) targeting following oral administration assessed. Cationic liposomes were coated with the anionic polymer through simple mixing. The evolution of a polymer coat was studied using zeta potential measurements and laser diffraction size analysis. Further evidence of an association between polymer and liposome was obtained using light and cryo scanning electron...

  7. Radioprotective effectiveness of Adeturone, incapsulated in liposomes

    International Nuclear Information System (INIS)

    Pantev, T.

    1990-01-01

    The radioprotective properties of Adeturone (S,2-aminoethyl isothiuronic adenosine-5-triphosphate), incapsulated in mono- and tricomponent lisosomes was studied. Intraperitoneal adminisration of the radioprotector by means of monocomponent liposomes from egg lecithins, as well as of the radioprotector alone shortly before (15-30 min) gamma irradiation of mice with 7.5 Gy (LD 100/30 ) provided high survival rate - accordingly 80% and 75%. Orally administered Adeturone incapsulated in tricomponent liposomes (dipalmitoil-DL-3-lecithin:cholesterine:stearilamine - 7:2:1) protected mice exposed to lethal X-irradiation (7.8 Gy, LD 90/30 ) for 0.5 to 4.5 hours. Adeturone, applied alone under these conditions 4.5 hours before irradiation, was ineffective. The results clearly demonstrated a prolonged radioprotective effect of Adeturone, administered per os as liposome suspension. 2 tabs., 17 refs

  8. Designing of 14C, 3H-labeled liposomal preparations and their distribution in inner organs of experimental animals

    International Nuclear Information System (INIS)

    Isaev, E.I.; Kamalova, M.E.; Isakova, A.V.; Mirakhmedov, F.K.; Saatov, T.S.

    2004-01-01

    Full text: Development of methods for introduction of drug liposomal forms into practice is an urgent task for medicine and radiobiology. Per oral way of administration of the medications has been unexplored properly yet. Preservation of their stability in the gastro-intestinal tract is the essential requirement to the liposomes. Literature data and our studies showed that the elevated saturation of fatty acids and viscosity of liposomal membrane bilayer increases their stability to acidic and alkaline media of the digestive system. To prepare the liposome we used 14C,H-labeled lipids isolated from tissues by means of preparative chromatography after administration of D(1-614C)glucose (specific radioactivity 100 mkCu/mM) as well as of D(1-3H)-galactose (specific radioactivity 900 mkCU/mM) to 10 rats. Organ-specific liposomes were prepared in accordance with the special method without ultrasound processing to administered them with milk per orally to rats by means of a gastric probe. Before administration of 14C,3H liposomes the animals were not fed for 16-20 hours for complete emptying of the gastrointestinal tract. Under these conditions 1-1.5 hours after administration of liposomes their maximum amount was absorbed from he intestine. We found tissue specificity of the liposome administered. If the amount of administered liposomes for each tissue to be taken for 100%, in target organs their distribution (in %) would be as follows: 0.30/0.39 in the heart, 0.54/0.06 in the skeletal muscle, 0.4/0.6 in the brain, 4.2/10.2 in the spleen, 2.9/6.1 in the pancreas, 5.1/1.2 in the kidney. In these experiments liposomes had covering of 14 C, 3 H-glycosphingolipids of the spleen. Under these conditions 3H-cAMP in the form of liposomes was administered to mice per orally to measure radioactivity (in cpm 100mg of tissue) in the organs. The values were as follows: 77±6.3 in the liver, 750±47 in the spleen, 250±19 in the kidney, 70±77 in the heart, 267±21 in the lung and 95

  9. Benchmarking of Sterilizing grade filters with liposome Filtration.

    Science.gov (United States)

    Loewe, Thomas; Mundlamuri, Ramesh; Loewe, Thomas; Mundrigi, Ashok; Handt, Sebastian; Singh, Bhuwan

    2017-12-14

    Cytotoxic drugs can be encapsulated in liposomes vesicles, which act as drug delivery vehicles and reduce the risk of exposure of drug to healthy cells(1). The sterility of such liposome solutions is typically ensured using 0.2μm rated sterilizing grade membranes, but due to the high viscosity and low surface tension of these formulations, they can cause pre-mature blocking and increased risk of bacterial penetration through a 0.2μm sterilizing grade membrane(2). The low surface tension of liposome solutions affects the contact angle with membrane and reduces bubble point leading to bacterial penetration through the membrane. This poses a great challenge to select an appropriate sterilizing grade membrane for a given process and for filter manufacturers to develop a sterilizing grade membrane that specifically addresses these needs. In this study, the influence of different variables that could affect the total throughput and bacterial retention performance of different membranes types on processing of liposome solutions have been evaluated. Based on the results, we conclude that the membrane properties e.g., surface porosity, surface tension, pore size, symmetry/asymmetry, hydrophilicity and liposome properties e.g., composition, lipid size and concentration affect bacterial retention and total throughput capacity. Process parameters such as temperature, pressure and flow should also be optimized to improve process efficiency. Copyright © 2017, Parenteral Drug Association.

  10. Target-specific binding of immunoliposomes in vivo

    International Nuclear Information System (INIS)

    Holmberg, E.; Maruyama, K.; Kennel, S.; Klibanov, A.; Torchilin, V.; Ryan, U.; Huang, L.; Oak Ridge National Lab., TN; Akademiya Meditsinskikh Nauk SSSR, Moscow; Miami Univ., FL; Tennessee Univ., Knoxville, TN

    1989-01-01

    Our group at the University of Tennessee has been concentrating on using monoclonal antibody for targeting of a liposomal drug carrier system. This paper discusses our initial effort to target these liposomes using an organ-specific monoclonal antibody. 9 refs., 9 figs

  11. Liposomal cancer therapy: exploiting tumor characteristics

    DEFF Research Database (Denmark)

    Kaasgaard, Thomas; Andresen, Thomas Lars

    2010-01-01

    an overview of current strategies for improving the different stages of liposomal cancer therapy, which involve transporting drug-loaded liposomes through the bloodstream, increasing tumor accumulation, and improving drug release and cancer cell uptake after accumulation at the tumor target site. What...... the reader will gain: The review focuses on strategies that exploit characteristic features of solid tumors, such as abnormal vasculature, overexpression of receptors and enzymes, as well as acidic and thiolytic characteristics of the tumor microenvironment. Take home message: It is concluded that the design...

  12. Mechanistic Studies on the Triggered Release of Liposomal Contents by Matrix Metalloproteinase-9

    Science.gov (United States)

    Elegbede, Adekunle I.; Banerjee, Jayati; Hanson, Andrea J.; Tobwala, Shakila; Ganguli, Bratati; Wang, Rongying; Lu, Xiaoning; Srivastava, D. K.; Mallik, Sanku

    2009-01-01

    Matrix metalloproteinases (MMPs) are a class of extracellular matrix degrading enzymes over-expressed in many cancers and contribute to the metastatic ability of the cancer cells. We have recently demonstrated that liposomal contents can be released when triggered by the enzyme MMP-9. Herein, we report our results on the mechanistic studies of the MMP-9 triggered release of the liposomal contents. We synthesized peptides containing the cleavage site for MMP-9 and conjugated them with fatty acids to prepare the corresponding lipopeptides. By employing Circular Dichroism spectroscopy, we demonstrate that the lipopeptides, when incorporated in liposomes, are de-mixed in the lipid bilayers and generate triple helical structures. MMP-9 cleaves the triple helical peptides, leading to the release of the liposomal contents. Other MMPs, which cannot hydrolyze triple helical peptides, failed to release the contents from the liposomes. We also observed that the rate and the extent of release of the liposomal contents depend on the mismatch between acyl chains of the synthesized lipopeptide and phospholipid components of the liposomes. Circular Dichroism spectroscopic studies imply that the observed differences in the release reflect the ability of the liposomal membrane to anneal the defects following the enzymatic cleavage of the liposome-incorporated lipopeptides. PMID:18642903

  13. Continuous-Flow Production of Injectable Liposomes via a Microfluidic Approach

    Science.gov (United States)

    Zizzari, Alessandra; Bianco, Monica; Perrone, Elisabetta; Amato, Francesco; Maruccio, Giuseppe; Rendina, Filippo; Arima, Valentina

    2017-01-01

    Injectable liposomes are characterized by a suitable size and unique lipid mixtures, which require time-consuming and nonstraightforward production processes. The complexity of the manufacturing methods may affect liposome solubility, the phase transition temperatures of the membranes, the average particle size, and the associated particle size distribution, with a possible impact on the drug encapsulation and release. By leveraging the precise steady-state control over the mixing of miscible liquids and a highly efficient heat transfer, microfluidic technology has proved to be an effective and direct methodology to produce liposomes. This approach results particularly efficient in reducing the number of the sizing steps, when compared to standard industrial methods. Here, Microfluidic Hydrodynamic Focusing chips were produced and used to form liposomes upon tuning experimental parameters such as lipids concentration and Flow-Rate-Ratios (FRRs). Although modelling evidenced the dependence of the laminar flow on the geometric constraints and the FRR conditions, for the specific formulation investigated in this study, the lipids concentration was identified as the primary factor influencing the size of the liposomes and their polydispersity index. This was attributed to a predominance of the bending elasticity modulus over the vesiculation index in the lipid mixture used. Eventually, liposomes of injectable size were produced using microfluidic one-pot synthesis in continuous flow. PMID:29232873

  14. Modification of wool surface by liposomes for dyeing with weld.

    Science.gov (United States)

    Montazer, Majid; Zolfaghari, Alireza; Toliat, Taibeh; Moghadam, Mohammad Bameni

    2009-01-01

    In this research work, wool surface has been modified by liposome to investigate its effects on dyeing with weld, a yellow natural dye. To do this, samples were first treated with aluminium sulphate and afterward with different concentrations of liposomes at various temperatures for 30 minutes and, finally, dyed with weld at 75, 85, and 95 degrees C for 30, 45, and 60 minutes. K/S values of fabric samples were calculated and washing, light and rub fastness properties of the samples were indicated. The results proposed that the sample treated with 1% liposomes and dyed at 75 degrees C for 60 min has the highest K/S value. The central composite design (CCD) used for the experimental plan with three variables on the results of color strength and statistical analysis confirms the optimum conditions obtained by the experimental results. It was also found that washing, light, wet, and dry rub fastness properties of samples dyed with weld, including liposomes, have not significantly changed. The results of water drop absorption indicated that the hydrophobicity is higher for the samples pretreated with liposomes. The SEM picture of wool sample treated with mordant and liposomes and finally dyed with weld shows a coated layer on the fiber surface.

  15. trimethylammoniumpropane-based Liposomes

    African Journals Online (AJOL)

    mechanisms to introduce therapeutic agents into the body. Currently, the ... Liposomes are biodegradable and non-toxic and can elicit both ... buffered saline by dissolving a vial in 40 ml phosphate ... vaccines were processed using copper grids to adsorb the .... time-dependent fluctuations in the intensity of scattered light ...

  16. Liposomes and lipid disks traverse the BBB and BBTB as intact forms as revealed by two-step Förster resonance energy transfer imaging

    Directory of Open Access Journals (Sweden)

    Tongcheng Dai

    2018-03-01

    Full Text Available The blood–brain barrier (BBB and the blood–brain tumor barrier (BBTB prevent drug and nano-drug delivery systems from entering the brain. However, ligand-mediated nano-drug delivery systems have significantly enhanced the therapeutic treatment of glioma. In this study we investigated the mechanism especially the integrity of liposomes and lipid disks while traversing the BBB and BBTB both in vitro and in vivo. Fluorophores (DiO, DiI and DiD were loaded into liposomes and lipid disks to form Förster resonance energy transfer (FRET nano-drug delivery systems. Using brain capillary endothelial cells as a BBB model, we show that liposomes and disks are present in the cytoplasm as their intact forms and traverse the BBB with a ratio of 0.68‰ and 1.67‰, respectively. Using human umbilical vein endothelial cells as BBTB model, liposomes and disks remained intact and traversed the BBTB with a ratio of 2.31‰ and 8.32‰ at 3 h. Ex vivo imaging and immunohistochemical results revealed that liposomes and disks could traverse the BBB and BBTB in vivo as intact forms. In conclusion, these observations explain in part the mechanism by which nano-drug delivery systems increase the therapeutic treatment of glioma. KEY WORDS: Liposomes, Disks, Intact form, BBB, BBTB, FRET

  17. Physical and Oxidative Stability of Uncoated and Chitosan-Coated Liposomes Containing Grape Seed Extract

    Directory of Open Access Journals (Sweden)

    Jochen Weiss

    2013-08-01

    Full Text Available Polyphenol-rich grape seed extract (0.1 w/w% was incorporated in liposomes (1 w/w% soy lecithin by high pressure homogenization (22,500 psi and coated with chitosan (0.1 w/w%. Primary liposomes and chitosan-coated secondary liposomes containing grape seed extract showed good physical stability during 98 days of storage. Most of the polyphenols were incorporated in the shell of the liposomes (85.4%, whereas only 7.6% of the polyphenols of grape seed extract were located in the interior of the liposomes. Coating with chitosan did not change the polyphenol content in the liposomes (86.6%. The uncoated liposomes without grape seed extract were highly prone to lipid oxidation. The cationic chitosan coating, however, improved the oxidative stability to some extent, due to its ability to repel pro-oxidant metals. Encapsulated grape seed extract showed high antioxidant activity in both primary and secondary liposomes, which may be attributed to its polyphenol content. In conclusion, the best chemical stability of liposomes can be achieved using a combination of grape seed extract and chitosan.

  18. Single-cell-based system to monitor carrier driven cellular auxin homeostasis

    Science.gov (United States)

    2013-01-01

    Background Abundance and distribution of the plant hormone auxin play important roles in plant development. Besides other metabolic processes, various auxin carriers control the cellular level of active auxin and, hence, are major regulators of cellular auxin homeostasis. Despite the developmental importance of auxin transporters, a simple medium-to-high throughput approach to assess carrier activities is still missing. Here we show that carrier driven depletion of cellular auxin correlates with reduced nuclear auxin signaling in tobacco Bright Yellow-2 (BY-2) cell cultures. Results We developed an easy to use transient single-cell-based system to detect carrier activity. We use the relative changes in signaling output of the auxin responsive promoter element DR5 to indirectly visualize auxin carrier activity. The feasibility of the transient approach was demonstrated by pharmacological and genetic interference with auxin signaling and transport. As a proof of concept, we provide visual evidence that the prominent auxin transport proteins PIN-FORMED (PIN)2 and PIN5 regulate cellular auxin homeostasis at the plasma membrane and endoplasmic reticulum (ER), respectively. Our data suggest that PIN2 and PIN5 have different sensitivities to the auxin transport inhibitor 1-naphthylphthalamic acid (NPA). Also the putative PIN-LIKES (PILS) auxin carrier activity at the ER is insensitive to NPA in our system, indicating that NPA blocks intercellular, but not intracellular auxin transport. Conclusions This single-cell-based system is a useful tool by which the activity of putative auxin carriers, such as PINs, PILS and WALLS ARE THIN1 (WAT1), can be indirectly visualized in a medium-to-high throughput manner. Moreover, our single cell system might be useful to investigate also other hormonal signaling pathways, such as cytokinin. PMID:23379388

  19. Polyelectrolyte stabilized multilayered liposomes for oral delivery of paclitaxel

    DEFF Research Database (Denmark)

    Jain, Sanyog; Kumar, Dinesh; Swarnakar, Nitin K

    2012-01-01

    Paclitaxel (PTX) loaded layersome formulations were prepared using layer-by-layer assembly of the polyelectrolytes over liposomes. Stearyl amine was utilized to provide positive charge to the liposomes, which were subsequently coated with anionic polymer polyacrylic acid (PAA) followed by coating...

  20. Noninvasive control of the transport function of fluorescent coloured liposomal nanoparticles

    Science.gov (United States)

    Stelmashchuk, O.; Zherebtsov, E.; Zherebtsova, A.; Kuznetsova, E.; Vinokurov, A.; Dunaev, A.; Mamoshin, A.; Snimshchikova, I.; Borsukov, A.; Bykov, A.; Meglinski, I.

    2017-06-01

    The use of liposomal nanoparticles with an incorporated active substance is an innovative and promising approach to diagnostics and therapy. The application of liposomal nanoparticle-based drugs allows for targeted localized delivery, overcomes the natural barriers within the body effectively, and minimizes possible side effects. Liposomes are able to contain a variety of ingredients with practically no limitations to their chemical composition, chemical properties, or size of constituent molecules. This study evaluated the ability to control the passage of fluorescent dye-filled liposomes through the intestinal mucosal barrier after oral administration. For this purpose, the increase in transcutaneous registered fluorescence from tetrabromofluorescein dye was recorded and analysed. Fluorescence intensity was measured at the proximal end of the tail of an animal model after oral administration of the liposomes. Measurements were taken at the excitation wavelengths of 365 and 450 nm. The fluorescence intensity in the group treated with the fluorescent contrast agent encapsulated in liposomal particles increased 140% of the initial level, but in the group treated with pure contrast agent, the increase in detected fluorescence intensity did not exceed 110%. Mice that received empty liposomes as well as the control group did not demonstrate statistically significant changes in fluorescence intensity. A potential application of our results is an express laser optical method of monitoring the transport of orally administered liposomal particles. The results can be used to help create new optical tools for use in the development of new drugs and in high-throughput screening used during their testing.

  1. Lipid nanoparticles as drug/gene delivery systems to the retina.

    Science.gov (United States)

    del Pozo-Rodríguez, Ana; Delgado, Diego; Gascón, Alicia R; Solinís, Maria Ángeles

    2013-03-01

    This review highlights the application of lipid nanoparticles (Solid Lipid Nanoparticles, Nanostructured Lipid Carriers, or Lipid Drug Conjugates) as effective drug/gene delivery systems for retinal diseases. Most drug products for ocular disease treatment are marketed as eye drop formulations but, due to ocular barriers, the drug concentration in the retina hardly ever turns out to be effective. Up to this date, several delivery systems have been designed to deliver drugs to the retina. Drug delivery strategies may be classified into 3 groups: noninvasive techniques, implants, and colloidal carriers. The best known systems for drug delivery to the posterior eye are intravitreal implants; in fact, some of them are being clinically used. However, their long-term accumulation might impact the patient's vision. On the contrary, colloidal drug delivery systems (microparticles, liposomes, or nanoparticles) can be easily administered in a liquid form. Nanoparticular systems diffuse rapidly and are better internalized in ocular tissues than microparticles. In comparison with liposomes, nanoparticles have a higher loading capacity and are more stable in biological fluids and during storage. In addition, their capacity to adhere to the ocular surface and interact with the endothelium makes these drug delivery systems interesting as new therapeutic tools in ophthalmology. Within the group of nanoparticles, those composed of lipids (Solid Lipid Nanoparticles, Nanostructred Lipid Carriers, and Lipid Drug Conjugates) are more biocompatible, easy to produce at large scale, and they may be autoclaved or sterilized. The present review summarizes scientific results that evidence the potential application of lipid nanoparticles as drug delivery systems for the retina and also as nonviral vectors in gene therapy of retina disorders, although much more effort is still needed before these lipidic systems could be available in the market.

  2. New approaches in the management of advanced breast cancer – role of combination treatment with liposomal doxorubicin

    Directory of Open Access Journals (Sweden)

    Iain RJ Macpherson

    2009-08-01

    Full Text Available Iain RJ Macpherson, TR Jeffry EvansBeatson West of Scotland Cancer Centre, Glasgow, United KingdomAbstract: Metastatic breast cancer (MBC remains a major cause of morbidity and mortality in women worldwide. For three decades doxorubicin, alone or in combination with other cytotoxic agents, has been a mainstay of systemic therapy for MBC. However, its use is limited by cumulative cardiotoxicity. More recently liposomal formulations of doxorubicin have been developed which exhibit equal efficacy but reduced cardiotoxicity in comparison to conventional doxorubicin. The novel toxicity profile of liposomal doxorubicins has prompted their evaluation with various cytotoxic agents in patients with MBC. In addition, their favorable cardiac safety profile has prompted re-evaluation of concomitant therapy with doxorubicin and trastuzumab, a regimen of proven efficacy in MBC but previously considered to be associated with significant cardiotoxicity. We review clinical trial data addressing combination therapy with both pegylated and non-pegylated liposomal doxorubicin in patients with MBC.Keywords: breast cancer, anthracycline, liposome-encapsulated doxorubicin, pegylated liposomal doxorubicin, cardiotoxicity

  3. Intracellular targeting of mercaptoundecahydrododecaborate (BSH) to malignant glioma by transferrin-PEG liposomes for boron neutron capture therapy (BNCT)

    International Nuclear Information System (INIS)

    Doi, Atsushi; Miyatake, Shin-ichi; Iida, Kyouko

    2006-01-01

    Malignant glioma is one of the most difficult tumor to control with usual therapies. In our institute, we select boron neutron capture therapy (BNCT) as an adjuvant radiation therapy after surgical resection. This therapy requires the selective delivery of high concentration of 10 B to malignant tumor tissue. In this study, we focused on a tumor-targeting 10 B delivery system (BDS) for BNCT that uses transferrin-conjugated polyethylene-glycol liposome encapsulating BSH (TF-PEG liposome-BSH) and compared 10 B uptake of the tumor among BSH, PEG liposome-BSH and TF-PEG liposome-BSH. In vitro, we analyzed 10 B concentration of the cultured human U87Δ glioma cells incubated in medium containing 20 μg 10 B/ml derived from each BDS by inductively coupled plasma atomic emission spectrometry (ICP-AES). In vivo, human U87Δ glioma-bearing nude mice were administered with each BDS (35mg 10 B/kg) intravenously. We analyzed 10 B concentration of tumor, normal brain and blood by ICP-AES. The TF-PEG liposome-BSH showed higher absolute concentration more than the other BDS. Moreover, TF-PEG liposome-BSH decreased 10 B concentration in blood and normal tissue while it maintained high 10 B concentration in tumor tissue for a couple of days. This showed the TF-PEG liposome-BSH caused the selective delivery of high concentration of 10 B to malignant tumor tissue. The TF-PEG liposome-BSH is more potent BDS for BNCT to obtain absolute high 10 B concentration and good contrast between tumor and normal tissue than BSH and PEG liposome-BSH. (author)

  4. Programmable fusion of liposomes mediated by lipidated PNA

    DEFF Research Database (Denmark)

    Rabe, A; Löffler, P M G; Ries, O

    2017-01-01

    We recently reported a DNA-programmed fusion cascade enabling the use of liposomes as nanoreactors for compartmentalized chemical reactions. This communication reports an alternative and robust strategy based on lipidated peptide nucleic acids (LiPs). LiPs enabled fusion of liposomes with remarka...... with remarkable 31% efficiency at 50 °C with low leakage (5%)....

  5. Liposomes for Use in Gene Delivery

    Directory of Open Access Journals (Sweden)

    Daniel A. Balazs

    2011-01-01

    Full Text Available Liposomes have a wide array of uses that have been continuously expanded and improved upon since first being observed to self-assemble into vesicular structures. These arrangements can be found in many shapes and sizes depending on lipid composition. Liposomes are often used to deliver a molecular cargo such as DNA for therapeutic benefit. The lipids used to form such lipoplexes can be cationic, anionic, neutral, or a mixture thereof. Herein physical packing parameters and specific lipids used for gene delivery will be discussed, with lipids classified according to overall charge.

  6. Preparation and quality evaluation of LHRHa-targeted Brucea javanica oil liposomes

    Directory of Open Access Journals (Sweden)

    Xiao-juan LIU

    2013-07-01

    Full Text Available Objective To prepare luteinizing hormone-releasing hormone a (LHRHa targeted Bruceajavanicaliposomes and evaluate its quality. Methods The LHRHa-targeted Bruceajavanicaliposome was prepared by thin layer dispersion together with biotin¬streptavidin bridge method. The optimum formation was selected by means of orthogonal design of experiment. The morphology of liposome was observed with transmission electron microscope. Zetasizer Nano ZS analyzer was used to measure the particle size and zeta potential. The entrapment efficiency was determined by ultra-violet spectroscopy and column chromatography. Centrifugal acceleration experiment and determination of leak rate were performed to prove the liposome stability. The targeting ability of liposome was appraised by cell experiment in vitro. Results The formed optimum formula was as follows: the ratio of lecithin to cholesterol was 4:1, Brucea javanicaoil:lipid was 3:10, DSPE-PEG (2000-Biotin:lecithin content was 3%, ultrasonic-homogenized for 8 minutes. Liposomes were round in shape, the average diameter and zeta potential of liposome were 155.1±14.5mm and –(24.1±0.54 mV, respectively. The average entrapment efficiency was 92.2%. Binding capacity with the A2780/DDP cell line in the LHRHa-targeted liposomes was 2.7 times higher than that in the non-targeting liposomes. Conclusion The technique of preparing LHRHa-targeted Bruceajavanicaliposome is suitable, and high in entrapment efficiency, with good stability and targeting ability.

  7. [Separate factors influencing the interaction of carbohydrate- containing liposomes with galactose-specific lectins].

    Science.gov (United States)

    Dvorkin, V M; Vidershaĭn, G Ia

    1984-11-01

    Some natural (Gal-Cer, Lac-Cer, desyalylated gangliosides) and synthetic (HMGal) glycolipids differing in the length of the bridge linking the terminal galactose with the hydrophobic moiety were incorporated into the liposome membranes. The precipitation of the thus obtained vesicles induced by galactose-specific lectin RCA was studied. It was shown that when the amount of the glycolipids used for the incorporation into the liposomes (1 mol. %) was the same, the vesicles with HMGal or Gal-Cer incorporated into them did not precipitate in the presence of lectin, whereas the liposomes with incorporated Lac-Cer or desyalylated gangliosides did precipitate. It was thus concluded that in order for galactose-containing liposomes precipitation by lectin RCA1 to be induced, galactose should be separated from the liposome membrane with a distance not less than 7 A. The nature of lectin-induced nonspecific precipitation of ganglioside-containing liposomes, ganglioside mycelles and cardiolipin-lecithine liposomes containing lactosylceramide was investigated. Some nonspecific ionic interactions of negatively charged liposomes and ganglioside mycelles with lectin were observed, which disappeared with a rise in the NaCl concentration up to 150-200 mM.

  8. Cyclodextrins in drug carrier systems.

    Science.gov (United States)

    Uekama, K; Otagiri, M

    1987-01-01

    One of the important characteristics of cyclodextrins is the formation of an inclusion complex with a variety of drug molecules in solution and in the solid state. As a consequence of intensive basic research, exhaustive toxic studies, and realization of industrial production during the past decade, there seem to be no more barriers for the practical application of natural cyclodextrins in the biomedical field. Recently, a number of cyclodextrin derivatives and cyclodextrin polymers have been prepared to obtain better inclusion abilities than parent cyclodextrins. The natural cyclodextrins and their synthetic derivatives have been successfully utilized to improve various drug properties, such as solubility, dissolution and release rates, stability, or bioavailability. In addition, the enhancement of drug activity, selective transfer, or the reduction of side effects has been achieved by means of inclusion complexation. The drug-cyclodextrin complex is generally formed outside of the body and, after administration, it dissociates, releasing the drug into the organism in a fast and nearly uniform manner. In the biomedical application of cyclodextrins, therefore, particular attention should be directed to the magnitude of the stability constant of the inclusion complex. In the case of parenteral application, a rather limited amount of work has been done because the cyclodextrins in the drug carrier systems have to be more effectively designed to compete with various biological components in the circulatory system. However, the works published thus far apparently indicate that the inclusion phenomena of cyclodextrin analogs may allow the rational design of drug formulation and that the combination of molecular encapsulation with other carrier systems will become a very effective and valuable method for the development of a new drug delivery system in the near future.

  9. Conventional and dense gas techniques for the production of liposomes: a review.

    Science.gov (United States)

    Meure, Louise A; Foster, Neil R; Dehghani, Fariba

    2008-01-01

    The aim of this review paper is to compare the potential of various techniques developed for production of homogenous, stable liposomes. Traditional techniques, such as Bangham, detergent depletion, ether/ethanol injection, reverse-phase evaporation and emulsion methods, were compared with the recent advanced techniques developed for liposome formation. The major hurdles for scaling up the traditional methods are the consumption of large quantities of volatile organic solvent, the stability and homogeneity of the liposomal product, as well as the lengthy multiple steps involved. The new methods have been designed to alleviate the current issues for liposome formulation. Dense gas liposome techniques are still in their infancy, however they have remarkable advantages in reducing the use of organic solvents, providing fast, single-stage production and producing stable, uniform liposomes. Techniques such as the membrane contactor and heating methods are also promising as they eliminate the use of organic solvent, however high temperature is still required for processing.

  10. Stimulus-responsive liposomes as smart nanoplatforms for drug delivery applications.

    Science.gov (United States)

    Zangabad, Parham Sahandi; Mirkiani, Soroush; Shahsavari, Shayan; Masoudi, Behrad; Masroor, Maryam; Hamed, Hamid; Jafari, Zahra; Taghipour, Yasamin Davatgaran; Hashemi, Hura; Karimi, Mahdi; Hamblin, Michael R

    2018-02-01

    Liposomes are known to be promising nanoparticles (NPs) for drug delivery applications. Among different types of self-assembled NPs, liposomes stand out for their non-toxic nature, and their possession of dual hydrophilic-hydrophobic domains. Advantages of liposomes include the ability to solubilize hydrophobic drugs, the ability to incorporate different hydrophilic and lipophilic drugs at the same time, lessening the exposure of host organs to potentially toxic drugs and allowing modification of the surface by a variety of different chemical groups. This modification of the surface, or of the individual constituents, may be used to achieve two important goals. Firstly, ligands for active targeting can be attached that are recognized by cognate receptors over-expressed on the target cells of tissues. Secondly, modification can be used to impart a stimulus-responsive or "smart" character to the liposomes, whereby the cargo is released on demand only when certain internal stimuli (pH, reducing agents, specific enzymes) or external stimuli (light, magnetic field or ultrasound) are present. Here, we review the field of smart liposomes for drug delivery applications.

  11. Studies on liposomes with Chlorophyll for monitoring the electromagnetic influence at molecular level

    International Nuclear Information System (INIS)

    Tugulea, Laura; Miclaus, Simona; Iacovache, Ioan

    2001-01-01

    The liposomes with Chlorophyll are excellent model membranes and could be successfully used to study the electromagnetic influence at molecular level. The strong visible absorption and fluorescence of Chlorophyll allow its use as sensor for the interactions at molecular level and as a fluorescence marker; it reflects certain aspects of the supramolecular structure of the lipid phase: fluidity, lipid and liposomes aggregation. The objective of our work was to evidence athermal effect of low level, pulsed microwave (MW) fields on liposomes and to evidence the possible mechanism of interaction at molecular level. Unilamellar liposomes were obtained from multilamellar vesicles by the hand-shaken method and sonication for 30 minutes. The multilamellar vesicles were prepared using Chla /lipid films with specific molar ratio (lipid/Chla 1/10 and 1/100) and different lipids (Dipalmitoyl phosphatidylcholine, Dimirystoyl Phosphatidylcholine and Dioleoyl Phosphatidylcholine-Sigma). The films were dispersed in buffer solutions of different pH (6.2 - 7.6). The Chlorophyll was freshly extracted from spinach leaves and separated by the chromatographic method. Portions of liposome suspension (0.6 ml) were inserted into Teflon cuvettes. The samples were irradiated in series, for periods of 5-30 minutes. The exposure system was: MW generator + adapted load (shortened rectangular waveguide) + Teflon cuvette filled with sample liquid. The effect of MW irradiation is not observable on multilamellar vesicles, but only on small unilamellar vesicles. The MW effect is athermal, verified by conventional heating in the same range of temperatures and results in enlarging the size of vesicles. The enlarging effect of MW is opposed to the effect of ultrasounds exposure. It is not clear if effects due to MW are proportional with exposure duration; it seems that this mostly depends on the type of lipid in vesicles. The UV and VIS spectra were recorded to observe the oxidation state of the

  12. Enhanced Ungual Permeation of Terbinafine HCl Delivered Through Liposome-Loaded Nail Lacquer Formulation Optimized by QbD Approach.

    Science.gov (United States)

    Shah, Viral H; Jobanputra, Amee

    2018-01-01

    The present investigation focused on developing, optimizing, and evaluating a novel liposome-loaded nail lacquer formulation for increasing the transungual permeation flux of terbinafine HCl for efficient treatment of onychomycosis. A three-factor, three-level, Box-Behnken design was employed for optimizing process and formulation parameters of liposomal formulation. Liposomes were formulated by thin film hydration technique followed by sonication. Drug to lipid ratio, sonication amplitude, and sonication time were screened as independent variables while particle size, PDI, entrapment efficiency, and zeta potential were selected as quality attributes for liposomal formulation. Multiple regression analysis was employed to construct a second-order quadratic polynomial equation and contour plots. Design space (overlay plot) was generated to optimize a liposomal system, with software-suggested levels of independent variables that could be transformed to desired responses. The optimized liposome formulation was characterized and dispersed in nail lacquer which was further evaluated for different parameters. Results depicted that the optimized terbinafine HCl-loaded liposome formulation exhibited particle size of 182 nm, PDI of 0.175, zeta potential of -26.8 mV, and entrapment efficiency of 80%. Transungual permeability flux of terbinafine HCl through liposome-dispersed nail lacquer formulation was observed to be significantly higher in comparison to nail lacquer with a permeation enhancer. The developed formulation was also observed to be as efficient as pure drug dispersion in its antifungal activity. Thus, it was concluded that the developed formulation can serve as an efficient tool for enhancing the permeability of terbinafine HCl across human nail plate thereby improving its therapeutic efficiency.

  13. Liposome Disruption Assay to Examine Lytic Properties of Biomolecules.

    Science.gov (United States)

    Jimah, John R; Schlesinger, Paul H; Tolia, Niraj H

    2017-08-05

    Proteins may have three dimensional structural or amino acid features that suggest a role in targeting and disrupting lipids within cell membranes. It is often necessary to experimentally investigate if these proteins and biomolecules are able to disrupt membranes in order to conclusively characterize the function of these biomolecules. Here, we describe an in vitro assay to evaluate the membrane lytic properties of proteins and biomolecules. Large unilamellar vesicles (liposomes) containing carboxyfluorescein at fluorescence-quenching concentrations are treated with the biomolecule of interest. A resulting increase in fluorescence due to leakage of the dye from liposomes and subsequent dilution in the buffer demonstrates that the biomolecule is sufficient for disrupting liposomes and membranes. Additionally, since liposome disruption may occur via pore-formation or via general solubilization of lipids similar to detergents, we provide a method to distinguish between these two mechanisms. Pore-formation can be identified and evaluated by examining the blockade of carboxyfluorescein release with dextran molecules that fit the pore. The methods described here were used to determine that the malaria vaccine candidate CelTOS and proapoptotic Bax disrupt liposomes by pore formation (Saito et al. , 2000; Jimah et al. , 2016). Since membrane lipid binding by a biomolecule precedes membrane disruption, we recommend the companion protocol: Jimah et al. , 2017.

  14. Continuous-Flow Production of Injectable Liposomes via a Microfluidic Approach

    Directory of Open Access Journals (Sweden)

    Alessandra Zizzari

    2017-12-01

    Full Text Available Injectable liposomes are characterized by a suitable size and unique lipid mixtures, which require time-consuming and nonstraightforward production processes. The complexity of the manufacturing methods may affect liposome solubility, the phase transition temperatures of the membranes, the average particle size, and the associated particle size distribution, with a possible impact on the drug encapsulation and release. By leveraging the precise steady-state control over the mixing of miscible liquids and a highly efficient heat transfer, microfluidic technology has proved to be an effective and direct methodology to produce liposomes. This approach results particularly efficient in reducing the number of the sizing steps, when compared to standard industrial methods. Here, Microfluidic Hydrodynamic Focusing chips were produced and used to form liposomes upon tuning experimental parameters such as lipids concentration and Flow-Rate-Ratios (FRRs. Although modelling evidenced the dependence of the laminar flow on the geometric constraints and the FRR conditions, for the specific formulation investigated in this study, the lipids concentration was identified as the primary factor influencing the size of the liposomes and their polydispersity index. This was attributed to a predominance of the bending elasticity modulus over the vesiculation index in the lipid mixture used. Eventually, liposomes of injectable size were produced using microfluidic one-pot synthesis in continuous flow.

  15. Intracellular ROS protection efficiency and free radical-scavenging activity of quercetin and quercetin-encapsulated liposomes.

    Science.gov (United States)

    Rezaei-Sadabady, Rogaie; Eidi, Akram; Zarghami, Nosratollah; Barzegar, Abolfazl

    2016-01-01

    Quercetin (3,5,7,3',4'-pentahydroxyflavone) is a natural bio-flavonoid originating from fruits, vegetables, seeds, berries, and tea. The antioxidant activity of quercetin and its protective effects against cardiovascular disorders, anti-cancer, anti-inflammatory, and anti-viral activities have been extensively documented; however, the clinical request of quercetin in cancer treatment is significantly limited due to its very poor delivery features. In order to increase the hydrophilicity and drug delivery capability, we encapsulated quercetin into liposomes. Our data indicated that liposomal quercetin can significantly improve the solubility and bioavailability of quercetin and can be used as an effective antioxidant for ROS protection within the polar cytoplasm, and the nano-sized quercetin encapsulated by liposomes enhanced the cellular uptake (cancer cell human MCF_7). Quercetin has many pharmaceutical applications, many of which arise from its potent antioxidant properties. The present research examined the antioxidant activities of quercetin in polar solvents by a comparative study using reduction of ferric iron in aqueous medium, intracellular ROS/toxicity assays, and reducing DPPH assays. Cell viability and ROS assays demonstrated that quercetin was able to penetrate into the polar medium inside the cells and to protect them against the highly toxic and deadly belongings of cumene hydroperoxide. The purpose of this study was to determine whether a liposomal formulation of quercetin can suggestively improve its solubility and bioavailability and can be a possible request in the treatment of tumor. The authors encapsulated quercetin in a liposomal delivery system. They studied the in vitro effects of this compound on proliferation using human MCF-7 carcinoma cells. The activity of liposomal quercetin was equal to or better than that of free quercetin at equimolar concentrations. Our data indicated that liposomal quercetin can significantly improve the

  16. Carrier system for a plant extract or bioactive compound from a plant

    DEFF Research Database (Denmark)

    2018-01-01

    This invention relates to a carrier system for use in producing a beverage with a metered amount of plant extract or bioactive compound.......This invention relates to a carrier system for use in producing a beverage with a metered amount of plant extract or bioactive compound....

  17. Inhibition of HIV Virus by Neutralizing Vhh Attached to Dual Functional Liposomes Encapsulating Dapivirine.

    Science.gov (United States)

    Wang, Scarlet Xiaoyan; Michiels, Johan; Ariën, Kevin K; New, Roger; Vanham, Guido; Roitt, Ivan

    2016-12-01

    Although highly active antiretroviral therapy (HAART) has greatly improved the life expectancy of HIV/AIDS patients, the treatment is not curative. It is a global challenge which fosters an urgent need to develop an effective drug or neutralizing antibody delivery approach for the prevention and treatment of this disease. Due to the low density of envelope spikes with restricted mobility present on the surface of HIV virus, which limit the antibody potency and allow virus mutation and escape from the immune system, it is important for a neutralizing antibody to form bivalent or multivalent bonds with the virus. Liposome constructs could fulfil this need due to the flexible mobility of the membrane with its attached antibodies and the capacity for drug encapsulation. In this study, we evaluated the neutralization activity of a range of liposome formulations in different sizes coated with anti-gp120 llama antibody fragments (Vhhs) conjugated via either non-covalent metal chelation or a covalent linkage. The non-covalent construct demonstrated identical binding affinity to HIV-1 envelope glycoprotein gp120 and neutralizing ability for HIV virus as free Vhh. Although covalently linked Vhh showed significant binding affinity to gp120, it unexpectedly had a lower neutralization potency. This may be due to the comparability in size of the viral and liposome particles restricting the number which can be bound to the liposome surface so involving only a fraction of the antibodies, whereas non-covalently attached antibodies dissociate from the surface after acting with gp120 and free the remainder to bind further viruses. Covalently conjugated Vhh might also trigger the cellular uptake of a liposome-virion complex. To explore the possible ability of the antibody-coated liposomes to have a further function, we encapsulated the hydrophobic antiviral drug dapivirine into both of the non-covalently and covalently conjugated liposome formulations, both of which revealed high

  18. Inhibition of HIV Virus by Neutralizing Vhh Attached to Dual Functional Liposomes Encapsulating Dapivirine

    Science.gov (United States)

    Wang, Scarlet Xiaoyan; Michiels, Johan; Ariën, Kevin K.; New, Roger; Vanham, Guido; Roitt, Ivan

    2016-07-01

    Although highly active antiretroviral therapy (HAART) has greatly improved the life expectancy of HIV/AIDS patients, the treatment is not curative. It is a global challenge which fosters an urgent need to develop an effective drug or neutralizing antibody delivery approach for the prevention and treatment of this disease. Due to the low density of envelope spikes with restricted mobility present on the surface of HIV virus, which limit the antibody potency and allow virus mutation and escape from the immune system, it is important for a neutralizing antibody to form bivalent or multivalent bonds with the virus. Liposome constructs could fulfil this need due to the flexible mobility of the membrane with its attached antibodies and the capacity for drug encapsulation. In this study, we evaluated the neutralization activity of a range of liposome formulations in different sizes coated with anti-gp120 llama antibody fragments (Vhhs) conjugated via either non-covalent metal chelation or a covalent linkage. The non-covalent construct demonstrated identical binding affinity to HIV-1 envelope glycoprotein gp120 and neutralizing ability for HIV virus as free Vhh. Although covalently linked Vhh showed significant binding affinity to gp120, it unexpectedly had a lower neutralization potency. This may be due to the comparability in size of the viral and liposome particles restricting the number which can be bound to the liposome surface so involving only a fraction of the antibodies, whereas non-covalently attached antibodies dissociate from the surface after acting with gp120 and free the remainder to bind further viruses. Covalently conjugated Vhh might also trigger the cellular uptake of a liposome-virion complex. To explore the possible ability of the antibody-coated liposomes to have a further function, we encapsulated the hydrophobic antiviral drug dapivirine into both of the non-covalently and covalently conjugated liposome formulations, both of which revealed high

  19. Modeling cell membrane transport: interaction of guanidinylated poly(propylene imine) dendrimers with a liposomal membrane consisting of phosphate-based lipids.

    Science.gov (United States)

    Tsogas, Ioannis; Tsiourvas, Dimitris; Nounesis, George; Paleos, Constantinos M

    2006-12-19

    Mixed anionic liposomes consisting of dihexadecyl phosphate, phosphatidylcholine, and cholesterol were employed as model systems for assessing the ability of a series of functionalized dendrimers, bearing a varying number of guanidinium groups at their surface, to translocate across the liposomal bilayers. At low guanidinium/phosphate molar ratios or when weakly guanidinylated dendrimeric derivatives were employed, the dendrimeric derivative acted as a kind of "molecular glue" leading to a simple adhesion of the liposomes. Liposomal fusion occurred to a certain extent at high guanidinium/phosphate molar ratios or when highly guanidinylated dendrimeric derivatives were employed. Furthermore, translocation of these dendrimeric derivatives to the liposomal core was observed for low to medium guanidinylation and at low guanidinium/phosphate molar ratios which was, however, enhanced when the lipid bilayer was in its fluid liquid-crystalline phase. Thus, an optimum balance is required between the binding strength of guanidinium with the phosphate groups and the degree of hydrophilicity of the guanidinylated dendrimers for the transport of the latter to the liposomal core to occur.

  20. Enhanced bactericidal potency of nanoliposomes by modification of the fusion activity between liposomes and bacterium

    Directory of Open Access Journals (Sweden)

    Ma YF

    2013-06-01

    Full Text Available Yufan Ma,1 Zhao Wang,1,2 Wen Zhao,1 Tingli Lu,1 Rutao Wang,1,2 Qibing Mei,1 Tao Chen1–3 1Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, People's Republic of China; 2Shaanxi Liposome Research Center, Xi'an, Shaanxi, People's Republic of China; 3Xi'an Libang Pharmaceuticals Co, Ltd, Xi'an, People's Republic of China Background: Pseudomonas aeruginosa represents a good model of antibiotic resistance. These organisms have an outer membrane with a low level of permeability to drugs that is often combined with multidrug efflux pumps, enzymatic inactivation of the drug, or alteration of its molecular target. The acute and growing problem of antibiotic resistance of Pseudomonas to conventional antibiotics made it imperative to develop new liposome formulations to overcome these mechanisms, and investigate the fusion between liposome and bacterium. Methods: The rigidity, stability and charge properties of phospholipid vesicles were modified by varying the cholesterol, 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE, and negatively charged lipids 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol sodium salt (DMPG, 1,2-dimyristoyl-sn-glycero-3-phopho-L-serine sodium salt (DMPS, 1,2-dimyristoyl-sn-glycero-3-phosphate monosodium salt (DMPA, nature phosphatidylserine sodium salt from brain and nature phosphatidylinositol sodium salt from soybean concentrations in liposomes. Liposomal fusion with intact bacteria was monitored using a lipid-mixing assay. Results: It was discovered that the fluid liposomes-bacterium fusion is not dependent on liposomal size and lamellarity. A similar degree of fusion was observed for liposomes with a particle size from 100 to 800 nm. The fluidity of liposomes is an essential pre-request for liposomes fusion with bacteria. Fusion was almost completely inhibited by incorporation of cholesterol into fluid liposomes. The increase in the

  1. Liposomal delivery of radionuclides for cancer diagnostics and radiotherapy

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa

    , an in vivo study is presented, where passive tumor accumulation of 64Cu loaded liposomes (64Cu-liposomes) in tumor-bearing mice was quantified directly by PET and computed tomography (CT) imaging. Furthermore, Article I present an evaluation and quantitative measurement of the biodistribution of 64Cu...

  2. Improved permeability of acyclovir: optimization of mucoadhesive liposomes using the phospholipid vesicle-based permeation assay.

    Science.gov (United States)

    Naderkhani, Elenaz; Erber, Astrid; Škalko-Basnet, Nataša; Flaten, Gøril Eide

    2014-02-01

    The antiviral drug acyclovir (ACV) suffers from poor solubility both in lipophilic and hydrophilic environment, leading to low and highly variable bioavailability. To overcome these limitations, this study aimed at designing mucoadhesive ACV-containing liposomes to improve its permeability. Liposomes were prepared from egg phosphatidylcholine (E-PC) and E-PC/egg phosphatidylglycerol (E-PC/E-PG) and their surfaces coated with Carbopol. All liposomal formulations were fully characterized and for the first time the phospholipid vesicle-based permeation assay (PVPA) was used for testing in vitro permeability of drug from mucoadhesive liposome formulations. The negatively charged E-PC/E-PG liposomes could encapsulate more ACV than neutral E-PC liposomes. Coating with Carbopol increased the entrapment in the neutral E-PC liposomes. The incorporation of ACV into liposomes exhibited significant increase in its in vitro permeability, compared with its aqueous solution. The neutral E-PC liposomal formulations exhibited higher ACV permeability values compared with charged E-PC/E-PG formulations. Coating with Carbopol significantly enhanced the permeability from the E-PC/E-PG liposomes, as well as sonicated E-PC liposomes, which showed the highest permeability of all tested formulations. The increased permeability was according to the formulations' mucoadhesive properties. This indicates that the PVPA is suitable to distinguish between permeability of ACV from different mucoadhesive liposome formulations developed for various routes of administration. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  3. A polymeric fastener can easily functionalize liposome surfaces with gadolinium for enhanced magnetic resonance imaging.

    Science.gov (United States)

    Smith, Cartney E; Shkumatov, Artem; Withers, Sarah G; Yang, Binxia; Glockner, James F; Misra, Sanjay; Roy, Edward J; Wong, Chun-Ho; Zimmerman, Steven C; Kong, Hyunjoon

    2013-11-26

    Common methods of loading magnetic resonance imaging (MRI) contrast agents into nanoparticles often suffer from challenges related to particle formation, complex chemical modification/purification steps, and reduced contrast efficiency. This study presents a simple, yet advanced process to address these issues by loading gadolinium, an MRI contrast agent, exclusively on a liposome surface using a polymeric fastener. The fastener, so named for its ability to physically link the two functional components together, consisted of chitosan substituted with diethylenetriaminepentaacetic acid (DTPA) to chelate gadolinium, as well as octadecyl chains to stabilize the modified chitosan on the liposome surface. The assembly strategy, mimicking the mechanisms by which viruses and proteins naturally anchor to a cell, provided greater T1 relaxivity than liposomes loaded with gadolinium in both the interior and outer leaflet. Gadolinium-coated liposomes were ultimately evaluated in vivo using murine ischemia models to highlight the diagnostic capability of the system. Taken together, this process decouples particle assembly and functionalization and, therefore, has considerable potential to enhance imaging quality while alleviating many of the difficulties associated with multifunctional particle fabrication.

  4. Oxidative stability of Liposomes composed of docosahexaenoic acid-containing phospholipids

    DEFF Research Database (Denmark)

    Vikbjerg, Anders Falk; Andresen, Thomas Lars; Jørgensen, Kent

    2007-01-01

    Oxidative stability of liposomes made of (Docosahexaenoic acid) DHA-containing phosphatidylcholine (PC) was examined during preparation and storage. After preparation of the liposomes, the concentration of primary (conjugated dienes) and secondary oxidation products (Thiobarbituric acid...

  5. System and carrier for optical images and holographic information recording

    International Nuclear Information System (INIS)

    Andries, A.; Bivol, V.; Iovu, M

    2002-01-01

    The invention relates to the semiconducting silverless photography, in particular to the technique for optical information recording and may be used in microphotography for manifacture of microfiches, microfilms, storage disks, i the multiplication and copying technique, in holography, in micro- and optoelectronics, cinematography etc. The system for optical images and holographic information recording includes an optical exposure system, an information carrier , containing a dielectric substrate with the first electrode, a photosensitive element and the second electrode, arranged in consecutive order, a constant and impulse voltage source, a means for climbing and movement of the information carrier, a control unit for connection of the voltage source to the electroconducting strate, a personal computer, connected to the control unit of the recording modes ,to the exposure system and the information carrier, an electrooptical transparency, connected to the computer by means of the matching unit. The carrier for optical images and holographic information recording contains a dielectric substrate, a photosensitive element formed of a layer of the vitreous chalcogenic semiconductor and a layer of the crystalline or amorphous semiconductor, forming a heterojunction, the photosensitive element is arranged between two electrodes , one of which is made transparent , in such case rge layer of the vitreous chalcogenic semiconductor comes into contact with the superior transparent electrode, subjected to exposure

  6. Highly penetrative liposome nanomedicine generated by a biomimetic strategy for enhanced cancer chemotherapy.

    Science.gov (United States)

    Jia, Yali; Sheng, Zonghai; Hu, Dehong; Yan, Fei; Zhu, Mingting; Gao, Guanhui; Wang, Pan; Liu, Xin; Wang, Xiaobing; Zheng, Hairong

    2018-04-25

    Liposome nanomedicine has been successfully applied for cancer chemotherapy in patients. However, in general, the therapeutic efficacy is confined by its limited accumulation and penetration in solid tumors. Here, we established a biomimetic strategy for the preparation of highly penetrative liposome nanomedicine for enhanced chemotherapeutic efficacy. By applying this unique type of nanomedicine, membrane proteins on the cancer cells are used as highly penetrative targeting ligands. Biomimetic liposomes are highly stable, exhibiting a superior in vitro homologous targeting ability, and a 2.25-fold deeper penetration in 3D tumor spheroids when compared to conventional liposome nanomedicine. The fluorescence/photoacoustic dual-modal imaging approach demonstrated enhanced tumor accumulation and improved tumor penetration of the biomimetic liposome in C6 glioma tumor-bearing nude mice. Following the intravenous administration of biomimetic liposome nanomedicine, the tumor inhibition rate reached up to 93.3%, which was significantly higher when compared to that of conventional liposome nanomedicine (69.3%). Moreover, histopathological analyses demonstrated that biomimetic liposome nanomedicine has limited side effects. Therefore, these results suggested that a cancer cell membrane-based biomimetic strategy may provide a breakthrough approach for enhancing drug penetration and improving treatment efficacy, holding a great promise for further clinical studies.

  7. Targeting to cells of fluorescent liposomes covalently coupled with monoclonal antibody or protein A

    Science.gov (United States)

    Leserman, Lee D.; Barbet, Jacques; Kourilsky, François; Weinstein, John N.

    1980-12-01

    Many applications envisioned for liposomes in cell biology and chemotherapy require their direction to specific cellular targets1-3. The ability to use antibody as a means of conferring specificity to liposomes would markedly increase their usefulness. We report here a method for covalently coupling soluble proteins, including monoclonal antibody and Staphylococcus aureus protein A (ref. 4), to small sonicated liposomes, by using the heterobifunctional cross-linking reagent N-hydroxysuccinimidyl 3-(2-pyridyldithio)propionate (SPDP, Pharmacia). Liposomes bearing covalently coupled mouse monoclonal antibody against human β2-microglobulin [antibody B1.1G6 (IgG2a, κ) (B. Malissen et al., in preparation)] bound specifically to human, but not to mouse cells. Liposomes bearing protein A became bound to human cells previously incubated with the B1.1G6 antibody, but not to cells incubated without antibody. The coupling method results in efficient binding of protein to the liposomes without aggregation and without denaturation of the coupled ligand; at least 60% of liposomes bound functional protein. Further, liposomes did not leak encapsulated carboxyfluorescein (CF) as a consequence of the reaction.

  8. Preparation of 99mTc-HYNIC-PEG-liposomes for imaging of the focal sites infection

    International Nuclear Information System (INIS)

    Hong, Jun Pyo; Awh, Ok Doo; Kim, Hyun Suk; Lee, Eun Sook; Lee, Tae Sup; Choi, Tae Hyun; Choi, Chang Woon; Lim, Sang Moo

    2002-01-01

    A new linker, hydrazino nicotinamide (HYNIC), was recently introduced for labelling of liposome with 99m Tc. In this study we synthesized HYNIC derivatized PEG (polyethylene glycol)-liposomes radiolabeled with 99m Tc. In order to synthesize HYNIC-DSPE (distearoyl phosphatidyl ethanolamine) which is a crucial component for 99m Tc chelation, first of all succinimidyl 6-BOC-hydrazinopyridine-3-carboxylic acid was synthesized from 6-chloronicotinic acid by three sequential reactions. A DSPE derivative of succinimidyl 6-BOC-hydrazinopyridine-3-carboxylic acid was transformed into HYNIC-DSPE by HCI/dioxane. HYNIC-PEG-liposomes were prepared by hydration of the dried lipid mixture of EPC (egg phosphatidyl choline): PEG-DSPE : HYNIC-DSPE: cholesterol (1.85:0.15:0.07:1, molar ratio). The HYNIC-PEG-liposomes were labeled with 99m Tc in the presence of SnCl 2 ·2H 2 O (a reducing agent) and tricine (a colignad). To investigate the level of in vivo transchelation of 99m Tc in the liposomes, the 99m Tc-HYNIC-PEG-liposomes were incubated with a molar excess of DTPA, cysteine or glutathione solutions at 37 .deg. C for 24 hours. 6-BOC-hydrazinopyridine-3-carboxylic acid was synthesized with 77.3% overall yield. The HYNIC concentration in the PEG-coated liposome dispersion was 1.08 mM. In condition of considering the measured liposome size of 106 nm, the phospholipid concentration of 77.5 μmol/ ml and the liposomal particle number of 5.2x10 14 liposomes/ml, it is corresponded to approximate 1,250 nicotinyl hydrazine group per liposome in HYNIC-PEG-liposome. The removal of free 99m Tc was not necessary because the labeling efficiency were above 99%. The radiolabeled liposomes maintained 98%, 96% and 99%, respectively, of radioactivity after incubation with transchelators. The radiolabeled liposomes possessed above 90% of the radioactivity in serum. These results suggest that the HYNIC can be synthesized easily and applied in labelling of PEG-liposomes with 99m Tc

  9. Gd(III)-DOTA-modified sonosensitive liposomes for ultrasound-triggered release and MR imaging

    Science.gov (United States)

    Jung, Suk Hyun; Na, Kyunga; Lee, Seul A.; Cho, Sun Hang; Seong, Hasoo; Shin, Byung Cheol

    2012-08-01

    Ultrasound-sensitive (sonosensitive) liposomes for tumor targeting have been studied in order to increase the antitumor efficacy of drugs and decrease the associated severe side effects. Liposomal contrast agents having Gd(III) are known as a nano-contrast agent system for the efficient and selective delivery of contrast agents into pathological sites. The objective of this study was to prepare Gd(III)-DOTA-modified sonosensitive liposomes (GdSL), which could deliver a model drug, doxorubicin (DOX), to a specific site and, at the same time, be capable of magnetic resonance (MR) imaging. The GdSL was prepared using synthesized Gd(III)-DOTA-1,2-distearoyl- sn-glycero-3-phosphoethanolamine lipid. Sonosensitivity of GdSL to 20-kHz ultrasound induced 33% to 40% of DOX release. The relaxivities ( r 1) of GdSL were 6.6 to 7.8 mM-1 s-1, which were higher than that of MR-bester®. Intracellular uptake properties of GdSL were evaluated according to the intensity of ultrasound. Intracellular uptake of DOX for ultrasound-triggered GdSL was higher than that for non-ultrasound-triggered GdSL. The results of our study suggest that the paramagnetic and sonosensitive liposomes, GdSL, may provide a versatile platform for molecular imaging and targeted drug delivery.

  10. Potentiating Effects of MPL on DSPC Bearing Cationic Liposomes Promote Recombinant GP63 Vaccine Efficacy: High Immunogenicity and Protection

    Science.gov (United States)

    Mazumder, Saumyabrata; Maji, Mithun; Ali, Nahid

    2011-01-01

    Background Vaccines that activate strong specific Th1-predominant immune responses are critically needed for many intracellular pathogens, including Leishmania. The requirement for sustained and efficient vaccination against leishmaniasis is to formulate the best combination of immunopotentiating adjuvant with the stable antigen (Ag) delivery system. The aim of the present study is to evaluate the effectiveness of an immunomodulator on liposomal Ag through subcutaneous (s.c.) route of immunization, and its usefulness during prime/boost against visceral leishmaniasis (VL) in BALB/c mice. Methodology/Principal Findings Towards this goal, we formulated recombinant GP63 (rGP63)-based vaccines either with monophosphoryl lipid A-trehalose dicorynomycolate (MPL-TDM) or entrapped within cationic liposomes or both. Combinatorial administration of liposomes with MPL-TDM during prime confers activation of dendritic cells, and induces an early robust T cell response. To investigate whether the combined formulation is required for optimum immune response during boost as well, we chose to evaluate the vaccine efficacy in mice primed with combined adjuvant system followed by boosting with either rGP63 alone, in association with MPL-TDM, liposomes or both. We provide evidences that the presence of either liposomal rGP63 or combined formulations during boost is necessary for effective Th1 immune responses (IFN-γ, IL-12, NO) before challenge infection. However, boosting with MPL-TDM in conjugation with liposomal rGP63 resulted in a greater number of IFN-γ producing effector T cells, significantly higher levels of splenocyte proliferation, and Th1 responses compared to mice boosted with liposomal rGP63, after virulent Leishmania donovani (L. donovani) challenge. Moreover, combined formulations offered superior protection against intracellular amastigote replication in macrophages in vitro, and hepatic and splenic parasite load in vivo. Conclusion Our results define the

  11. Oleanolic acid liposomes with polyethylene glycol modification: promising antitumor drug delivery

    Directory of Open Access Journals (Sweden)

    Gao D

    2012-07-01

    Full Text Available Dawei Gao, Shengnan Tang, Qi TongApplied Chemical Key Laboratory of Hebei Province, College of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao, ChinaBackground: Oleanolic acid is a pentacyclic triterpene present in many fruits and vegetables, and has received much attention on account of its biological properties. However, its poor solubility and low bioavailability limit its use. The objective of this study was to encapsulate oleanolic acid into nanoliposomes using the modified ethanol injection method.Methods: The liposomes contain a hydrophobic oleanolic acid core, an amphiphilic soybean lecithin monolayer, and a protective hydrophilic polyethylene glycol (PEG coating. During the preparation process, the formulations described were investigated by designing 34 orthogonal experiments as well as considering the effects of different physical characteristics. The four factors were the ratios of drug to soybean phosphatidylcholine (w/w, cholesterol (w/w, PEG-2000 (w/w, and temperature of phosphate-buffered saline at three different levels. We identified the optimized formulation which showed the most satisfactory lipid stability and particle formation. The morphology of the liposomes obtained was determined by transmission electron microscopy and atomic force microscopy. The existence of PEG in the liposome component was validated by Fourier transform infrared spectrum analysis.Results: The PEGylated liposomes dispersed individually and had diameters of around 110–200 nm. Encapsulation efficiency was more than 85%, as calculated by high-performance liquid chromatography and Sephadex® gel filtration. Furthermore, when compared with native oleanolic acid, the liposomal formulations showed better stability in vitro. Finally, the cytotoxicity of the oleanolic acid liposomes was evaluated using a microtiter tetrazolium assay.Conclusion: These results suggest that PEGylated liposomes would serve as a potent delivery vehicle

  12. Radioprotective activity of curcumin-encapsulated liposomes against genotoxicity caused by Gamma Cobalt-60 irradiation in human blood cells.

    Science.gov (United States)

    Nguyen, Minh-Hiep; Pham, Ngoc-Duy; Dong, Bingxue; Nguyen, Thi-Huynh-Nga; Bui, Chi-Bao; Hadinoto, Kunn

    2017-11-01

    While the radioprotective activity of curcumin against genotoxicity has been well established, its poor oral bioavailability has limited its successful clinical applications. Nanoscale formulations, including liposomes, have been demonstrated to improve curcumin bioavailability. The objective of the present work was (1) to prepare and characterize curcumin-encapsulated liposomes (i.e. size, colloidal stability, encapsulation efficiency, and payload), and (2) subsequently to evaluate their radioprotective activity against genotoxicity in human blood cells caused by Gamma Cobalt-60 irradiation. The curcumin-encapsulated liposomes were prepared by lipid-film hydration method using commercial phosphatidylcholine (i.e. Phospholipon ® 90G). The blood cells were obtained from healthy male donors (n = 3) under an approved ethics protocol. The cell uptake and the radioprotective activity of the curcumin-encapsulated liposomes were characterized by fluorescence microscopy and micronucleus assay, respectively. Nanoscale curcumin-encapsulated liposomes exhibiting good physical characteristics and successful uptake by the human blood cells were successfully prepared. The radioprotective activity of the curcumin-encapsulated liposomes was found to be dependent on the curcumin concentration, where an optimal concentration existed (i.e. 30 μg/mL) independent of the irradiation dose, above which the radioprotective activity had become stagnant (i.e. no more reduction in the micronuclei frequency). The present results established for the first time the radioprotective activity of curcumin-encapsulated liposomes in human blood cells, which coupled by its well-established bioavailability, boded well for its potential application as a nanoscale delivery system of other radioprotective phytochemicals.

  13. Affinity Induced Surface Functionalization of Liposomes Using Cu-Free Click Chemistry

    DEFF Research Database (Denmark)

    Bak, Martin; Jølck, Rasmus Irming; Eliasen, Rasmus

    2016-01-01

    Functionalization of nanoparticles is a key element for improving specificity of drug delivery systems toward diseased tissue or cells. In the current study we report a highly efficient and chemoselective method for post-functionalization of liposomes with biomacromolecules, which equally well ca...

  14. A targeting drug-delivery model via interactions among cells and liposomes under ultrasonic excitation

    International Nuclear Information System (INIS)

    Xi Xiaoyu; Zhang Dong; Yang Fang; Gu Ning; Chen Di; Wu Junru; Luo Yi

    2008-01-01

    In our previous work, it was found that acoustic cavitation might play a role in improving the cell permeability to microparticles when liposomes were used in an in vitro experiment. The purpose of this project is to expand our study and to learn other possible mechanisms by which cells may interact with liposomes under ultrasound (US) excitation and become transiently permeable to microparticles. It is further hypothesized that two possible scenarios may be involved in in vitro experiments: (1) drug-carrying liposomes transiently overcome the cell membrane barrier and enter into a cell while the cell is still viable; (2) the liposomes incorporate with a cell at its membrane through a fusing process. To prove this hypothesis, liposomes of two different structures were synthesized: one has fluorescent molecules encapsulated into liposomes and the other has fluorescent markers incorporated into the shells of liposomes. Liposomes of each kind were mixed with human breast cancer cells (MCF7-cell line) in a suspension at 5 (liposomes) : 1 (cell) ratio and were then exposed to a focused 1 MHz ultrasound beam at its focal region for 40 s. The US signal contained 20 cycles per tone-burst at a pulse-repetition-frequency of 10 kHz; the spatial peak acoustic pressure amplitude was 0.25 MPa. It was found that the possible mechanisms might include the acoustic cavitation, the endocytosis and cell-fusion. Acoustic radiation force might make liposomes collide with cells effectively and facilitate the delivery process

  15. Liposomalization of oxaliplatin induces skin accumulation of it, but negligible skin toxicity.

    Science.gov (United States)

    Nishida, Kentaro; Kashiwagi, Misaki; Shiba, Shunsuke; Muroki, Kiwamu; Ohishi, Akihiro; Doi, Yusuke; Ando, Hidenori; Ishida, Tatsuhiro; Nagasawa, Kazuki

    2017-12-15

    Liposomalization causes alteration of the pharmacokinetics of encapsulated drugs, and allows delivery to tumor tissues through passive targeting via an enhanced permeation and retention (EPR) effect. PEGylated liposomal doxorubicin (Doxil ® , Lipo-DXR), a representative liposomal drug, is well-known to reduce cardiotoxicity and increase the anti-tumor activity of DXR, but to induce the hand-foot syndrome (HFS) as a result of skin DXR accumulation, which is one of its severe adverse effects. We have developed a new liposomal preparation of oxaliplatin (l-OHP), an important anti-tumor drug for treatment of colorectal cancer, using PEGylated liposomes (Lipo-l-OHP), and showed that Lipo-l-OHP exhibits increased anti-tumor activity in tumor-bearing mice compared to the original preparation of l-OHP. However, whether Lipo-l-OHP causes HFS-like skin toxicity similar to Lipo-DXR remains to be determined. Administration of Lipo-l-OHP promoted accumulation of platinum in rat hind paws, however, it caused negligible morphological and histological alterations on the plantar surface of the paws. Administration of DiI-labeled empty PEGylated liposomes gave almost the same distribution profile of dyes into the dermis of hind paws with DXR as in the case of Lipo-DXR. Treatment with Lipo-l-OHP, Lipo-DXR, DiI-labeled empty PEGylated liposomes or empty PEGylated liposomes caused migration of CD68 + macrophages into the dermis of hind paws. These findings suggest that the skin toxicity on administration of liposomalized drugs is reflected in the proinflammatory characteristics of encapsulated drugs, and indicate that Lipo-l-OHP with a higher anti-cancer effect and no HFS may be an outstanding l-OHP preparation leading to an improved quality of life of cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Recurrent Candida albicans Ventriculitis Treated with Intraventricular Liposomal Amphotericin B

    Directory of Open Access Journals (Sweden)

    Demet Toprak

    2015-01-01

    Full Text Available Central nervous system (CNS infection with Candida is rare but significant because of its high morbidity and mortality. When present, it is commonly seen among immunocompromised and hospitalized patients. Herein, we describe a case of a four-year-old boy with acute lymphoblastic leukemia (ALL who experienced recurrent Candida albicans meningitis. The patient was treated successfully with intravenous liposomal amphotericin B at first attack, but 25 days after discharge he was readmitted to hospital with symptoms of meningitis. Candida albicans was grown in CFS culture again and cranial magnetic resonance imaging (MRI showed ventriculitis. We administered liposomal amphotericin B both intravenously and intraventricularly and favorable result was achieved without any adverse effects. Intraventricular amphotericin B may be considered for the treatment of recurrent CNS Candida infections in addition to intravenous administration.

  17. Neurologic complications of intrathecal liposomal cytarabine administered prophylactically to patients with non-Hodgkin lymphoma.

    Science.gov (United States)

    Gállego Pérez-Larraya, Jaime; Palma, José Alberto; Carmona-Iragui, María; Fernández-Torrón, Roberto; Irimia, Pablo; Rodríguez-Otero, Paula; Panizo, Carlos; Martínez-Vila, Eduardo

    2011-07-01

    Central nervous system (CNS) prophylaxis is required during initial treatment of non-Hodgkin lymphoma (NHL) subtypes that carry a high risk of CNS involvement. Intrathecal (IT) liposomal cytarabine, a formulation with prolonged half-life, has been shown to be safe and effective in the treatment of meningeal disease in patients with high-grade lymphoma. We retrospectively reviewed all adult patients with high-grade NHL that received prophylactic therapy with IT liposomal cytarabine and developed neurologic complications in our institution between April 2007 and May 2009. We recorded information on hospital admission, chemotherapy regimens, clinical features, neuroimaging, cerebrospinal fluid, neurophysiology data, and outcome. Neurotoxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC). Four of fourteen patients (28%) developed moderate or severe neurotoxicity (grades 2 and 3 of the NCI-CTC), manifested as conus medullaris/cauda equine syndrome or pseudotumour cerebri-like syndrome, after a median of 3.5 IT courses of liposomal cytarabine. All patients had received corticosteroids to prevent arachnoiditis. Liposomal cytarabine given via the IT route, even with concomitant corticosteroid administration, can result in significant neurotoxicity in some patients. We discuss the potential pathogenesis of these effects and suggest hypothetical therapeutic measures to prevent these complications. Specialists should be aware of these possible complications when administering prophylactic IT liposomal cytarabine in high-grade NHL patients, and additional prospective studies should be conducted to more clearly delineate the frequency and characteristics of these complications.

  18. Highly-efficient liposome-mediated transformation system for the basidiomycetous fungus Flammulina velutipes.

    Science.gov (United States)

    Shi, Liang; Chen, Dongdong; Xu, Chao; Ren, Ang; Yu, Hanshou; Zhao, Mingwen

    2017-07-11

    Flammulina velutipes is a well-known edible mushroom cultivated all over the world. However, because of the low transformation frequency, the expensive instruments required, and the complicated, time-consuming procedures necessary, there is insufficient genetic research on F. velutipes. In this study, we report a liposome-mediated transformation (LMT) system for the genetic transformation of F. velutipes. Using the LMT system, we obtained 82 ± 4 stable F. velutipes transformants per 10 5 protoplasts, which is a clear increase in transformation frequency compared to the other methods used. We were able to detect the expression of an EGFP reporter gene in the F. velutipes transformants using fluorescence imaging assays. Furthermore, we used this method to transfer the laccase gene into F. velutipes and found that the transcriptional level and enzymatic activity increased in these transformants. Mitotic stability analysis showed that all of the selected transformants remained mitotically stable, even after five successive rounds of sub-culturing. These results demonstrate a new transgenic approach that will facilitate F. velutipes research.

  19. 75 FR 57191 - Compliance With Interstate Motor Carrier Noise Emission Standards: Exhaust Systems

    Science.gov (United States)

    2010-09-20

    ... 28, 1975, the Federal Highway Administration (FHWA)'s Bureau of Motor Carrier Safety published in the... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration 49 CFR Part 325 [Docket...: Exhaust Systems AGENCY: Federal Motor Carrier Safety Administration, DOT. ACTION: Direct final rule...

  20. Aerosolized liposomes with dipalmitoyl phosphatidylcholine enhance pulmonary absorption of encapsulated insulin compared with co-administered insulin.

    Science.gov (United States)

    Chono, Sumio; Togami, Kohei; Itagaki, Shirou

    2017-11-01

    We have previously shown that aerosolized liposomes with dipalmitoyl phosphatidylcholine (DPPC) enhance the pulmonary absorption of encapsulated insulin. In this study, we aimed to compare insulin encapsulated into the liposomes versus co-administration of empty liposomes and unencapsulated free insulin, where the DPCC liposomes would serve as absorption enhancer. The present study provides the useful information for development of noninvasive treatment of diabetes. Co-administration of empty DPPC liposomes and unencapsulated free insulin was investigated in vivo to assess the potential enhancement in protein pulmonary absorption. Co-administration was compared to DPPC liposomes encapsulating insulin, and free insulin. DPPC liposomes enhanced the pulmonary absorption of unencapsulated free insulin; however, the enhancing effect was lower than that of the DPPC liposomes encapsulating insulin. The mechanism of the pulmonary absorption of unencapsulated free insulin by DPPC liposomes involved the opening of epithelial cell space in alveolar mucosa, and not mucosal cell damage, similar to that of the DPPC liposomes encapsulating insulin. In an in vitro stability test, insulin in the alveolar mucus layer that covers epithelial cells was stable. These findings suggest that, although unencapsulated free insulin spreads throughout the alveolar mucus layer, the concentration of insulin released near the absorption surface is increased by the encapsulation of insulin into DPPC liposomes and the absorption efficiency is also increased. We revealed that the encapsulation of insulin into DPPC liposomes is more effective for pulmonary insulin absorption than co-administration of DPPC liposomes and unencapsulated free insulin.

  1. Complement activation-related pseudoallergy in dogs following intravenous administration of a liposomal formulation of meglumine antimoniate

    Directory of Open Access Journals (Sweden)

    Raul R. Ribeiro

    2013-08-01

    Full Text Available The increasing use of nanotechnologies in advanced therapies has allowed the observation of specific adverse reactions related to nanostructures. The toxicity of a novel liposome formulation of meglumine antimoniate in dogs with visceral leishmaniasis after single dose has been investigated. Groups of 12 animals received by the intravenous route a single dose of liposomal meglumine antimoniate (group I [GI], 6.5 mg Sb/kg, empty liposomes (GII or isotonic saline (GIII. Evaluation of hematological and biochemical parameters showed no significant changes 4 days after administration. No undesired effects were registered in the GIII. However, adverse reactions were observed in 67.7% of dogs from both groups that received liposomal formulations. The side effects began moments after bolus administration and disappeared during the first 15 minutes after treatment. Prostation, sialorrhea and defecation were the most frequent clinical signs, registered in 33.3% and 41.6 % of animals from the groups GI and GII, respectively. Tachypnea, mydriasis, miosis, vomiting and cyanosis were also registered in both groups. The adverse reactions observed in this study were attributed to the activation of the complement system by lipid vesicles in a phenomenon known as Complement Activation-Related Pseudoallergy (CARPA. The influence of the physical-chemical characteristics of liposomal formulation in the triggering of CARPA is discussed.

  2. Contribution à la formulation et à l'évaluation de liposomes d'ATP

    OpenAIRE

    Vincourt-Vitse, Véronique,

    2012-01-01

    ATP liposome incorporating hepatic ligands may contribute to improve the energetic status of the liver graft. In a first phase of development, it has been emphasized the great need of stabilizing the liposome (i) and of validating a cellular model with an altered energetic status in order to test the formulations of interest. To provide a stable liposomal preparation, different strategies have been carried out to freeze-dry liposome with or without ATP. Sucrose and trehalose better stabilize ...

  3. pH-sensitive liposomes containing polymerized phosphatidylethanolamine and fatty acid.

    Science.gov (United States)

    Choi, M J; Han, H S; Kim, H

    1992-11-01

    With the ultimate aim of targeting cancer drugs to malignant tissues, liposomes containing polymeric phosphatidylethanolamine and a fatty acid were prepared. For this purpose diacetylenic phosphatidylethanolamine (DAPE), a phosphatidylethanolamine containing diacetylene, was synthesized. Liposomes containing DAPE, fatty acid, and either phosphatidylethanolamine (PE) or phosphatidylethanolamine-beta-oleoyl-gamma-palmitoyl (POPE) were then prepared. Polymerization of DAPE was effected by UV illumination. The polymeric liposomes so obtained were stable at physiological pH but became leaky below pH 6.5. Of various compositions studied, the greatest pH-sensitivity was found with liposomes composed of 35 mol% DAPE, 35 mol% POPE, and 30 mol% saturated fatty acid. The presence of blood plasma albumin decreased vesicle stability while apolipoprotein A-I (apo A-I) had the opposite effect and plasma as a whole had a slightly stabilizing effect.

  4. Current Demands for Food-Approved Liposome Nanoparticles in Food and Safety Sector

    Directory of Open Access Journals (Sweden)

    Shruti Shukla

    2017-12-01

    Full Text Available Safety of food is a noteworthy issue for consumers and the food industry. A number of complex challenges associated with food engineering and food industries, including quality food production and safety of the food through effective and feasible means can be explained by nanotechnology. However, nanoparticles have unique physicochemical properties compared to normal macroparticles of the same composition and thus could interact with living system in surprising ways to induce toxicity. Further, few toxicological/safety assessments have been performed on nanoparticles, thereby necessitating further research on oral exposure risk prior to their application to food. Liposome nanoparticles are viewed as attractive novel materials by the food and medical industries. For example, nanoencapsulation of bioactive food compounds is an emerging application of nanotechnology. In several food industrial practices, liposome nanoparticles have been utilized to improve flavoring and nutritional properties of food, and they have been examined for their capacity to encapsulate natural metabolites that may help to protect the food from spoilage and degradation. This review focuses on ongoing advancements in the application of liposomes for food and pharma sector.

  5. Combination of TRAIL and actinomycin D liposomes enhances antitumor effect in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Guo LG

    2012-03-01

    Full Text Available Liangran Guo1,2,4, Li Fan1,2, Jinfeng Ren1,2, Zhiqing Pang1,2, Yulong Ren1,2, Jingwei Li1,2, Ziyi Wen1,3, Yong Qian1,2, Lin Zhang1,2, Hang Ma4, Xinguo Jiang1,2 1School of Pharmacy, Fudan University, Zhangheng Road, Shanghai, 2Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, Shanghai, 3School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China; 4College of Pharmacy, University of Rhode Island, RI, USAAbstract: The intractability of non-small cell lung cancer (NSCLC to multimodality treatments plays a large part in its extremely poor prognosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL is a promising cytokine for selective induction of apoptosis in cancer cells; however, many NSCLC cell lines are resistant to TRAIL-induced apoptosis. The therapeutic effect can be restored by treatments combining TRAIL with chemotherapeutic agents. Actinomycin D (ActD can sensitize NSCLC cells to TRAIL-induced apoptosis by upregulation of death receptor 4 (DR4 or 5 (DR5. However, the use of ActD has significant drawbacks due to the side effects that result from its nonspecific biodistribution in vivo. In addition, the short half-life of TRAIL in serum also limits the antitumor effect of treatments combining TRAIL and ActD. In this study, we designed a combination treatment of long-circulating TRAIL liposomes and ActD liposomes with the aim of resolving these problems. The combination of TRAIL liposomes and ActD liposomes had a synergistic cytotoxic effect against A-549 cells. The mechanism behind this combination treatment includes both increased expression of DR5 and caspase activation. Moreover, systemic administration of the combination of TRAIL liposomes and ActD liposomes suppressed both tumor formation and growth of established subcutaneous NSCLC xenografts in nude mice, inducing apoptosis without causing significant general toxicity. These results provide preclinical proof

  6. Modeling Drug-Carrier Interaction in the Drug Release from Nanocarriers

    Directory of Open Access Journals (Sweden)

    Like Zeng

    2011-01-01

    Full Text Available Numerous nanocarriers of various compositions and geometries have been developed for the delivery and release of therapeutic and imaging agents. Due to the high specific surface areas of nanocarriers, different mechanisms such as ion pairing and hydrophobic interaction need to be explored for achieving sustained release. Recently, we developed a three-parameter model that considers reversible drug-carrier interaction and first-order drug release from liposomes. A closed-form analytical solution was obtained. Here, we further explore the ability of the model to capture the release of bioactive molecules such as drugs and growth factors from various nanocarriers. A parameter study demonstrates that the model is capable of resembling major categories of drug release kinetics. We further fit the model to 60 sets of experimental data from various drug release systems, including nanoparticles, hollow particles, fibers, and hollow fibers. Additionally, bootstrapping is used to evaluate the accuracy of parameter determination and validate the model in selected cases. The simplicity and universality of the model and the clear physical meanings of each model parameter render the model useful for the design and development of new drug delivery systems.

  7. Photophysical properties and localization of chlorins substituted with methoxy groups, hydroxyl groups and alkyl chains in liposome-like cellular membrane

    Energy Technology Data Exchange (ETDEWEB)

    Al-Omari, S [Department of Physics, Hashemite University, Zarqa 13115 (Jordan)

    2007-06-01

    Some of the photophysical properties (stationary absorbance and fluorescence, fluorescence decay times and singlet oxygen quantum yields) of chlorins substituted with methoxy groups, hydroxyl groups and hydrocarbonic chains were studied in ethanol and dipalmitoyl-phosphatidylcholine (DPPC) liposomes using steady-state and time-resolved fluorescence spectroscopies. The photophysical behaviors of the chlorins in liposomes like cellular membrane were compared with those obtained from chlorin-liposome systems delivered to Jurkat cells in order to select potent photosensitizers for the photodynamic treatment of cancer. The localization of the studied chlorins inside liposomes was found to depend strongly on the substituents of chlorins. Absorption spectra of chlorins embedded in DPPC-liposomes have been recorded in the temperature range of 20-70 deg. C. It is demonstrated that the location of the chlorin molecules depends on the phase state of the phospholipids. These observations are confirmed by the fluorescence lifetimes, singlet oxygen lifetimes and singlet oxygen quantum yields results.

  8. Prednisolone phosphate-containing TRX-20 liposomes inhibit cytokine and chemokine production in human fibroblast-like synovial cells: a novel approach to rheumatoid arthritis therapy.

    Science.gov (United States)

    Harigai, Takashi; Hagiwara, Hitomi; Ogawa, Yumi; Ishizuka, Takanobu; Kaneda, Shinichi; Kimura, Junji

    2007-01-01

    To evaluate the potential of using prednisolone phosphate (PSLP)-containing 3,5-dipentadecyloxybenzamidine hydrochloride (TRX-20) liposomes to treat rheumatoid arthritis (RA), we examined their ability to bind human fibroblast-like synovial (HFLS) cells and their effects in these cells. To test for binding, Lissamine rhodamine B-1, 2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (rhodamine)-labelled PSLP-containing TRX-20 liposomes were added to HFLS cells, and the fluorescence intensity of the rhodamine bound to the cells was evaluated. Rhodamine-labelled PSLP-containing liposomes without TRX-20 were used as a negative control. To evaluate the uptake of liposomes by the HFLS cells, we used TRX-20 liposomes containing 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) and p-xylene-bis-pyridinium bromide (DPX), and observed the cells by fluorescence microscopy. The effects of the PSLP in TRX-20 liposomes on HFLS cells were assessed by the inhibition of the production of two inflammatory cytokines (interleukin 6 and granulocyte macrophage colony-stimulating factor) and one inflammatory chemokine (interleukin 8). The interaction of the PSLP-containing TRX-20 liposomes with HFLS cells was approximately 40 times greater than that of PSLP-containing liposomes without TRX-20. PSLP-containing TRX-20 liposomes bound to HFLS cells primarily via chondroitin sulfate. TRX-20 liposomes taken up by the cell were localized to acidic compartments. Furthermore, the PSLP-containing TRX-20 liposomes inhibited the production of the inflammatory cytokines and the chemokine more effectively than did the PSLP-containing liposomes without TRX-20. These results indicate that PSLP-containing TRX-20 liposomes show promise as a novel drug delivery system that could enhance the clinical use of glucocorticoids for treating RA.

  9. Innovative bionanocomposite films of edible proteins containing liposome-encapsulated nisin and halloysite nanoclay.

    Science.gov (United States)

    Boelter, Juliana Ferreira; Brandelli, Adriano

    2016-09-01

    Films and coatings based on natural polymers have gained increased interest for food packaging applications. In this work, halloysite and phosphatidylcholine liposomes encapsulating nisin were used to develop nanocomposite films of gelatin and casein. Liposomes prepared with either soybean lecithin or Phospholipon(®) showed particle size ranging from 124 to 178nm and high entrapment efficiency (94-100%). Considering their stability, Phospholipon(®) liposomes with 1.0mg/ml nisin were selected for incorporation into nanocomposite films containing 0.5g/l halloysite. The films presented antimicrobial activity against Listeria monocytogenes, Clostridium perfringens and Bacillus cereus. Scanning electron microscopy revealed that the films had a smooth surface, but showed increased roughness with addition of liposomes and halloysite. Casein films were thinner and slightly yellowish, less rigid and very elastic as compared with gelatin films. Thermogravimetric analysis showed a decrease of the degradation temperature for casein films added with liposomes. The glass transition temperature decreased with addition of liposomes and halloysite. Gelatin and casein films containing nisin-loaded liposomes and halloysite represent an interesting alternative for development of active food packaging. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Intracellular delivery of oligonucleotides in Helicobacter pylori by fusogenic liposomes in the presence of gastric mucus.

    Science.gov (United States)

    Santos, Rita S; Dakwar, George R; Zagato, Elisa; Brans, Toon; Figueiredo, Céu; Raemdonck, Koen; Azevedo, Nuno F; De Smedt, Stefaan C; Braeckmans, Kevin

    2017-09-01

    The rising antimicrobial resistance contributes to 25000 annual deaths in Europe. This threat to the public health can only be tackled if novel antimicrobials are developed, combined with a more precise use of the currently available antibiotics through the implementation of fast, specific, diagnostic methods. Nucleic acid mimics (NAMs) that are able to hybridize intracellular bacterial RNA have the potential to become such a new class of antimicrobials and additionally could serve as specific detection probes. However, an essential requirement is that these NAMs should be delivered into the bacterial cytoplasm, which is a particular challenge given the fact that they are charged macromolecules. We consider these delivery challenges in relation to the gastric pathogen Helicobacter pylori, the most frequent chronic infection worldwide. In particular, we evaluate if cationic fusogenic liposomes are suitable carriers to deliver NAMs across the gastric mucus barrier and the bacterial envelope. Our study shows that DOTAP-DOPE liposomes post-PEGylated with DSPE-PEG (DSPE Lpx) can indeed successfully deliver NAMs into Helicobacter pylori, while offering protection to the NAMs from binding and inactivation in gastric mucus isolated from pigs. DSPE Lpx thus offer exciting new possibilities for in vivo diagnosis and treatment of Helicobacter pylori infections. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Near-infrared-fluorescence imaging of lymph nodes by using liposomally formulated indocyanine green derivatives.

    Science.gov (United States)

    Toyota, Taro; Fujito, Hiromichi; Suganami, Akiko; Ouchi, Tomoki; Ooishi, Aki; Aoki, Akira; Onoue, Kazutaka; Muraki, Yutaka; Madono, Tomoyuki; Fujinami, Masanori; Tamura, Yutaka; Hayashi, Hideki

    2014-01-15

    Liposomally formulated indocyanine green (LP-ICG) has drawn much attention as a highly sensitive near-infrared (NIR)-fluorescence probe for tumors or lymph nodes in vivo. We synthesized ICG derivatives tagged with alkyl chains (ICG-Cn), and we examined NIR-fluorescence imaging for lymph nodes in the lower extremities of mice by using liposomally formulated ICG-Cn (LP-ICG-Cn) as well as conventional liposomally formulated ICG (LP-ICG) and ICG. Analysis with a noninvasive preclinical NIR-fluorescence imaging system revealed that LP-ICG-Cn accumulates in only the popliteal lymph node 1h after injection into the footpad, whereas LP-ICG and ICG accumulate in the popliteal lymph node and other organs like the liver. This result indicates that LP-ICG-Cn is a useful NIR-fluorescence probe for noninvasive in vivo bioimaging, especially for the sentinel lymph node. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Effects of 5-nitro-2-furaldehyde on the radiation damage of liposomes

    International Nuclear Information System (INIS)

    Kuropteva, Z.V.; Sprinz, H.; Schaefer, H.; Winkler, E.

    1986-01-01

    By means of 1 H-NMR spectroscopy the influence of 5-nitro-2-furaldehyde (NF) on the permeation of Eu 3+ ions into irradiated liposomes of egg yolk lecithin was examined. In the presence of NF there was an increase in the permeability of irradiated liposomes. The damage of the liposomes was quantified spectrophotometrically in terms of diene conjugation. (author)

  13. Simultant encapsulation of vitamin C and beta-carotene in sesame (Sesamum indicum l.) liposomes

    Science.gov (United States)

    Hudiyanti, D.; Fawrin, H.; Siahaan, P.

    2018-04-01

    In this study sesame liposomes were used to encapsulate both vitamin C and beta-carotene simultaneously. Liposomes were prepared with addition of cholesterol. The encapsulation efficiency (EE) of sesame liposomes for vitamin C in the present of beta-carotene was 77%. The addition of cholesterol increased the encapsulation efficiency. The highest encapsulation efficiency was 89% obtained in liposomes with 10% and 20% cholesterol. Contrary to that, the highest beta-carotene encapsulation efficiency of 78%, was found in the sesame liposomes prepared without the added cholesterol. Results showed that sesame liposomes can be used to encapsulate beta-carotene and vitamin C simultaneously. When beta-carotene and vitamin C were encapsulated concurrently, cholesterol intensified the efficiency of vitamin C encapsulation on the contrary it diminished the efficiency of beta-carotene encapsulation.

  14. Mechanisms of reduction of antitumor drug toxicity by liposome encapsulation

    Energy Technology Data Exchange (ETDEWEB)

    Rahman, Y. E.; Hanson, W. R.; Bharucha, J.; Ainsworth, E. J.; Jaroslow, B.

    1977-01-01

    The antitumor drug Actinomycin D is effective against the growth of some human solid tumors but its use is limited by its extreme toxicity. The development of a method of administering Act. D to reduce its systemic toxicity by incorporating the drug within liposomes reduced its toxicity but its tumoricidal activity was retained.

  15. The Physical Characterization of Liposome Salicylic Acid Using Transmission Electron Microscope

    International Nuclear Information System (INIS)

    Elman Panjaitan

    2008-01-01

    The physical characterization of liposome, formulated from salicylic acid using thin film hydration methods with cholesterol and soybean lecithin, has been done. The formula was characterized by optical microscopes and Transmission Electron Microscope (TEM). The observation result shows that the salicylic acid can be formulated to liposomes. Soybean lecithin combined with cholesterol (600 mg : 20 mg) was the best formula and the liposome was spherical vesicle like with dimension about 70 nm unit 800 nm. (author)

  16. Adaptive Disturbance Rejection Control for Automatic Carrier Landing System

    Directory of Open Access Journals (Sweden)

    Xin Wang

    2016-01-01

    Full Text Available An adaptive disturbance rejection algorithm is proposed for carrier landing system in the final-approach. The carrier-based aircraft dynamics and the linearized longitudinal model under turbulence conditions in the final-approach are analyzed. A stable adaptive control scheme is developed based on LDU decomposition of the high-frequency gain matrix, which ensures closed-loop stability and asymptotic output tracking. Finally, simulation studies of a linearized longitudinal-directional dynamics model are conducted to demonstrate the performance of the adaptive scheme.

  17. Dynamical and structural properties of lipid membranes in relation to liposomal drug delivery systems

    DEFF Research Database (Denmark)

    Jørgensen, Kent; Høyrup, Lise Pernille Kristine; Pedersen, Tina B.

    2001-01-01

    The structural and dynamical properties of DPPC liposomes containing lipopolymers (PEG-lipids) and charged DPPS lipids have been,studied in relation to the lipid membrane interaction of enzymes and peptides. The results suggest that both the lipid membrane structure and dynamics and in particular...

  18. Liposomal packaging generates Wnt protein with in vivo biological activity.

    Directory of Open Access Journals (Sweden)

    Nathan T Morrell

    2008-08-01

    Full Text Available Wnt signals exercise strong cell-biological and regenerative effects of considerable therapeutic value. There are, however, no specific Wnt agonists and no method for in vivo delivery of purified Wnt proteins. Wnts contain lipid adducts that are required for activity and we exploited this lipophilicity by packaging purified Wnt3a protein into lipid vesicles. Rather than being encapsulated, Wnts are tethered to the liposomal surface, where they enhance and sustain Wnt signaling in vitro. Molecules that effectively antagonize soluble Wnt3a protein but are ineffective against the Wnt3a signal presented by a cell in a paracrine or autocrine manner are also unable to block liposomal Wnt3a activity, suggesting that liposomal packaging mimics the biological state of active Wnts. When delivered subcutaneously, Wnt3a liposomes induce hair follicle neogenesis, demonstrating their robust biological activity in a regenerative context.

  19. A Liposomal Formulation Able to Incorporate a High Content of Paclitaxel and Exert Promising Anticancer Effect

    Directory of Open Access Journals (Sweden)

    Pei Kan

    2011-01-01

    Full Text Available A liposome formulation for paclitaxel was developed in this study. The liposomes, composed of naturally unsaturated and hydrogenated phosphatidylcholines, with significant phase transition temperature difference, were prepared and characterized. The liposomes exhibited a high content of paclitaxel, which was incorporated within the segregated microdomains coexisting on phospholipid bilayer of liposomes. As much as 15% paclitaxel to phospholipid molar ratio were attained without precipitates observed during preparation. In addition, the liposomes remained stable in liquid form at 4∘C for at least 6 months. The special composition of liposomal membrane which could reduce paclitaxel aggregation could account for such a capacity and stability. The cytotoxicity of prepared paclitaxel liposomes on the colon cancer C-26 cell culture was comparable to Taxol. Acute toxicity test revealed that LD50 for intravenous bolus injection in mice exceeded by 40 mg/kg. In antitumor efficacy study, the prepared liposomal paclitaxel demonstrated the increase in the efficacy against human cancer in animal model. Taken together, the novel formulated liposomes can incorporate high content of paclitaxel, remaining stable for long-term storage. These animal data also demonstrate that the liposomal paclitaxel is promising for further clinical use.

  20. Transport of Glial Cell Line-Derived Neurotrophic Factor into Liposomes across the Blood-Brain Barrier: In Vitro and in Vivo Studies

    Directory of Open Access Journals (Sweden)

    Shaoling Wu

    2014-02-01

    Full Text Available Glial cell line-derived neurotrophic factor (GDNF was encapsulated into liposomes in order to protect it from enzyme degradation in vivo and promote its permeability across the blood-brain barrier (BBB. In this study, GDNF conventional liposomes (GDNF-L and GDNF target sterically stabilized liposomes (GDNF-SSL-T were prepared. The average size of liposomes was below 90 nm. A primary model of BBB was established and evaluated by transendothelial electrical resistance (TEER and permeability. This BBB model was employed to study the permeability of GDNF liposomes in vitro. The results indicated that the liposomes could enhance transport of GDNF across the BBB and GDNF-SSL-T had achieved the best transport efficacy. The distribution of GDNF liposomes was studied in vivo. Free GDNF and GDNF-L were eliminated rapidly in the circulation. GDNF-SSL-T has a prolonged circulation time in the blood and favorable brain delivery. The values of the area under the curve (AUC(0–1 h in the brain of GDNF-SSL-T was 8.1 times and 6.8 times more than that of free GDNF and GDNF-L, respectively. These results showed that GDNF-SSL-T realized the aim of targeted delivery of therapeutic proteins to central nervous system.

  1. The clearance of liposomes administered by the intramuscular route

    International Nuclear Information System (INIS)

    Arrowsmith, M.; Mills, S.N.

    1982-01-01

    Iodine 131-labelled lecithin was used to label liposomes entrapping cortisone-21-palmitate. The lecithin was injected into the fascia latae muscles of rabbits and the percentage of the initial dose remaining at certain time intervals was calculated from gamma camera image data. Release from the intramuscular site occurs by diffusion from intact liposomes. (U.K.)

  2. Sonoporation enhances liposome accumulation and penetration in tumors with low EPR.

    Science.gov (United States)

    Theek, Benjamin; Baues, Maike; Ojha, Tarun; Möckel, Diana; Veettil, Seena Koyadan; Steitz, Julia; van Bloois, Louis; Storm, Gert; Kiessling, Fabian; Lammers, Twan

    2016-06-10

    The Enhanced Permeability and Retention (EPR) effect is a highly variable phenomenon. To enhance EPR-mediated passive drug targeting to tumors, several different pharmacological and physical strategies have been evaluated over the years, including e.g. TNFα-treatment, vascular normalization, hyperthermia and radiotherapy. Here, we systematically investigated the impact of sonoporation, i.e. the combination of ultrasound (US) and microbubbles (MB), on the tumor accumulation and penetration of liposomes. Two different MB formulations were employed, and their ability to enhance liposome accumulation and penetration was evaluated in two different tumor models, which are both characterized by relatively low levels of EPR (i.e. highly cellular A431 epidermoid xenografts and highly stromal BxPC-3 pancreatic carcinoma xenografts). The liposomes were labeled with two different fluorophores, enabling in vivo computed tomography/fluorescence molecular tomography (CT-FMT) and ex vivo two-photon laser scanning microscopy (TPLSM). In both models, in spite of relatively high inter- and intra-individual variability, a trend towards improved liposome accumulation and penetration was observed. In treated tumors, liposome concentrations were up to twice as high as in untreated tumors, and sonoporation enhanced the ability of liposomes to extravasate out of the blood vessels into the tumor interstitium. These findings indicate that sonoporation may be a useful strategy for improving drug targeting to tumors with low EPR. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Surface modified liposomes by mannosylated conjugates anchored via the adamantyl moiety in the lipid bilayer.

    Science.gov (United States)

    Stimac, Adela; Segota, Suzana; Dutour Sikirić, Maja; Ribić, Rosana; Frkanec, Leo; Svetličić, Vesna; Tomić, Srđanka; Vranešić, Branka; Frkanec, Ruža

    2012-09-01

    The aim of the present study was to encapsulate mannosylated 1-aminoadamantane and mannosylated adamantyltripeptides, namely [(2R)-N-(adamant-1-yl)-3-(α,β-d-mannopyranosyloxy)-2-methylpropanamide and (2R)-N-[3-(α-d-mannopyranosyloxy)-2-methylpropanoyl]-d,l-(adamant-2-yl)glycyl-l-alanyl-d-isoglutamine] in liposomes. The characterization of liposomes, size and surface morphology was performed using dynamic light scattering (DLS) and atomic force microscopy (AFM). The results have revealed that the encapsulation of examined compounds changes the size and surface of liposomes. After the concanavalin A (ConA) was added to the liposome preparation, increase in liposome size and their aggregation has been observed. The enlargement of liposomes was ascribed to the specific binding of the ConA to the mannose present on the surface of the prepared liposomes. Thus, it has been shown that the adamantyl moiety from mannosylated 1-aminoadamantane and mannosylated adamantyltripeptides can be used as an anchor in the lipid bilayer for carbohydrate moiety exposed on the liposome surface. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators

    DEFF Research Database (Denmark)

    Schmidt, Signe Tandrup; Foged, Camilla; Korsholm, Karen Smith

    2016-01-01

    be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode......The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens...... of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the specific PRR expression profile of the target APCs. Here, we review state-of-the-art formulation approaches employed for the inclusion of immunostimulators and subunit...

  5. Liposomal Antioxidants for Protection against Oxidant-Induced Damage

    Directory of Open Access Journals (Sweden)

    Zacharias E. Suntres

    2011-01-01

    Full Text Available Reactive oxygen species (ROS, including superoxide anion, hydrogen peroxide, and hydroxyl radical, can be formed as normal products of aerobic metabolism and can be produced at elevated rates under pathophysiological conditions. Overproduction and/or insufficient removal of ROS result in significant damage to cell structure and functions. In vitro studies showed that antioxidants, when applied directly and at relatively high concentrations to cellular systems, are effective in conferring protection against the damaging actions of ROS, but results from animal and human studies showed that several antioxidants provide only modest benefit and even possible harm. Antioxidants have yet to be rendered into reliable and safe therapies because of their poor solubility, inability to cross membrane barriers, extensive first-pass metabolism, and rapid clearance from cells. There is considerable interest towards the development of drug-delivery systems that would result in the selective delivery of antioxidants to tissues in sufficient concentrations to ameliorate oxidant-induced tissue injuries. Liposomes are biocompatible, biodegradable, and nontoxic artificial phospholipid vesicles that offer the possibility of carrying hydrophilic, hydrophobic, and amphiphilic molecules. This paper focus on the use of liposomes for the delivery of antioxidants in the prevention or treatment of pathological conditions related to oxidative stress.

  6. Development and Characterization of Liposomal Doxorubicin Hydrochloride with Palm Oil

    Directory of Open Access Journals (Sweden)

    Bahareh Sabeti

    2014-01-01

    Full Text Available The usage of natural products in pharmaceuticals has steadily seen improvements over the last decade, and this study focuses on the utilization of palm oil in formulating liposomal doxorubicin (Dox. The liposomal form of Dox generally minimizes toxicity and enhances target delivery actions. Taking into account the antiproliferative and antioxidant properties of palm oil, the aim of this study is to design and characterize a new liposomal Dox by replacing phosphatidylcholine with 5% and 10% palm oil content. Liposomes were formed using the freeze_thaw method, and Dox was loaded through pH gradient technique and characterized through in vitro and ex vivo terms. Based on TEM images, large lamellar vesicles (LUV were formed, with sizes of 438 and 453 nm, having polydispersity index of 0.21 ± 0.8 and 0.22 ± 1.3 and zeta potentials of about −31 and −32 mV, respectively. In both formulations, the entrapment efficiency was about 99%, and whole Dox was released through 96 hours in PBS (pH = 7.4 at 37°C. Comparing cytotoxicity and cellular uptake of LUV with CaelyxR on MCF7 and MDA-MBA 231 breast cancer cell lines indicated suitable uptake and lower IC50 of the prepared liposomes.

  7. Application of Liposomes in Treatment of Rheumatoid Arthritis: Quo Vadis

    Directory of Open Access Journals (Sweden)

    Bhupinder Kapoor

    2014-01-01

    Full Text Available The most common treatments for rheumatoid arthritis include nonsteroidal anti-inflammatory drugs (NSAIDs, corticosteroids, disease modifying antirheumatic drugs (DMARDs, and some biological agents. However, none of the treatments available is able to achieve the ultimate goal of treatment, that is, drug-free remission. This limitation has shifted the focus of treatment to delivery strategies with an ability to deliver the drugs into the synovial cavity in the proper dosage while mitigating side effects to other tissues. A number of approaches like microemulsions, microspheres, liposomes, microballoons, cocrystals, nanoemulsions, dendrimers, microsponges, and so forth, have been used for intrasynovial delivery of these drugs. Amongst these, liposomes have proven to be very effective for retaining the drug in the synovial cavity by virtue of their size and chemical composition. The fast clearance of intra-synovially administered drugs can be overcome by use of liposomes leading to increased uptake of drugs by the target synovial cells, which in turn reduces the exposure of nontarget sites and eliminates most of the undesirable effects associated with therapy. This review focuses on the use of liposomes in treatment of rheumatoid arthritis and summarizes data relating to the liposome formulations of various drugs. It also discusses emerging trends of this promising technology.

  8. Biological Atomic Force Microscopy for Imaging Gold-Labeled Liposomes on Human Coronary Artery Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Ana-María Zaske

    2013-01-01

    Full Text Available Although atomic force microscopy (AFM has been used extensively to characterize cell membrane structure and cellular processes such as endocytosis and exocytosis, the corrugated surface of the cell membrane hinders the visualization of extracellular entities, such as liposomes, that may interact with the cell. To overcome this barrier, we used 90 nm nanogold particles to label FITC liposomes and monitor their endocytosis on human coronary artery endothelial cells (HCAECs in vitro. We were able to study the internalization process of gold-coupled liposomes on endothelial cells, by using AFM. We found that the gold-liposomes attached to the HCAEC cell membrane during the first 15–30 min of incubation, liposome cell internalization occurred from 30 to 60 min, and most of the gold-labeled liposomes had invaginated after 2 hr of incubation. Liposomal uptake took place most commonly at the periphery of the nuclear zone. Dynasore monohydrate, an inhibitor of endocytosis, obstructed the internalization of the gold-liposomes. This study showed the versatility of the AFM technique, combined with fluorescent microscopy, for investigating liposome uptake by endothelial cells. The 90 nm colloidal gold nanoparticles proved to be a noninvasive contrast agent that efficiently improves AFM imaging during the investigation of biological nanoprocesses.

  9. Undulating tubular liposomes through incorporation of a synthetic skin ceramide into phospholipid bilayers.

    Science.gov (United States)

    Xu, Peng; Tan, Grace; Zhou, Jia; He, Jibao; Lawson, Louise B; McPherson, Gary L; John, Vijay T

    2009-09-15

    Nonspherical liposomes were prepared by doping L-alpha-phosphatidylcholine (PC) with ceramide VI (a skin lipid). Cryo-transmission electron microscopy shows the liposome shape changing from spherical to an undulating tubular morphology, when the amount of ceramide VI is increased. The formation of tubular liposomes is energetically favorable and is attributed to the association of ceramide VI with PC creating regions of lower curvature. Since ceramides are the major component of skin lipids in the stratum corneum, tubular liposomes containing ceramide may potentially serve as self-enhanced nanocarriers for transdermal delivery.

  10. Efficacy of Liposomal Bupivacaine Infiltration on the Management of Total Knee Arthroplasty.

    Science.gov (United States)

    Sakamoto, Bryan; Keiser, Shelly; Meldrum, Russell; Harker, Gene; Freese, Andrew

    2017-01-01

    Liposomal bupivacaine is a novel extended-duration anesthetic that has recently been used for local infiltration in total knee arthroplasty (TKA). Athough liposomal bupivacaine is widely used, it is unknown if the benefits justify the cost in the veteran population at our institution. To evaluate a change in practice: the effect of local infiltration of liposomal bupivacaine on perioperative outcomes in patients undergoing primary TKA. A retrospective cohort study was conducted among patients who underwent primary TKA at a Veterans Affairs Medical Center before (March 3, 2013-March 2, 2014) and after (March 3, 2014-March 2, 2015) the implementation of liposomal bupivacaine for local infiltration in TKA. Drug utilization evaluation of liposomal bupivacaine for local infiltration in TKA. Use of opioids after discharge from the postanesthesia care unit. Among 199 patients, those who received liposomal bupivacaine after primary TKA (mean [SD] age, 65.3 [6.9] years; 93 males and 5 females) had a reduced median opioid use in the first 24 hours after surgery compared with those who did not receive liposomal bupivacaine (mean [SD] age, 64.9 [8.4] years; 95 males and 6 females; [intravenous morphine equivalents, 12.50 vs 22.50 mg; P = .001]). The use of patient-controlled analgesia was also reduced among patients who received liposomal bupivacaine vs those who did not (49 vs 91; P bupivacaine vs those who did not (4 vs 20; P = .001). The number of patients in the postanesthesia care unit with no pain was improved among those who received liposomal bupivacaine vs those who did not (44 vs 19; P bupivacaine vs those who did not (4.0 [0.0-6.6] vs 5.5 [3.0-7.5]; P = .001), patients who received liposomal bupivacaine had greater median (interquartile range) pain scores 48 hours (5.5 [4.0-7.0] vs 5.0 [3.0-6.0]; P = .01), 72 hours (5.0 [4.0-6.0] vs 4.0 [2.0-6.0]; P = .002), and 96 hours (5.0 [3.0-6.5] vs 4.0 [1.0-5.0]; P = .003) after surgery than those

  11. PMO Delivery System Using Bubble Liposomes and Ultrasound Exposure for Duchenne Muscular Dystrophy Treatment.

    Science.gov (United States)

    Negishi, Yoichi; Ishii, Yuko; Nirasawa, Kei; Sasaki, Eri; Endo-Takahashi, Yoko; Suzuki, Ryo; Maruyama, Kazuo

    2018-01-01

    Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration, caused by nonsense or frameshift mutations in the dystrophin (DMD) gene. Antisense oligonucleotides can be used to induce specific exon skipping; recently, a phosphorodiamidate morpholino oligomer (PMO) has been approved for clinical use in DMD. However, an efficient PMO delivery strategy is required to improve the therapeutic efficacy in DMD patients. We previously developed polyethylene glycol (PEG)-modified liposomes containing ultrasound contrast gas, "Bubble liposomes" (BLs), and found that the combination of BLs with ultrasound exposure is a useful gene delivery tool. Here, we describe an efficient PMO delivery strategy using the combination of BLs and ultrasound exposure to treat muscles in a DMD mouse model (mdx). This ultrasound-mediated BL technique can increase the PMO-mediated exon-skipping efficiency, leading to significantly increased dystrophin expression. Thus, the combination of BLs and ultrasound exposure may be a feasible PMO delivery method to improve therapeutic efficacy and reduce the PMO dosage for DMD treatment.

  12. Systemic study of solvent-assisted active loading of gambogic acid into liposomes and its formulation optimization for improved delivery.

    Science.gov (United States)

    Tang, Wei-Lun; Tang, Wei-Hsin; Szeitz, Andras; Kulkarni, Jayesh; Cullis, Pieter; Li, Shyh-Dar

    2018-06-01

    The solvent-assisted active loading technology (SALT) was developed for encapsulating a water insoluble weak base into the liposomal core in the presence of 5% DMSO. In this study, we further examined the effect of various water miscible solvents in promoting active loading of other types of drugs into liposomes. To achieve complete drug loading, the amount of solvent required must result in complete drug solubilization and membrane permeability enhancement, but must be below the threshold that induces liposomal aggregation or causes bilayer disruption. We then used the SALT to load gambogic acid (GA, an insoluble model drug that shows promising anticancer effect) into liposomes, and optimized the loading gradient and lipid composition to prepare a stable formulation (Lipo-GA) that displayed >95% drug retention after incubation with serum for 3 days. Lipo-GA contained a high drug-to-lipid ratio of 1/5 (w/w) with a mean particle size of ∼75 nm. It also displayed a prolonged circulation half-life (1.5 h vs. 18.6 h) and enhanced antitumor activity in two syngeneic mice models compared to free GA. Particularly, complete tumor regression was observed in the EMT6 tumor model for 14 d with significant inhibition of multiple oncogenes including HIF-1α, VEGF-A, STAT3, BCL-2, and NF-κB. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Biomolecular Interactions of Tannin Isolated from Oenothera gigas with Liposomes.

    Science.gov (United States)

    Sekowski, Szymon; Ionov, Maksim; Dubis, Alina; Mavlyanov, Saidmukhtar; Bryszewska, Maria; Zamaraeva, Maria

    2016-04-01

    We have examined the interaction between hydrolysable tannin 1-O-galloyl-4,6-hexahydroxydiphenoyl-β-D-glucose (OGβDG) with neutral liposomes as a model of cell membranes composed of three lipids: lecithin, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) at different mass ratios. OGβDG in the concentration range 0.5-15 µg/ml (0.4-12 µM) strongly interacts with liposomal membranes by changing their structure, surface charge and fluidity. Used OGβDG molecules decrease and increase the rigidity of hydrophilic surface and hydrophobic parts of liposomes, respectively. At higher concentrations of tannin (>15 µM), liposomes are aggregated. Fourier Transform Infra-Red (FTIR) analysis showed that mainly -OH groups from OGβDG and also PO(2-) groups from phospholipids are responsible for the interaction. Obtained data indicate the importance of membrane lipid composition in interactions between tannins and cells.

  14. Thermoresponsive pegylated bubble liposome nanovectors for efficient siRNA delivery via endosomal escape

    KAUST Repository

    Alamoudi, Kholod

    2017-05-19

    Improving the delivery of siRNA into cancer cells via bubble liposomes. Designing a thermoresponsive pegylated liposome through the introduction of ammonium bicarbonate salt into liposomes so as to control their endosomal escape for gene therapy.A sub-200 nm nanovector was fully characterized and examined for cellular uptake, cytotoxicity, endosomal escape and gene silencing.The siRNA-liposomes were internalized into cancer cells within 5 min and then released siRNAs in the cytosol prior to lysosomal degradation upon external temperature elevation. This was confirmed by confocal bioimaging and gene silencing reaching up to 90% and further demonstrated by the protein inhibition of both target genes.The thermoresponsiveness of ammonium bicarbonate containing liposomes enabled the rapid endosomal escape of the particles and resulted in an efficient gene silencing.

  15. Thermoresponsive pegylated bubble liposome nanovectors for efficient siRNA delivery via endosomal escape

    KAUST Repository

    Alamoudi, Kholod; Martins, Patricia; Croissant, Jonas G.; Patil, Sachin; Omar, Haneen; Khashab, Niveen M.

    2017-01-01

    Improving the delivery of siRNA into cancer cells via bubble liposomes. Designing a thermoresponsive pegylated liposome through the introduction of ammonium bicarbonate salt into liposomes so as to control their endosomal escape for gene therapy.A sub-200 nm nanovector was fully characterized and examined for cellular uptake, cytotoxicity, endosomal escape and gene silencing.The siRNA-liposomes were internalized into cancer cells within 5 min and then released siRNAs in the cytosol prior to lysosomal degradation upon external temperature elevation. This was confirmed by confocal bioimaging and gene silencing reaching up to 90% and further demonstrated by the protein inhibition of both target genes.The thermoresponsiveness of ammonium bicarbonate containing liposomes enabled the rapid endosomal escape of the particles and resulted in an efficient gene silencing.

  16. Wheat germ agglutinin-conjugated liposomes incorporated with cardiolipin to improve neuronal survival in Alzheimer’s disease treatment

    Directory of Open Access Journals (Sweden)

    Kuo YC

    2017-03-01

    Full Text Available Yung-Chih Kuo,1 Che-Yu Lin,1 Jay-Shake Li,2 Yung-I Lou3 1Department of Chemical Engineering, 2Department of Psychology, National Chung Cheng University, Chia-Yi, 3Department of Accounting, Providence University, Taichung, Taiwan, Republic of China Abstract: Curcumin (CRM and nerve growth factor (NGF were entrapped in liposomes (LIP with surface wheat germ agglutinin (WGA to downregulate the phosphorylation of kinases in Alzheimer’s disease (AD therapy. Cardiolipin (CL-conjugated LIP carrying CRM (CRM-CL/LIP and also carrying NGF (NGF-CL/LIP were used with AD models of SK-N-MC cells and Wistar rats after an insult with β-amyloid peptide (Aβ. We found that CRM-CL/LIP inhibited the expression of phosphorylated p38 (p-p38, phosphorylated c-Jun N-terminal kinase (p-JNK, and p-tau protein at serine 202 and prevented neurodegeneration of SK-N-MC cells. In addition, NGF-CL/LIP could enhance the quantities of p-neurotrophic tyrosine kinase receptor type 1 and p-extracellular signal-regulated kinase 5 for neuronal rescue. Moreover, WGA-grafted CRM-CL/LIP and WGA-grafted NGF-CL/LIP significantly improved the permeation of CRM and NGF across the blood–brain barrier, reduced Aβ plaque deposition and the malondialdehyde level, and increased the percentage of normal neurons and cholinergic activity in the hippocampus of AD rats. Based on the marker expressions and in vivo evidence, current LIP carriers can be promising drug delivery systems to protect nervous tissue against Aβ-induced apoptosis in the brain during the clinical management of AD. Keywords: liposome, Alzheimer’s disease, β-amyloid, neurodegeneration, blood–brain barrier, wheat germ agglutinin

  17. Fluorescence studies on gamma irradiated egg lecithin liposomal membrane

    International Nuclear Information System (INIS)

    Pandey, B.N.; Mishra, K.P.

    1998-01-01

    Alterations in structure and organization of sonicated EYL liposomal vesicular membrane after irradiation was investigated by DPH fluorescence probe which is a well known reporter for the environment of hydrophobic interior of membrane. Results of present study have demonstrated that loss of DPH fluorescence in liposomal membrane is linked to free radical mediated structural alterations possibly rigidization in the lipid bilayer

  18. The preparation of Tc-99m labeled liposomes by a cationic SP/DOPE formulation for tumor imaging

    International Nuclear Information System (INIS)

    Yu, M.D.; Hsieh, D.S.; Huang, W.S.

    2002-01-01

    Aim: Liposomes can provide a gene delivery system to be used in the cancer gene therapy. Radiolabeled liposomes can be used in tumor imaging and tumor therapy. A new cationic liposome formulation of sphingosin e (SP) and dioleoylphosphatidylethanolamine (DOPE) was developed and showed very efficient transfection in a wide variety of mammalian cancer cells, including SKOV-3 (human ovarian carcinoma cells), NPC076 (human nasopharyngeal carcinoma cells), and A431 (human epidermoid carcinoma cells) (Kao et al., Oncol Reports. 5:625-629, 1998). The present study is designed and evaluated the labeling and stability of Tc-99m liposomes by SP/DOPE formulation. Material and Methods: A mixture of 8 mg of SP (Sigma Chemical) and 8 mg of DOPE (Sigma Chemical) dissolved in 4 ml absolute ethanol and used as a lipid stock solution (4 mg/ml). In the direct labeling method, taking 0.25 ml (1 mg) stock solution dried under nitrogen gas and then added 1 ml 20 mM HEPES buffer for hydration 8 hours. The remaining stock solution was dried, hydrated 8 hours, and sonicated 10 min to form liposomes for after-loading labeling method (preformed liposomes). The labeling studies included Tc-99m direct labeling (1), Tc-99m HMPAO direct labeling (2), Tc-99m stannous chloride after-loading labeling (3), Tc-99m HMPAO after-loading labeling (4), and Tc-99m pCMVβ DNA inclusion labeling (5). The labeling efficiency (LE) was determined by thin layer chromatography. The labeled liposomes were incubated with fetal bovine serum (FBS) 30 min to evaluate their stability. Results: It is shown that LE (48%) of Tc-99m direct labeling was the highest in the five methods; however, the LE was reduced to 9% (corrected to original LE) after incubating with serum. Tc-99m may be loosely conjugated to the outer surface of the liposomes. The LE (32%) of Tc-99m HMPAO direct labeling was the second; however, LE was most stable when incubating with serum. The LE of the after-loading labeling was not better than that of

  19. Improved stability of highly fluorinated phospholipid-based vesicles in the presence of bile salts.

    Science.gov (United States)

    Gadras, C; Santaella, C; Vierling, P

    1999-01-04

    The stability of fluorinated phospholipid-based vesicles in terms of detergent-induced release of encapsulated carboxyfluorescein has been evaluated. The fluorinated liposomes are substantially more resistant towards the lytic action of sodium taurocholate than conventional DSPC or even DSPC/CH 1/1 liposomes. Concerning structure/permeability relationships, the larger the fluorination degree of the membrane, the higher the resistance of the fluorinated liposomes to their destruction by the detergent. These results show that fluorinated liposomes have a promising potential as drug carrier and delivery systems for oral administration.

  20. Encapsulation of phytosterols and phytosterol esters in liposomes made with soy phospholipids by high pressure homogenization.

    Science.gov (United States)

    Wang, Fan C; Acevedo, Nuria; Marangoni, Alejandro G

    2017-11-15

    Phytosterols and phytosterol esters were encapsulated within large unilamellar liposomes prepared with soy phospholipids using a microfluidizer. The average particle diameter of these liposomal vesicles increased with increasing amounts of encapsulated phytosterols, especially with increasing free sterol content. The phytosterol content, liposomal particle size, and phytosterol encapsulation efficiency started to plateau when liposomes were prepared with MOPS buffer dispersions that contained 50 mg ml -1 soy phospholipid and more than 4% phytosterol blend, suggesting the saturation of phytosterol encapsulation. We proposed an encapsulation mechanism of free sterols and phytosterol esters in liposomes, where free sterols were mainly encapsulated within the lumen of these liposomes as crystals, and sterol esters and some free sterols were incorporated within the phospholipid bilayer of the liposomal membrane. The results from this work could provide the pharmaceutical and nutraceutical industries a practical method to produce loaded liposomes using inexpensive phospholipid mixtures for the delivery of bioactive ingredients.