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Sample records for cationic liposomes loaded

  1. Adjuvant Effect of Cationic Liposomes for Subunit Influenza Vaccine: Influence of Antigen Loading Method, Cholesterol and Immune Modulators

    Directory of Open Access Journals (Sweden)

    Alexander Kros

    2013-07-01

    Full Text Available Cationic liposomes are potential adjuvants for influenza vaccines. In a previous study we reported that among a panel of cationic liposomes loaded with influenza hemagglutinin (HA, DC-Chol:DPPC (1:1 molar ratio liposomes induced the strongest immune response. However, it is not clear whether the cholesterol (Chol backbone or the tertiary amine head group of DC-Chol was responsible for this. Therefore, in the present work we studied the influence of Chol in the lipid bilayer of cationic liposomes. Moreover, we investigated the effect of the HA loading method (adsorption versus encapsulation and the encapsulation of immune modulators in DC-Chol liposomes on the immunogenicity of HA. Liposomes consisting of a neutral lipid (DPPC or Chol and a cationic compound (DC-Chol, DDA, or eDPPC were produced by film hydration-extrusion with/without an encapsulated immune modulator (CpG or imiquimod. The liposomes generally showed comparable size distribution, zeta potential and HA loading. In vitro studies with monocyte-derived human dendritic cells and immunization studies in C57Bl/6 mice showed that: (1 liposome-adsorbed HA is more immunogenic than encapsulated HA; (2 the incorporation of Chol in the bilayer of cationic liposomes enhances their adjuvant effect; and (3 CpG loaded liposomes are more efficient at enhancing HA-specific humoral responses than plain liposomes or Alhydrogel.

  2. siRNA-loaded cationic liposomes for cancer therapy: Development, characterization and efficacy evaluation

    Science.gov (United States)

    Ying, Bo

    Cancer is a major health problem in the United States and many other parts of the world. However, cancer treatment is severely limited by the lack of highly effective cytotoxic agents and selective delivery methods which can serve as the "magic bullet" (first raised by Dr. Paul Ehrlich, the goal of targeting a specific location without causing harm to surrounding tissues or to more distant regions in the body). The revolutionary finding that tumors cannot grow beyond a microscopic size without dedicated blood supply provided a highly effective alternative for the treatment of cancer. Currently, anti-angiogenic therapy and the discovery of RNA interference makes it possible to treat some conditions by silencing disorder-causing genes of targeting cells which are otherwise difficult to eradicate with more conventional therapies. However, before siRNA technology could be widely used as a therapeutic approach, the construct must be efficiently and safely delivered to target cells. Strategies used for siRNA delivery should minimize uptake by phagocytes, enzymatic degradation by nucleases and should be taken up preferentially, if not specifically, by the intended cell population. Kinesin spindle proteins (KSP) are the motor proteins which play critical roles during mitosis. Different from tubulins which are also present in post-mitotic cells, such as axons, KSP is exclusively expressed in mitotic cells, which makes them the ideal target for anti-mitotics. In the present study, we intend to develop, characterize and evaluate a liposome-based delivery system which can deliver KSP siRNA selectively to the tumor vasculature (thus inhibiting angiogenesis, destroying tumor vasculature and eventually, eradicating tumor growth). We first developed ten different liposome preparation types with different compositions of lipids. Next, the capacity for loading siRNA and efficiency of targeting the tumor vascular supply was evaluated using relevant cellular and tumor models

  3. Temoporfin-loaded liposomes

    DEFF Research Database (Denmark)

    Kuntsche, Judith; Freisleben, Ines; Steiniger, Frank;

    2010-01-01

    Temoporfin (mTHPC) is a potent but highly hydrophobic second-generation photosensitizer and has been approved for the palliative treatment of patients with advanced head and neck cancer by photodynamic therapy. Liposome formulations have been evaluated as carrier system for this drug to overcome ...... investigations indicate the presence of micellar structures in addition to vesicles. Lyophilization and reconstitution led to an alteration in the morphology but had overall no distinct influence on the colloidal stability....

  4. Liposome-Loaded Cell Backpacks.

    Science.gov (United States)

    Polak, Roberta; Lim, Rosanna M; Beppu, Marisa M; Pitombo, Ronaldo N M; Cohen, Robert E; Rubner, Michael F

    2015-12-30

    Cell backpacks, or micron-scale patches of a few hundred nanometers in thickness fabricated by layer-by-layer (LbL) assembly, are potentially useful vehicles for targeted drug delivery on the cellular level. In this work, echogenic liposomes (ELIPs) containing the anticancer drug doxorubicin (DOX) are embedded into backpacks through electrostatic interactions and LbL assembly. Poly(allylamine hydrochloride)/poly(acrylic acid) (PAH/PAA)n , and poly(diallyldimethylammonium chloride)/poly(styrene sulfonate) (PDAC/SPS)n film systems show the greatest ELIP incorporation of the films studied while maintaining the structural integrity of the vesicles. The use of ELIPs for drug encapsulation into backpacks facilitates up to three times greater DOX loading compared to backpacks without ELIPs. Cytotoxicity studies reveal that monocyte backpack conjugates remain viable even after 72 h, demonstrating promise as drug delivery vehicles. Because artificial vesicles can load many different types of drugs, ELIP containing backpacks offer a unique versatility for broadening the range of possible applications for cell backpacks. PMID:26616471

  5. In vivo toxicity of cationic micelles and liposomes

    DEFF Research Database (Denmark)

    Knudsen, Kristina Bram; Northeved, Helle; Ek, Pramod Kumar;

    2015-01-01

    This study investigated toxicity of nanocarriers comprised of cationic polymer and lipid components often used in gene and drug delivery, formulated as cationic micelles and liposomes. Rats were injected intravenously with 10, 25 or 100 mg/kg and sacrificed after 24 or 48 h, or 24 h after the las...

  6. Temperature-controlled interaction of thermosensitive polymer-modified cationic liposomes with negatively charged phospholipid membranes.

    Science.gov (United States)

    Kono, K; Henmi, A; Takagishi, T

    1999-09-21

    To obtain cationic liposomes of which affinity to negatively charged membranes can be controlled by temperature, cationic liposomes consisting of 3beta-[N-(N', N'-dimethylaminoethane)carbamoyl]cholesterol and dioleoylphosphatidylethanolamine were modified with poly(N-acryloylpyrrolidine), which is a thermosensitive polymer exhibiting a lower critical solution temperature (LCST) at ca. 52 degrees C. The unmodified cationic liposomes did not change its zeta potential between 20-60 degrees C. The polymer-modified cationic liposomes revealed much lower zeta potential values below the LCST of the polymer than the unmodified cationic liposomes. However, their zeta potential increased significantly above this temperature. The unmodified cationic liposomes formed aggregates and fused intensively with anionic liposomes consisting of egg yolk phosphatidylcholine and phosphatidic acid in the region of 20-60 degrees C, due to the electrostatic interaction. In contrast, aggregation and fusion of the polymer-modified cationic liposomes with the anionic liposomes were strongly suppressed below the LCST. However, these interactions were enhanced remarkably above the LCST. In addition, the polymer-modified cationic liposomes did not cause leakage of calcein from the anionic liposomes below the LCST, but promoted the leakage above this temperature as the unmodified cationic liposomes did. Temperature-induced conformational change of the polymer chains from a hydrated coil to a dehydrated globule might affect the affinity of the polymer-modified cationic liposomes to the anionic liposomes. PMID:10561483

  7. Preparation of stealth cationic liposome loaded with doxorubicin and cell studies in vitro%新型阿霉素隐形阳离子脂质体的制备及体外细胞实验

    Institute of Scientific and Technical Information of China (English)

    吉丽; 常爽; 何斌; 李莉; 聂宇; 顾忠伟

    2012-01-01

    目的 制备阿霉素隐形阳离子脂质体( DOX - SCL),并与中性脂质体(DOX - SNL)比较在体外小鼠乳腺癌4T1细胞实验上的差异.方法 采用薄膜超声法制备空白脂质体,硫酸铵梯度法包载盐酸阿霉素(DOX);引入赖氨酸-胆固醇酯( Chol - lys)制成阳离子脂质体(CL),同时引入聚乙二醇-胆固醇琥珀酸酯(CHEMS-PEG)制成隐形阳离子脂质体(SCL);采用凝胶柱- UV法测定包封率;采用MTT法测定细胞毒性及体外抗肿瘤活性;通过流式细胞试验考察4T1细胞对脂质体的摄取情况.结果 SCL粒径约为100 nm,Zeta电位约为15.2 mV,对DOX的包封率大于95%;CHEMS - PEG的引入可以有效地降低CL的细胞毒性;与DOX-SNL相比,4T1细胞对DOX-SCL的摄取有所增加,DOX - SCL对4T1细胞的抑制率也更高.结论 SCL作为新型药物载体,可有效地促进DOX在肿瘤细胞中的传递.%OBJECTIVE To prepare the stealth cationic liposome (SCL) loaded with doxorubicin (DOX) ,and investigate the difference between DOX - SCL and neutral liposome (DOX - SNL) on murine breast carcinoma 4T1 cell line in vitro. METHODS lipo-somes loaded with DOX were prepared by film dispersion followed by ammonium sulfate gradient method. Cationic liposome ( CL) was formed in the addition of lysine - based cholesterol ( Chol- lys) , while SCL was constructed with both Chol- lys and PEGylated cholesterol hemisuccinate ( CHEMS - PEG). The entrapment efficiency was determined by Sephadex G -75 - UV. Cytotoxicity and anti -tumor activity in vitro were evaluated by MTT method. Flow cytometry was performed to evaluate the cellular uptake of liposomes by 4T1 cells. RESULTS The results revealed that the mean size of SCL was around 100 nm,with a Zeta potential of 15. 2 mV, and the entrapment efficiency was above 95%. The addition of CHEMS - PEG could effectively reduce the cytotoxicity of CL. Compared with DOX - SNL,the uptake of DOX - SCL by 4T1 cells was increased, and DOX - SCL showed

  8. In ovo transfection of chicken embryos using cationic liposomes.

    Science.gov (United States)

    Rosenblum, C I; Chen, H Y

    1995-05-01

    It is reported that cationic liposomes are capable of transfecting embryos in unincubated fertile chicken eggs and that the cationic liposome, TransfectAce, has superior properties to Lipofectin. In order to determine the duration of expression of genes introduced in this way, embryos were transfected with an expression vector encoding the firefly luciferase cDNA under the control of the Rous sarcoma virus long terminal repeat (LTR). Luciferase activity could be observed consistently in day 3 embryos and activity was detectable up to day 8 of incubation. The relative expression of luciferase under the control of different viral promoters was compared in transfected chicken embryo fibroblasts and day 3 embryos. The cytomegalovirus immediate early promoter and the SV40 early promoter directed the highest amount of expression in fibroblasts while the Rous sarcoma virus LTR caused the highest amount of expression in embryos. Chicken embryo fibroblasts were transfected with the luciferase vector in order to examine duration of reporter gene expression in vitro. Luciferase expression was decreased exponentially over a 24-day period after which point luciferase activity could no longer be detected. These data suggest that stable integration of transfected DNA using liposomes is a rare event. Nevertheless, liposome-mediated transfection of embryos is suitable for the examination of promoter activity in vivo and may be a useful method to transfect genes to study embryonic development. PMID:7795662

  9. Biophysical characterization of gold nanoparticles-loaded liposomes.

    Science.gov (United States)

    Mady, Mohsen Mahmoud; Fathy, Mohamed Mahmoud; Youssef, Tareq; Khalil, Wafaa Mohamed

    2012-10-01

    Gold nanoparticles were prepared and loaded into the bilayer of dipalmitoylphosphatidylcholine (DPPC) liposomes, named as gold-loaded liposomes. Biophysical characterization of gold-loaded liposomes was studied by transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectroscopy as well as turbidity and rheological measurements. FTIR measurements showed that gold nanoparticles made significant changes in the frequency of the CH(2) stretching bands, revealing that gold nanoparticles increased the number of gauche conformers and create a conformational change within the acyl chains of phospholipids. The transmission electron micrographs (TEM) revealed that gold nanoparticles were loaded in the liposomal bilayer. The zeta potential of DPPC liposomes had a more negative value after incorporating of Au NPs into liposomal membranes. Turbidity studies revealed that the loading of gold nanoparticles into DPPC liposomes results in shifting the temperature of the main phase transition to a lower value. The membrane fluidity of DPPC bilayer was increased by loading the gold nanoparticles as shown from rheological measurements. Knowledge gained in this study may open the door to pursuing liposomes as a viable strategy for Au NPs delivery in many diagnostic and therapeutic applications. PMID:22027546

  10. Delivery of siRNA Using Cationic Liposomes Incorporating Stearic Acid-modified Octa-Arginine.

    Science.gov (United States)

    Yang, Dongsheng; Li, Yuhuan; Qi, Yuhang; Chen, Yongzhen; Yang, Xuewei; Li, Yujing; Liu, Songcai; Lee, Robert J

    2016-07-01

    Cationic liposomes incorporating stearic acid-modified octa-arginine (StA-R8) were evaluated for survivin small interfering RNA (siRNA) delivery. StA-R8 was synthesized and incorporated into liposomes. The composition of liposomes was optimized. Physicochemical properties, cytotoxicity, cellular uptake and gene silencing activity of the liposomes complexed to survivin siRNA were investigated. The results showed that StA-R8-containing liposomes had reduced cytotoxicity and improved delivery efficiency of siRNA into cancer cells compared with StA-R8 by itself. PMID:27354583

  11. 64Cu loaded liposomes as positron emission tomography imaging agents

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa; Binderup, Tina; Rasmussen, Palle;

    2011-01-01

    -radionuclide (64Cu) using a new ionophore, 2-hydroxyquinoline, to carry 64Cu(II) across the membrane of preformed liposomes and deliver it to an encapsulated copper-chelator. Using this ionophore we achieved very efficient loading (95.5 ± 1.6%) and retention stability (>99%), which makes the 64Cu-liposomes highly...

  12. The preparation of Tc-99m labeled liposomes by a cationic SP/DOPE formulation for tumor imaging

    International Nuclear Information System (INIS)

    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

  13. Toxicity and immunomodulatory activity of liposomal vectors formulated with cationic lipids toward immune effector cells.

    Science.gov (United States)

    Filion, M C; Phillips, N C

    1997-10-23

    Liposomal vectors formulated with cationic lipids (cationic liposomes) and fusogenic dioleoylphosphatidylethanolamine (DOPE) have potential for modulating the immune system by delivering gene or antisense oligonucleotide inside immune cells. The toxicity and the immunoadjuvant activity of cationic liposomes containing nucleic acids toward immune effector cells has not been investigated in detail. In this report, we have evaluated the toxicity of liposomes formulated with various cationic lipids towards murine macrophages and T lymphocytes and the human monocyte-like U937 cell line. The effect of these cationic liposomes on the synthesis of two immunomodulators produced by activated macrophages, nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha), has also been determined. We have found that liposomes formulated from DOPE and cationic lipids based on diacyltrimethylammonium propane (dioleoyl-, dimyristoyl-, dipalmitoyl-, disteroyl-: DOTAP, DMTAP, DPTAP, DSTAP) or dimethyldioctadecylammonium bromide (DDAB) are highly toxic in vitro toward phagocytic cells (macrophages and U937 cells), but not towards non-phagocytic T lymphocytes. The rank order of toxicity was DOPE/DDAB > DOPE/DOTAP > DOPE/DMTAP > DOPE/DPTAP > DOPE/DSTAP. The ED50's for macrophage toxicity were 1000 nmol/ml for DOPE/DSTAP. The incorporation of DNA (antisense oligonucleotide or plasmid vector) into the cationic liposomes marginally reduced their toxicity towards macrophages. Although toxicity was observed with cationic lipids alone, it was clearly enhanced by the presence of DOPE. The replacement of DOPE by dipalmitoylphosphatidylcholine (DPPC) significantly reduced liposome toxicity towards macrophages, and the presence of dipalmitoylphosphatidylethanolamine-PEG2000 (DPPE-PEG2000: 10 mol%) in the liposomes completely abolished this toxicity. Cationic liposomes, irrespective of their DNA content, downregulated NO and TNF-alpha synthesis by lipopolysaccharide (LPS)/interferon-gamma (IFN

  14. Gene vectors based on DOEPC/DOPE mixed cationic liposomes : a physicochemical study

    NARCIS (Netherlands)

    Munoz-Ubeda, Monica; Rodriguez-Pulido, Alberto; Nogales, Aurora; Llorca, Oscar; Quesada-Perez, Manuel; Martin-Molina, Alberto; Aicart, Emilio; Junquera, Elena

    2011-01-01

    A double approach, experimental and theoretical, has been followed to characterize from a physicochemical standpoint the compaction process of DNA by means of cationic colloidal aggregates. The colloidal vectors are cationic liposomes constituted by a mixture of a novel cationic lipid, 1,2-dioleoyl-

  15. A novel cationic liposome formulation for efficient gene delivery via a pulmonary route

    Science.gov (United States)

    Li, Peng; Liu, Donghua; Sun, Xiaoli; Liu, Chunxi; Liu, Yongjun; Zhang, Na

    2011-06-01

    The clinical success of gene therapy for lung cancer is not only dependent on efficient gene carriers but also on a suitable delivery route. A pulmonary delivery route can directly deliver gene vectors to the lung which is more efficient than a systemic delivery route. For gene carriers, cationic liposomes have recently emerged as leading non-viral vectors in worldwide gene therapy clinical trials. However, cytotoxic effects or apoptosis are often observed which is mostly dependent on the cationic lipid used. Therefore, an efficient and safe cationic lipid, 6-lauroxyhexyl lysinate (LHLN), previously synthesized by our group was first used to prepare cationic liposomes. Physicochemical and biological properties of LHLN-liposomes were investigated. LHLN-liposome/DNA complexes showed positive surface charge, spherical morphology, a relatively narrow particle size distribution and strong DNA binding capability. Compared with Lipofectamine2000, the new cationic liposome formulation using LHLN exhibited not only lower cytotoxicity (P transfection efficiency in A549 and HepG2 lung cancer cells for in vitro tests. When administered by intratracheal instillation into rat lungs for in vivo evaluation, LHLN-liposome/DNA complexes exhibited higher pulmonary gene transfection efficiency than Lipofectamine2000/DNA complexes (P < 0.05). These results suggested that LHLN-liposomes may have great potential for efficient pulmonary gene delivery.

  16. A novel cationic liposome formulation for efficient gene delivery via a pulmonary route

    International Nuclear Information System (INIS)

    The clinical success of gene therapy for lung cancer is not only dependent on efficient gene carriers but also on a suitable delivery route. A pulmonary delivery route can directly deliver gene vectors to the lung which is more efficient than a systemic delivery route. For gene carriers, cationic liposomes have recently emerged as leading non-viral vectors in worldwide gene therapy clinical trials. However, cytotoxic effects or apoptosis are often observed which is mostly dependent on the cationic lipid used. Therefore, an efficient and safe cationic lipid, 6-lauroxyhexyl lysinate (LHLN), previously synthesized by our group was first used to prepare cationic liposomes. Physicochemical and biological properties of LHLN-liposomes were investigated. LHLN-liposome/DNA complexes showed positive surface charge, spherical morphology, a relatively narrow particle size distribution and strong DNA binding capability. Compared with Lipofectamine2000, the new cationic liposome formulation using LHLN exhibited not only lower cytotoxicity (P < 0.05) but also similar transfection efficiency in A549 and HepG2 lung cancer cells for in vitro tests. When administered by intratracheal instillation into rat lungs for in vivo evaluation, LHLN-liposome/DNA complexes exhibited higher pulmonary gene transfection efficiency than Lipofectamine2000/DNA complexes (P < 0.05). These results suggested that LHLN-liposomes may have great potential for efficient pulmonary gene delivery.

  17. Preparation of oligodeoxynucleotide encapsulated cationic liposomes and release study with models of cellular membranes

    OpenAIRE

    Tamaddon AM.; Hosseini-Shirazi F.; Moghimi HR

    2007-01-01

    Cationic liposomes are used for cellular delivery of antisense oligodeoxynucleotide (AsODN), where release of encapsulated AsODN is mainly controlled by endocytosis and fusion mechanisms. In this investigation, it was tried to model such a release process that is difficult to evaluate in cell culture. For this purpose, an AsODN model (against protein kinase C-α) was encapsulated in a DODAP-containing cationic liposome and evaluated for size, zeta-potential, encapsulation and ODN stab...

  18. Liposome drugs' loading efficiency: a working model based on loading conditions and drug's physicochemical properties.

    Science.gov (United States)

    Zucker, Daniel; Marcus, David; Barenholz, Yechezkel; Goldblum, Amiram

    2009-10-01

    Remote loading of liposomes by transmembrane gradients is one of the best approaches for achieving the high enough drug level per liposome required for the liposomal drug to be therapeutically efficacious. This breakthrough, which enabled the approval and clinical use of nanoliposomal drugs such as Doxil, has not been paralleled by an in-depth understanding that allows predicting loading efficiency of drugs. Here we describe how applying data-mining algorithms on a data bank based on Barenholz's laboratory's 15 years of liposome research experience on remote loading of 9 different drugs enabled us to build a model that relates drug physicochemical properties and loading conditions to loading efficiency. This model enables choosing candidate molecules for remote loading and optimizing loading conditions according to logical considerations. The model should also help in designing pro-drugs suitable for remote loading. Our approach is expected to improve and accelerate development of liposomal formulations for clinical applications. PMID:19508880

  19. Surface area of lipid membranes regulates the DNA-binding capacity of cationic liposomes

    Science.gov (United States)

    Marchini, Cristina; Montani, Maura; Amici, Augusto; Pozzi, Daniela; Caminiti, Ruggero; Caracciolo, Giulio

    2009-01-01

    We have applied electrophoresis on agarose gels to investigate the DNA-binding capacity of cationic liposomes made of cationic DC-cholesterol and neutral dioleoylphosphatidylethanolamine as a function of membrane charge density and cationic lipid/DNA charge ratio. While each cationic liposome formulation exhibits a distinctive DNA-protection ability, here we show that such a capacity is universally regulated by surface area of lipid membranes available for binding in an aspecific manner. The relevance of DNA protection for gene transfection is also discussed.

  20. 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. PMID:25704683

  1. Remote Loading of (64)Cu(2+) into Liposomes without the Use of Ion Transport Enhancers.

    Science.gov (United States)

    Henriksen, Jonas R; Petersen, Anncatrine L; Hansen, Anders E; Frankær, Christian G; Harris, Pernille; Elema, Dennis R; Kristensen, Annemarie T; Kjær, Andreas; Andresen, Thomas L

    2015-10-21

    Due to low ion permeability of lipid bilayers, it has been and still is common practice to use transporter molecules such as ionophores or lipophilic chelators to increase transmembrane diffusion rates and loading efficiencies of radionuclides into liposomes. Here, we report a novel and very simple method for loading the positron emitter (64)Cu(2+) into liposomes, which is important for in vivo positron emission tomography (PET) imaging. By this approach, copper is added to liposomes entrapping a chelator, which causes spontaneous diffusion of copper across the lipid bilayer where it is trapped. Using this method, we achieve highly efficient (64)Cu(2+) loading (>95%), high radionuclide retention (>95%), and favorable loading kinetics, excluding the use of transporter molecule additives. Therefore, clinically relevant activities of 200-400 MBq/patient can be loaded fast (60-75 min) and efficiently into preformed stealth liposomes avoiding subsequent purification steps. We investigate the molecular coordination of entrapped copper using X-ray absorption spectroscopy and demonstrate high adaptability of the loading method to pegylated, nonpegylated, gel- or fluid-like, cholesterol rich or cholesterol depleted, cationic, anionic, and zwitterionic lipid compositions. We demonstrate high in vivo stability of (64)Cu-liposomes in a large canine model observing a blood circulation half-life of 24 h and show a tumor accumulation of 6% ID/g in FaDu xenograft mice using PET imaging. With this work, it is demonstrated that copper ions are capable of crossing a lipid membrane unassisted. This method is highly valuable for characterizing the in vivo performance of liposome-based nanomedicine with great potential in diagnostic imaging applications. PMID:26426093

  2. Transdermal Delivery of Small Interfering RNA with Elastic Cationic Liposomes in Mice

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Hattori

    2013-01-01

    Full Text Available We developed elastic cationic liposomal vectors for transdermal siRNA delivery. These liposomes were prepared with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP as a cationic lipid and sodium cholate (NaChol or Tween 80 as an edge activator. When NaChol or Tween 80 was included at 5, 10, and 15% (w/w into DOTAP liposomal formulations (C5-, C10-, and C15-liposomes and T5-, T10-, and T15-liposomes, C15- and T10-liposomes showed 2.4- and 2.7-fold-higher elasticities than DOTAP liposome, respectively. Although the sizes of all elastic liposomes prepared in this study were about 80–90 nm, the sizes of C5-, C10- and C15-liposome/siRNA complexes (lipoplexes were about 1,700–1,800 nm, and those of T5-, T10-, and T15-lipoplexes were about 550–780 nm. Their elastic lipoplexes showed strong gene suppression by siRNA without cytotoxicity when transfected into human cervical carcinoma SiHa cells. Following skin application of the fluorescence-labeled lipoplexes in mice, among the elastic lipoplexes, C15- and T5-lipoplexes showed effective penetration of siRNA into skin, compared with DOTAP lipoplex and free siRNA solution. These data suggest that elastic cationic liposomes containing an appropriate amount of NaChol or Tween 80 as an edge activator could deliver siRNA transdermally.

  3. Potentiating effects of MPL on DSPC bearing cationic liposomes promote recombinant GP63 vaccine efficacy: high immunogenicity and protection.

    Directory of Open Access Journals (Sweden)

    Saumyabrata Mazumder

    2011-12-01

    Full Text Available 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

  4. Hepatocytes targeting of cationic liposomes modified with soybean sterylglucoside and polyethylene glycol

    Institute of Scientific and Technical Information of China (English)

    Xian-Rong Qi; Wen-Wei Yan; Jing Shi

    2005-01-01

    AIM: In this study, a hepatocyte-specific targeting technology was developed by modifying cationic liposomes with soybean sterylglucoside (SG) and polyethylene glycol (PEG) (C/SG/PEG-liposomes).METHODS: The liposomal transfection efficiencies in HepG22.2.15 cells were estimated with the use of fluorescein sodium (FS) as a model drug, by flow cytometry. The antisense activity of C/SG/PEG-liposomes entrapped antisense oligonucleotides (ODN) was determined as HBsAg and HBeAg in HepG2 2.2.15 cells by ELISA. The liposome uptake by liver and liver cells in mice was carried out after intravenous injection of 3H-labeled liposomes.RESULTS: C/SG-liposomes entrapped FS were effectively transfected into HepG2 2.2.15 cells in vitro. C/SG/PEGliposomes entrapped ODN, reduced the secretion of both HBsAg and HBeAg in HepG2 2.2.15 cells when compared to free ODN. After in vivo injection of 3H-labeled C/SG/PEG-liposomes, higher radiation accumulation was observed in the hepatocytes than non-parenchymal cells of the liver.CONCLUSION: C/SG/PEG-liposomes mediated gene transfer to the liver is an effective gene-delivery method for hepatocytes-specific targeting, which appears to have a potential for gene therapy of HBV infections.

  5. Drug loading to lipid-based cationic nanoparticles

    International Nuclear Information System (INIS)

    Lipid-based cationic nanoparticles are a new promising option for tumor therapy, because they display enhanced binding and uptake at the neo-angiogenic endothelial cells, which a tumor needs for its nutrition and growth. By loading suitable cytotoxic compounds to the cationic carrier, the tumor endothelial and consequently also the tumor itself can be destroyed. For the development of such novel anti-tumor agents, the control of drug loading and drug release from the carrier matrix is essential. We have studied the incorporation of the hydrophobic anti-cancer agent Paclitaxel (PXL) into a variety of lipid matrices by X-Ray reflectivity measurements. Liposome suspensions from cationic and zwitterionic lipids, comprising different molar fractions of Paclitaxel, were deposited on planar glass substrates. After drying at controlled humidity, well ordered, oriented multilayer stacks were obtained, as proven by the presence of bilayer Bragg peaks to several orders in the reflectivity curves. The presence of the drug induced a decrease of the lipid bilayer spacing, and with an excess of drug, also Bragg peaks of drug crystals could be observed. From the results, insight into the solubility of Paclitaxel in the model membranes was obtained and a structural model of the organization of the drug in the membrane was derived. Results from subsequent pressure/area-isotherm and grazing incidence diffraction (GID) measurements performed with drug/lipid Langmuir monolayers were in accordance with these conjectures

  6. Arginine-based cationic liposomes for efficient in vitro plasmid DNA delivery with low cytotoxicity

    Directory of Open Access Journals (Sweden)

    Sarker SR

    2013-04-01

    Full Text Available Satya Ranjan Sarker, Yumiko Aoshima, Ryosuke Hokama, Takafumi Inoue, Keitaro Sou, Shinji Takeoka Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University (TWIns, Tokyo, Japan Background: Currently available gene delivery vehicles have many limitations such as low gene delivery efficiency and high cytotoxicity. To overcome these drawbacks, we designed and synthesized two cationic lipids comprised of n-tetradecyl alcohol as the hydrophobic moiety, 3-hydrocarbon chain as the spacer, and different counterions (eg, hydrogen chloride [HCl] salt or trifluoroacetic acid [TFA] salt in the arginine head group. Methods: Cationic lipids were hydrated in 4-(2-hydroxyethyl-1-piperazineethanesulfonic acid (HEPES buffer to prepare cationic liposomes and characterized in terms of their size, zeta potential, phase transition temperature, and morphology. Lipoplexes were then prepared and characterized in terms of their size and zeta potential in the absence or presence of serum. The morphology of the lipoplexes was determined using transmission electron microscopy and atomic force microscopy. The gene delivery efficiency was evaluated in neuronal cells and HeLa cells and compared with that of lysine-based cationic assemblies and Lipofectamine™ 2000. The cytotoxicity level of the cationic lipids was investigated and compared with that of Lipofectamine™ 2000. Results: We synthesized arginine-based cationic lipids having different counterions (ie, HCl-salt or TFA-salt that formed cationic liposomes of around 100 nm in size. In the absence of serum, lipoplexes prepared from the arginine-based cationic liposomes and plasmid (p DNA formed large aggregates and attained a positive zeta potential. However, in the presence of serum, the lipoplexes were smaller in size and negative in zeta potential. The morphology of the lipoplexes was vesicular. Arginine-based cationic liposomes with HCl-salt showed the

  7. Dextran sulfate-dependent fusion of liposomes containing cationic stearylamine.

    Science.gov (United States)

    Zschörnig, O; Arnold, K; Richter, W; Ohki, S

    1992-11-01

    The incorporation of the positively charged stearylamine into phosphatidylcholine liposomes was studied by measuring electrophoretic mobilities. Up to a molar ratio SA/PC = 0.5 an increase of the positive zeta potential can be observed. Addition of the negatively charged macromolecule dextran sulfate leads to a change of the sign of the surface potential of the PC/SA liposomes indicating binding of the macromolecule to the surface. This process is accompanied by an increase in turbidity, which is dependent on the molecular weight of the dextran sulfate and the SA concentration (measured by turbidimetry). Using the NBD/Rh and Pyr-PC fluorescence assays the fusion of SA containing liposomes was investigated. A strong influence of the SA content and molecular weight of dextran sulfate on the fusion extent was observed. The fusion extent is proportional to the SA content in the PC membrane and the molecular weight of dextran sulfate. PC/SA/PE liposomes exhibit a higher fusion extent after addition of dextran sulfate compared to PC/SA liposomes indicating that PE additionally destabilizes the bilayer. Freeze-fracture electron microscopy reveals that the reaction products are large complexes composed of multilamellar stacks of tightly packed, straight membranes and aggregated vesicles. The tight packing of the membranes in the stacks (and the narrow contact of the aggregated vesicles) indicates a strong adherence of opposite membrane surfaces induced by dextran sulfate. PMID:1486657

  8. Role of the charge, carbon chain length, and content of surfactant on the skin penetration of meloxicam-loaded liposomes

    Directory of Open Access Journals (Sweden)

    Duangjit S

    2014-04-01

    Full Text Available Sureewan Duangjit,1,2 Boonnada Pamornpathomkul,1 Praneet Opanasopit,1 Theerasak Rojanarata,1 Yasuko Obata,2 Kozo Takayama,2 Tanasait Ngawhirunpat11Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand; 2Department of Pharmaceutics, Hoshi University, Shinagawa-ku, Tokyo, JapanAbstract: The objective of this study was to investigate the influence of surfactant charge, surfactant carbon chain length, and surfactant content on the physicochemical characteristics (ie, vesicle size, zeta potential, elasticity, and entrapment efficiency, morphology, stability, and in vitro skin permeability of meloxicam (MX-loaded liposome. Moreover, the mechanism for the liposome-enhanced skin permeation of MX was determined by Fourier transform infrared spectroscopy and differential scanning calorimetry. The model formulation used in this study was obtained using a response surface method incorporating multivariate spline interpolation (RSM-S. Liposome formulations with varying surfactant charge (anionic, neutral, and cationic, surfactant carbon chain length (C4, C12, and C16, and surfactant content (10%, 20%, and 29% were prepared. The formulation comprising 29% cationic surfactant with a C16 chain length was found to be the optimal liposome for the transdermal delivery of MX. The skin permeation flux of the optimal formulation was 2.69-fold higher than that of a conventional liposome formulation. Our study revealed that surfactants affected the physicochemical characteristics, stability, and skin permeability of MX-loaded liposomes. These findings provide important fundamental information for the development of liposomes as transdermal drug delivery systems.Keywords: optimal liposome, optimization, transdermal drug delivery, surfactant charge, surfactant carbon chain length, surfactant content

  9. Monocyte targeting and activation by cationic liposomes formulated with a TLR7 agonist

    DEFF Research Database (Denmark)

    Johansen, Pia Thermann; Zucker, Daniel; Parhamifar, Ladan;

    2015-01-01

    induction of IL-6 and IL-12p40, and differentiation into CD14+ and DC-SIGN+ DCs.Conclusion: Our present liposomes selectively target monocytes in fresh blood, enabling delivery of TLR7 agonists to the intracellular TLR7 receptor, with subsequent monocyte activation and boost in secretion of proinflammatory...... surface chemistry.Methods: Liposomes were extruded at 100 nm, incubated with fresh blood, followed by leukocyte analyses by FACS. Liposomes with and without the TLR7 agonist TMX-202 were incubated with fresh blood, and monocyte activation measured by cytokine secretion by ELISA and CD14 and DC......-SIGN expression.Results: The liposonnes target nnonocytes specifically over lymphocytes and granulocytes in human whole blood, and show association with 75 - 95% of the nnonocytes after 1 h incubation. Formulations of TMX-202 in cationic liposomes were potent in targeting and activation of monocytes, with strong...

  10. (99m)Tc-labeled therapeutic inhaled amikacin loaded liposomes.

    Science.gov (United States)

    Lee, Jae-Ho; Cheng, Kenneth T; Malinin, Vladimir; Li, Zhili; Yao, Zhengsheng; Lee, Sung-Jin; Gould, Christine M; Olivier, Kenneth N; Chen, Clara; Perkins, Walter R; Paik, Chang H

    2013-12-01

    The radiolabeling of the liposome surface can be a useful tool for in vivo tracking of therapeutic drug loaded liposomes. We investigated radiolabeling therapeutic drug (i.e. an antibiotic, amikacin) loaded liposomes with (99m)Tc, nebulization properties of (99m)Tc-labeled liposomal amikacin for inhalation ((99m)Tc-LAI), and its stability by size exclusion low-pressure liquid chromatography (LPLC). LAI was reacted with (99m)Tc using SnCl2 dissolved in ascorbic acid as a reducing agent for 10 min at room temperature. The labeled products were then purified by anion exchange resin. The purified (99m)Tc-LAI in 1.5% NaCl solution was incubated at 4 °C to assess its stability by LPLC. The purified (99m)Tc-LAI was subjected to studies with a clinically used nebulizer (PARI eFlow®) and the Anderson Cascade Impactor (ACI). The use of ascorbic acid at 0.91 mM resulted in a quantitative labeling efficiency. The LPLC profile showed that the liposomal peak of LAI detected by a UV monitor at both 200 nm and 254 nm overlapped with the radioactivity peak of (99m)Tc-LAI, indicating that (99m)Tc-LAI is suitable for tracing LAI. The ACI study demonstrated that the aerosol droplet size distribution determined gravimetrically was similar to that determined by radioactivity. The liposome surface labeling method using SnCl₂ in 0.91 mM ascorbic acid produced (99m)Tc-LAI with a high labeling efficiency and stability that are adequate to evaluate the deposition and clearance of inhaled LAI in the lung by gamma scintigraphy. PMID:23879241

  11. Enhancement of gene transduction efficiency in cancer cells using cationic liposome with hyperthermia.

    Directory of Open Access Journals (Sweden)

    Mushiake H

    2002-02-01

    Full Text Available We evaluated the effects of hyperthermia on the efficiency of gene transduction by using a cationic liposome to develop an efficient method for lipofection. We used Lewis lung carcinoma (LLC, NIH3T3, and A549 cell lines, with Lipofectamine reagent as the cationic liposome and the LacZ gene as the reporter gene. In LLC, co-incubation of the cationic liposome and plasmid DNA complex (lipoplex with the cells for 2 h at 41 degrees C enhanced the efficiency of gene transduction approximately 1.4-fold compared to incubation for 2 h at 37 degrees C, as measured by X-gal staining and beta-galactosidase activity. In cell lines NIH3T3 and A549, the efficiency of gene transduction showed a tendency toward enhancement after 2 h co-incubation with lipoplex at 41 degrees C compared to that at 37 degrees C, as measured by X-gal staining. This is the first study to demonstrate the enhancement of gene transduction efficiency achieved by using a cationic liposome under conditions of hyperthermia. This method should prove useful for lipofection in other cancer cells.

  12. Photodynamic therapy disinfection of carious tissue mediated by aluminum-chloride-phthalocyanine entrapped in cationic liposomes: an in vitro and clinical study.

    Science.gov (United States)

    Longo, João Paulo F; Leal, Soraya C; Simioni, Andreza R; de Fátima Menezes Almeida-Santos, Maria; Tedesco, Antônio C; Azevedo, Ricardo B

    2012-05-01

    Photodynamic therapy (PDT) is a technique employed in the treatment of several superficial infections, such as caries. PDT uses a non-toxic drug termed photosensitizer (PS) followed by light irradiation. The cytotoxic effects of the therapy are related to the production of reactive species produced after light activation of a photosensitizer, which reacts with surrounding molecules and disrupts several of the cell's functions. Within this context, this study aimed to develop a clinical protocol involving PDT application mediated by aluminum-chloride-phthalocyanine (AlClPc) entrapped in cationic liposomes against cariogenic bacteria in caries lesions. Cationic liposomes were used to delivery AlClPc preferentially to bacterial cells due to the strong anionic superficial charges of these cell types. The results are represented in two fundamental steps: (1) in vitro evaluation of AlClPc delivery to cariogenic bacteria and pulp cells, as well as its potential phototoxicity; (2) a clinical study involving volunteer patients that were treated with the PDT protocol mediated by AlClPc-cationic liposome. The main results showed that the AlClPc-cationic liposome was preferentially absorbed by bacterial cells compared to eukaryotic dental pulp cells, and it was efficient in the reduction of microbial load from bacterial cultures. In addition, the clinical study showed a mean reduction of 82% of total bacterial in the treated cavities after PDT application. Taken together, the results presented in this study showed that the antimicrobial PDT protocol mediated by cationic liposomes containing AlClPc is safety for clinical application and is efficient in the reduction of bacterial load in caries lesions. PMID:21809069

  13. Effect of Mechanical Agitation on Cationic Liposome Transport across an Unstirred Water Layer in Caco-2 Cells.

    Science.gov (United States)

    Kono, Yusuke; Iwasaki, Ayu; Matsuoka, Kenta; Fujita, Takuya

    2016-01-01

    To develop an effective oral delivery system for plasmid DNA (pDNA) using cationic liposomes, it is necessary to clarify the characteristics of uptake and transport of cationic liposome/pDNA complexes into the intestinal epithelium. In particular, evaluation of the involvement of an unstirred water layer (UWL), which is a considerable permeability barrier, in cationic liposome transport is very important. Here, we investigated the effects of a UWL on the transfection efficiency of cationic liposome/pDNA complexes into a Caco-2 cell monolayer. When Caco-2 cells were transfected with cationic liposome/pDNA complexes in shaking cultures to reduce the thickness of the UWL, gene expression was significantly higher in Caco-2 cells compared with static cultures. We also found that this enhancement of gene expression by shaking was not attributable to activation of transcription factors such as activator protein-1 and nuclear factor-kappaB (NF-κB). In addition, the increase in gene expression by mechanical agitation was observed at all charge ratios (1.5, 2.3, 3.1, 4.5) of cationic liposome/pDNA complexes. Transport experiments using Transwells demonstrated that mechanical agitation increased the uptake of cationic liposome/pDNA complexes by Caco-2 cells, whereas transport of the complexes across a Caco-2 cell monolayer did not occurr. Moreover, the augmentation of the gene expression of cationic liposome/pDNA complexes by shaking was observed in Madin-Darby canine kidney cells. These results indicate that a UWL greatly affects the uptake and transfection efficiency of cationic liposome/pDNA complexes into an epithelial monolayer in vitro. PMID:27476939

  14. DEVELOPMENT AND CHARACTARIZATION OF PERINDOPRIL ERBUMINE LOADED ETHANOLIC LIPOSOMES

    OpenAIRE

    Prakash Goudanavar; Manjunatha; Doddayya Hiremath

    2014-01-01

    The present work describes the preparation of Perindopril erbumine ethosomes and study of effect of alcohol and phospholipid on transdermal delivery. Perindopril erbumine is an ACE inhibitor which slowly inhibits the activity of the enzyme ACE, which decreases the production of angiotensin II, is being involved in the blood pressure regulation. Perindopril erbumine loaded ethanolic Liposomes were prepared by an hot - cold method using different concentrations of Alcohol and Soya lecithin in d...

  15. The effects of salt on the physicochemical properties and immunogenicity of protein based vaccine formulated in cationic liposome.

    Science.gov (United States)

    Yan, Weili; Huang, Leaf

    2009-02-23

    Recently, we have developed a simple and potent therapeutic cancer vaccine consisting of a cationic lipid and a peptide antigen. In this report, we expanded the utility of this formulation to protein based vaccines. First, we formulated the human papillomavirus (HPV) 16 E7 protein (E7) in different doses of DOTAP liposome. The results showed that these formulations failed to regress an established tumor. However, when sodium chloride (30 mM) was added to the DOTAP (100 nmol)/E7 (20 microg) formulation, anti-tumor activity was generated in the immunized mice. Correlatively, 30 mM NaCl in the DOTAP/E7 protein formulation increased the particle size from approximately 350 to 550 nm, decreased the protein loading capacity (from 95 to 90%), and finally increased the zeta potential (from 29 to 38 mV). Next, a model protein antigen ovalbumin (OVA) was formulated in different doses of DOTAP liposomes. Similarly, the results showed that 20 microg OVA formulated in 200 nmol DOTAP with 30 mM NaCl had the best OVA-specific antibody response, including both IgG(1) and IgG(2a), suggesting both Th1 and Th2 immune responses were generated by this formulation. In conclusion, we have expanded the application of cationic DOTAP liposome formulation to protein based vaccines and also identified that small amounts of salt could change the physicochemical properties of the vaccine formulation and enhance the activity of the DOTAP/protein based vaccine. The enhancement of immune responses by salt is possibly due to its interference of the electrostatic interaction between the cationic lipid and the protein antigen to facilitate the antigen release from the carrier and at the same time activate the antigen presenting cells. PMID:18992312

  16. Synthesis and validation of novel cholesterol-based fluorescent lipids designed to observe the cellular trafficking of cationic liposomes.

    Science.gov (United States)

    Kim, Bieong-Kil; Seu, Young-Bae; Choi, Jong-Soo; Park, Jong-Won; Doh, Kyung-Oh

    2015-09-15

    Cholesterol-based fluorescent lipids with ether linker were synthesized using NBD (Chol-E-NBD) or Rhodamine B (Chol-E-Rh), and the usefulnesses as fluorescent probes for tracing cholesterol-based liposomes were validated. The fluorescent intensities of liposomes containing these modified lipids were measured and observed under a microscope. Neither compound interfered with the expression of GFP plasmid, and live cell images were obtained without interferences. Changes in the fluorescent intensity of liposomes containing Chol-E-NBD were followed by flow cytometry for up to 24h. These fluorescent lipids could be useful probes for trafficking of cationic liposome-mediated gene delivery. PMID:26243368

  17. Carborane derivatives loaded into liposomes as efficient delivery systems for boron neutron capture therapy.

    Science.gov (United States)

    Altieri, S; Balzi, M; Bortolussi, S; Bruschi, P; Ciani, L; Clerici, A M; Faraoni, P; Ferrari, C; Gadan, M A; Panza, L; Pietrangeli, D; Ricciardi, G; Ristori, S

    2009-12-10

    Boron neutron capture therapy (BNCT) is an anticancer therapy based on the incorporation of (10)B in tumors, followed by neutron irradiation. Recently, the synthesis and delivery of new boronated compounds have been recognized as some of the main challenges in BNCT application. Here, we report on the use of liposomes as carriers for BNCT active compounds. Two carborane derivatives, i.e., o-closocarboranyl beta-lactoside (LCOB) and 1-methyl-o-closocarboranyl-2-hexylthioporphyrazine (H(2)PzCOB), were loaded into liposomes bearing different surface charges. The efficacy of these formulations was tested on model cell cultures, that is, DHD/K12/TRb rat colon carcinoma and B16-F10 murine melanoma. These induce liver and lung metastases, respectively, and are used to study the uptake of standard BNCT drugs, including borophenylalanine (BPA). Boron concentration in treated cells was measured by alpha spectrometry at the TRIGA mark II reactor (University of Pavia). Results showed high performance of the proposed formulations. In particular, the use of cationic liposomes increased the cellular concentration of (10)B by at least 30 times more than that achieved by BPA. PMID:19954249

  18. Preparation of oligodeoxynucleotide encapsulated cationic liposomes and release study with models of cellular membranes

    Directory of Open Access Journals (Sweden)

    Tamaddon AM.

    2007-05-01

    Full Text Available Cationic liposomes are used for cellular delivery of antisense oligodeoxynucleotide (AsODN, where release of encapsulated AsODN is mainly controlled by endocytosis and fusion mechanisms. In this investigation, it was tried to model such a release process that is difficult to evaluate in cell culture. For this purpose, an AsODN model (against protein kinase C-α was encapsulated in a DODAP-containing cationic liposome and evaluated for size, zeta-potential, encapsulation and ODN stability. Vesicular models of outer layer and total plasma membranes and early and late endosomal membranes were developed, based on lipid content and pH, using ether injection method. ODN release was determined by the fluorescence dequenching of encapsulated FITC-ODN. Zeta potential, size and ODN encapsulation efficiency of the prepared liposomes were -2.49 ± 7.15 mV, 108.4 nm and 73% respectively. ODN protection was 3-4 times more than that of conventional liposome/ODN complexation method. There was a correlation between model concentration and percent of ODN release. At 7.5 µM, the percent of released ODN was 76% for the cholesterol-free model of the late endosome and 16% for the early endosomal membrane; while the release was less than 11% for the models of plasma membrane. ODN release increased with temperature in the range of 4-37◦C for the late endosomal model, but not for others, possibly due to their high cholesterol contents or acidic pH. The interaction was fast and completed within 5 minutes and didn’t change in the range of 5-60 minutes. Our data are in agreement with published cell culture studies and reveal that cell-liposomes interaction can be modeled by lamellar membranes.

  19. Novel siRNA-loaded Bubble Liposomes with Ultrasound Exposure for RNA Interference

    Science.gov (United States)

    Endo-Takahashi, Yoko; Negishi, Yoichi; Suzuki, Ryo; Maruyama, Kazuo; Aramaki, Yukihiko

    2011-09-01

    Recently, we have developed novel polyethyleneglycol (PEG) modified liposomes (Bubble liposomes; BLs) entrapping an ultrasound (US) imaging gas, which can work as a gene delivery tool with US exposure. We have shown that the combination of BLs and US was also useful for the delivery of siRNA. However, for use in intravenous administration, there is room for improvement in the colocalization of BLs and siRNA in blood vessels and the stability of siRNA. In this study, we have attempted to prepare novel siRNA-loaded BLs (si-BLs) using cationic lipid, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). As a result, siRNA loaded onto the surface of BLs could be observed. Furthermore, siRNA-loaded BLs were stable even in the presence of serum. The specific gene silencing effect caused by transfection with si-BLs and US could be also observed. Thus, si-BLs with US-exposure may be a useful novel transfection method for siRNA delivery to a target tissue or organ via systemic injection.

  20. Europium chelate-loaded liposomes: a tool for the study of binding and integrity of liposomes.

    Science.gov (United States)

    Orellana, A; Laukkanen, M L; Keinänen, K

    1996-10-01

    Using the biotin-streptavidin interaction as a model, we investigated the suitability of lanthanide chelates as encapsulated liposomal labels in liposome-based binding assays. Large unilamellar phospholipid:cholesterol liposomes containing europium-DTPA chelate and biotinylated phosphatidylethanolamine were prepared by detergent dialysis. The resulting Eu-liposomes ([symbol: see text] 120 nm) bound specifically to streptavidin in microtiter wells as measured by time-resolved fluorometric assay (TRF). The intensity of fluorescence released from the bound liposomes was dependent on the concentration of biotin in the liposome membrane, the concentration of europium entrapped in the liposomes, the incubation time and the amount of liposomes used in the assay. The sensitivity of the TRF assay allowed the detection of binding of attomole quantities of liposomes. The streptavidin-immobilised liposomes subjected to porcine pancreatic phospholipase A2 (EC 3.1.1.4) and detergents displayed a dose-dependent release of the encapsulated europium. Lanthanide-chelate-liposomes should prove useful for studies addressing binding and stability of liposomes. PMID:8865811

  1. Melatonin loaded ethanolic liposomes: physicochemical characterization and enhanced transdermal delivery.

    Science.gov (United States)

    Dubey, Vaibhav; Mishra, Dinesh; Jain, N K

    2007-09-01

    The current investigation aims to evaluate the transdermal potential of novel ethanolic liposomes (ethosomes) bearing Melatonin (MT), an anti-jet lag agent associated with poor skin permeation and long lag time. MT loaded ethosomes were prepared and characterized for vesicular shape and surface morphology, vesicular size, entrapment efficiency, stability, in vitro skin permeation and in vivo skin tolerability. Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), and Dynamic Light Scattering (DLS) defined ethosomes as spherical, unilamellar structures having low polydispersity (0.032+/-0.011) and nanometric size range (122+/-3.5 nm). % Entrapment efficiency of MT in ethosomal carrier was found to be 70.71+/-1.4. Stability profile of prepared system assessed for 120 days revealed very low aggregation and growth in vesicular size (7.6+/-1.2%). MT loaded ethosomal carriers also provided an enhanced transdermal flux of 59.2+/-1.22 microg/cm2/h and decreased lag time of 0.9 h across human cadaver skin. Fourier Transform-Infrared (FT-IR) data generated to assess the fluidity of skin lipids after application of formulation revealed a greater mobility of skin lipids on application of ethosomes as compared to that of ethanol or plain liposomes. Skin permeation profile of the developed formulation further assessed by confocal laser scanning microscopy (CLSM) revealed an enhanced permeation of Rhodamine Red (RR) loaded formulations to the deeper layers of the skin (240 microm). Further, a better skin tolerability of ethosomal suspension on rabbit skin suggested that ethosomes may offer a suitable approach for transdermal delivery of melatonin. PMID:17452098

  2. Factorial design studies of antiretroviral drug-loaded stealth liposomal injectable: PEGylation, lyophilization and pharmacokinetic studies

    Science.gov (United States)

    Sudhakar, Beeravelli; Krishna, Mylangam Chaitanya; Murthy, Kolapalli Venkata Ramana

    2016-01-01

    The aim of the present study was to formulate and evaluate the ritonavir-loaded stealth liposomes by using 32 factorial design and intended to delivered by parenteral delivery. Liposomes were prepared by ethanol injection method using 32 factorial designs and characterized for various physicochemical parameters such as drug content, size, zeta potential, entrapment efficiency and in vitro drug release. The optimization process was carried out using desirability and overlay plots. The selected formulation was subjected to PEGylation using 10 % PEG-10000 solution. Stealth liposomes were characterized for the above-mentioned parameters along with surface morphology, Fourier transform infrared spectrophotometer, differential scanning calorimeter, stability and in vivo pharmacokinetic studies in rats. Stealth liposomes showed better result compared to conventional liposomes due to effect of PEG-10000. The in vivo studies revealed that stealth liposomes showed better residence time compared to conventional liposomes and pure drug solution. The conventional liposomes and pure drug showed dose-dependent pharmacokinetics, whereas stealth liposomes showed long circulation half-life compared to conventional liposomes and pure ritonavir solution. The results of statistical analysis showed significance difference as the p value is (<0.05) by one-way ANOVA. The result of the present study revealed that stealth liposomes are promising tool in antiretroviral therapy.

  3. Anti-Cancer Efficacy of Paclitaxel Loaded in pH Triggered Liposomes.

    Science.gov (United States)

    Jiang, Lei; He, Bin; Pan, Dayi; Luo, Kui; Yi, Qiangying; Gu, Zhongwei

    2016-01-01

    Smart liposomes that are responsive to the microenvironment of tumor tissue have been utilized to enhance chemotherapeutic efficiency. Here, we reported a novel liposome called Trojan horse liposome, which has a pH response, to enhance drug accumulation in tumor sites and intercellular uptake. L-lysine was used as a linker to connect 2,3-dimethylmaleic anhydride (DMA) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) to yield a DSPE-Lys-DMA (DLD) lipid. The pH-responsive DLD was mixed with other commercially available lipids to form liposomes. The size, morphology and zeta potential of the DLD liposomes (DLD-Lip) were measured. Paclitaxel (PTX) was loaded in the liposomes. The release profile, cellular uptake, in vitro and in vivo anticancer activity of the PTX-loaded liposomes were investigated. The results showed that the mean diameter of the liposomes was less than 200 nm. The zeta potential of the liposomes was negative at pH 7.4. However, it was transferred to positive at weak acidic pH values with the cleavage of DMA amide. The charge reversion of DMA in acidic environments facilitated the cellular internalization and endosome escape of DLD-Lip, which inhibited the proliferation of 4T1 cancer cells in vitro. The pH-responsive "Trojan horse"-like liposomes also exhibited efficient anticancer activity in the xenograft breast cancer model in vivo. PMID:27301174

  4. Effect of Cholesterol on the Properties of Spray-Dried Lysozyme-Loaded Liposomal Powders

    OpenAIRE

    Charnvanich, Dusadee; Vardhanabhuti, Nontima; Kulvanich, Poj

    2010-01-01

    The influence of cholesterol (Chol) in the liposomal bilayer on the properties of inhalable protein-loaded liposomal powders prepared by spray-drying technique was investigated. Lysozyme (LSZ) was used as a model protein. Feed solution for spray drying was prepared by direct mixing of aqueous solution of LSZ with mannitol solution and empty liposome dispersions composed of hydrogenated phosphatidylcholine and Chol at various molar ratios. The spray-dried powders were characterized with respec...

  5. Microfluidic Remote Loading for Rapid Single-Step Liposomal Drug Preparation

    OpenAIRE

    Hood, R. R.; Vreeland, W. N.; DeVoe, D. L.

    2014-01-01

    Microfluidic-directed formation of liposomes is combined with in-line sample purification and remote drug loading for single step, continuous-flow synthesis of nanoscale vesicles containing high concentrations of stably loaded drug compounds. Using an on-chip microdialysis element, the system enables rapid formation of large transmembrane pH and ion gradients, followed by immediate introduction of amphipathic drug for real-time remote loading into the liposomes. The microfluidic process enabl...

  6. Formulation and Characterization of Tamoxifen Loaded Stealth Liposomes for Breast Cance

    Directory of Open Access Journals (Sweden)

    Mali Deepak

    2013-03-01

    Full Text Available The present study deals with the formulation and in-vitro characterization of tamoxifen loaded stealth liposomes. Passive targeting by stealth liposomes, once combined with efficient intracellular delivery, may be a very useful strategy to improve the antitumor efficacy for the anticancer agents. Stealth liposomes were prepared by using Cholesterol, DMPC, DSPC, and Polyethylene Glycol 4000 (PEG 4000 in order to achieve prolonged circulation time and sustained release. The prepared liposomes were evaluated for size, shape, profile, degree of drug entrapment, and in-vitro release efficiency. The effect of various formulation and drug release was investigated.

  7. Sorafenib and gadolinium co-loaded liposomes for drug delivery and MRI-guided HCC treatment.

    Science.gov (United States)

    Xiao, Yanan; Liu, Yongjun; Yang, Shaomei; Zhang, Bo; Wang, Tianqi; Jiang, Dandan; Zhang, Jing; Yu, Dexin; Zhang, Na

    2016-05-01

    To improve the poor water solubility of sorafenib and to monitor its distribution and the early feedback effects on its in vivo treatment efficacy in a precise manner, sorafenib (SF) and gadolinium (Gd) co-loaded liposomes (SF/Gd-liposomes) were prepared. The simultaneous imaging and therapy efficacies of the SF/Gd-liposomes were tested. The solubility of SF in SF/Gd-liposomes was significantly increased from 0.21μg/mL to 250μg/mL. The imaging capability of SF/Gd-liposomes were tested by in-vitro and the in-vivo imaging ability tests and the results confirmed that SF/Gd-liposomes could be served as an effective contrast agent. The design of SF/Gd-liposomes allowed the MRI-guided in vivo visualization of the delivery and biodistribution of liposome. In the in vivo antitumor studies, SF/Gd-liposomes had better antitumor effects in H22 tumor-bearing mice than SF solution (oral or i.v. administration) (P<0.05). These findings indicated that the SF/Gd-liposomes could be used as the promising nano-carriers for the MRI-guided in vivo visualization of the delivery and HCC treatment. PMID:26844644

  8. Cationic liposomes formulated with DMPC and a gemini surfactant traverse the cell membrane without causing a significant bio-damage.

    Science.gov (United States)

    Stefanutti, E; Papacci, F; Sennato, S; Bombelli, C; Viola, I; Bonincontro, A; Bordi, F; Mancini, G; Gigli, G; Risuleo, G

    2014-10-01

    Cationic liposomes have been intensively studied both in basic and applied research because of their promising potential as non-viral molecular vehicles. This work was aimed to gain more information on the interactions between the plasmamembrane and liposomes formed by a natural phospholipid and a cationic surfactant of the gemini family. The present work was conducted with the synergistic use of diverse experimental approaches: electro-rotation measurements, atomic force microscopy, ζ-potential measurements, laser scanning confocal microscopy and biomolecular/cellular techniques. Electro-rotation measurements pointed out that the interaction of cationic liposomes with the cell membrane alters significantly its dielectric and geometric parameters. This alteration, being accompanied by significant changes of the membrane surface roughness as measured by atomic force microscopy, suggests that the interaction with the liposomes causes locally substantial modifications to the structure and morphology of the cell membrane. However, the results of electrophoretic mobility (ζ-potential) experiments show that upon the interaction the electric charge exposed on the cell surface does not vary significantly, pointing out that the simple adhesion on the cell surface of the cationic liposomes or their fusion with the membrane is to be ruled out. As a matter of fact, confocal microscopy images directly demonstrated the penetration of the liposomes inside the cell and their diffusion within the cytoplasm. Electro-rotation experiments performed in the presence of endocytosis inhibitors suggest that the internalization is mediated by, at least, one specific pathway. Noteworthy, the liposome uptake by the cell does not cause a significant biological damage. PMID:25017801

  9. One Step Encapsulation of Small Molecule Drugs in Liposomes via Electrospray-Remote Loading.

    Science.gov (United States)

    Duong, Anthony D; Collier, Michael A; Bachelder, Eric M; Wyslouzil, Barbra E; Ainslie, Kristy M

    2016-01-01

    Resiquimod is a Toll-like receptor (TLR) 7/8 agonist that has previously been used as a vaccine adjuvant, as a topical treatment of viral lesions and skin cancer, and as an antiviral treatment. We report on the combined application of remote loading and electrospray to produce liposomal resiquimod, with the broader goals of improving drug encapsulation efficiency and scalability of liposome production methods. Drug loading in liposomes increased from less than 1% to greater that 3% by mass when remote loading was used, whether the liposomes were generated by thin-film hydration or electrospray methods. Dynamic light scattering (DLS) determined mean vesicle diameters of 137 ± 11 nm and 103 ± 4 for the thin-film and electrospray methods, respectively. Transmission electron microscopy (TEM) images showed spherical vesicles with sizes consistent with the DLS measurements. In vitro drug release profiles found that most of the drug remained within the liposomes at both pH 5.5 and 7.4. The in vitro bioactivity of the liposomal drug was also demonstrated by the increase in nitrite production when RAW macrophages were exposed to the drug. Our findings indicate that the remotely loaded liposomes formed via the scalable electrospray method have characteristics comparable to those produced via conventional batch methods. The methods discussed here are not limited to the enhanced delivery of resiquimod. Rather, they should be readily adaptable to other compounds compatible with remote loading. PMID:26568143

  10. Reduced cytotoxicity and enhanced bioactivity of cationic antimicrobial peptides liposomes in cell cultures and 3D epidermis model against HSV.

    Science.gov (United States)

    Ron-Doitch, Sapir; Sawodny, Beate; Kühbacher, Andreas; David, Mirjam M Nordling; Samanta, Ayan; Phopase, Jaywant; Burger-Kentischer, Anke; Griffith, May; Golomb, Gershon; Rupp, Steffen

    2016-05-10

    Cationic antimicrobial peptides (AMPs) are part of the innate immunity, and act against a wide variety of pathogenic microorganisms by perturbation of the microorganism's plasma membrane. Although attractive for clinical applications, these agents suffer from limited stability and activity in vivo, as well as non-specific interaction with host biological membranes, leading to cytotoxic adverse effects. We hypothesized that encapsulation of AMPs within liposomes could result in reduced cytotoxicity, and with enhanced stability as well as bioactivity against herpes simplex virus 1 (HSV-1). We formulated nano-sized liposomal formulations of LL-37 and indolicidin, and their physicochemical properties, cellular uptake, in vitro cytotoxicity and antiviral efficacy have been determined. Lower cytotoxicity of LL-37 liposomes was found in comparison to indolicidin liposomes attributed to the superior physicochemical properties, and to the different degree of interaction with the liposomal membrane. The disc-like shaped LL-37 liposomes (106.8±10.1nm, shelf-life stability of >1year) were taken up more rapidly and to a significantly higher extent than the free peptide by human keratinocyte cell line (HaCaT), remained intact within the cells, followed by release of the active peptide within the cytoplasm and migration of the vesicles' lipids to the plasma membrane. LL-37 liposomes were found significantly less toxic than both the free agent and liposomal indolicidin. In the new 3D epidermis model (immortalized primary keratinocytes) liposomal LL-37 treatment (>20μM), but not free LL-37, efficiently protected the epidermis, inhibiting HSV-1 infection. This positive antiviral effect was obtained with no cytotoxicity even at very high concentrations (400μM). Thus, the antiviral activity of encapsulated LL-37 was significantly improved, expanding its therapeutic window. Liposomal LL-37 appears to be a promising delivery system for HSV therapy. PMID:27012977

  11. Cationic liposomes modified with non-ionic surfactants as effective non-viral carrier for gene transfer.

    Science.gov (United States)

    Huang, Yong-Zhuo; Gao, Jian-Qing; Chen, Jin-Liang; Liang, Wen-Quan

    2006-05-01

    A defined change in formulation components affects the physical and chemical characteristics of cationic liposomes (CLs) carriers in many ways. Therefore, a great degree of control can be exercised over the structure by modifying the CLs with various materials, leading to new innovations for carrier improvement. In the present study, surface modifications of cationic liposomes with non-ionic surfactants--sorbitan monoesters serials (Span 85, 80, 40 and 20) were carried out for developing a new gene transfer carrier. Span modified cationic liposomes (Sp-CLs) were prepared by reverse phase evaporation method (RPV) and self-assemble complexes of antisense oligonucleotides/surfactant modifying cationic liposomes were prepared by auto-coacervation through electrostatic effect. Characterization of Sp-CLs and the self-assembled complex was performed by electron microscope, particle size, zeta potential, turbidity and agarose electrophoresis. Furthermore, in vitro cellular uptake experiment showed that Span plays a role in enhancing the cellular uptake of encapsulated oligonucleotides mediated by Sp-CLs by the endocytosis-dependent route. CLs modified with Span 40 significantly facilitated the cellular uptake by COS-7 cells and HeLa cells; also showed some positive effect on gene expression. That suggests it is a potential non-viral carrier for efficient gene transfer. PMID:16626948

  12. α, ω-Cholesterol-Functionalized Low Molecular Weight Polyethylene Glycol as a Novel Modifier of Cationic Liposomes for Gene Delivery

    Directory of Open Access Journals (Sweden)

    Cui-Cui Ma

    2014-11-01

    Full Text Available Here, three novel cholesterol (Ch/low molecular weight polyethylene glycol (PEG conjugates, termed α, ω-cholesterol-functionalized PEG (Ch2-PEGn, were successfully synthesized using three kinds of PEG with different average molecular weight (PEG600, PEG1000 and PEG2000. The purpose of the study was to investigate the potential application of novel cationic liposomes (Ch2-PEGn-CLs containing Ch2-PEGn in gene delivery. The introduction of Ch2-PEGn affected both the particle size and zeta potential of cationic liposomes. Ch2-PEG2000 effectively compressed liposomal particles and Ch2-PEG2000-CLs were of the smallest size. Ch2-PEG1000 and Ch2-PEG2000 significantly decreased zeta potentials of Ch2-PEGn-CLs, while Ch2-PEG600 did not alter the zeta potential due to the short PEG chain. Moreover, the in vitro gene transfection efficiencies mediated by different Ch2-PEGn-CLs also differed, in which Ch2-PEG600-CLs achieved the strongest GFP expression than Ch2-PEG1000-CLs and Ch2-PEG2000-CLs in SKOV-3 cells. The gene delivery efficacy of Ch2-PEGn-CLs was further examined by addition of a targeting moiety (folate ligand in both folate-receptor (FR overexpressing SKOV-3 cells and A549 cells with low expression of FR. For Ch2-PEG1000-CLs and Ch2-PEG2000-CLs, higher molar ratios of folate ligand resulted in enhanced transfection efficacies, but Ch2-PEG600-CLs had no similar in contrast. Additionally, MTT assay proved the reduced cytotoxicities of cationic liposomes after modification by Ch2-PEGn. These findings provide important insights into the effects of Ch2-PEGn on cationic liposomes for delivering genes, which would be beneficial for the development of Ch2-PEGn-CLs-based gene delivery system.

  13. Enhanced Ehrlich tumor inhibition using DOX-NP™ and gold nanoparticles loaded liposomes

    Science.gov (United States)

    Mady, M. M.; Al-Shaikh, F. H.; Al-Farhan, F. F.; Aly, A. A.; Al-Mohanna, M. A.; Ghannam, M. M.

    2016-04-01

    Treatment with doxorubicin (DOX) is a common regime in treating various types of cancer. DOX-NP™ is one of a well established marketed liposomal formulation for DOX. It offers distinct advantages over conventional DOX in reducing the cardiac toxicity and increasing the tolerability and efficacy. Gold nanoparticles (GNPs), a typical biocompatible nanomaterial, have been widely used in biomedical engineering and bioanalytical applications such as biomedical imaging and biosensors. Ehrlich tumors were grown in female balb mice by subcutaneous injection of Ehrlich ascites carcinoma cells. Mice bearing Ehrlich tumor were injected with saline, free doxorubicin (DOX) in solution, gold nanoparticles loaded liposomes and commercial liposomal encapsulated doxorubicin (DOX-NP™). The results showed that GNPs loaded liposomes could enhance the antitumor activity of commercial liposomal formulation (DOX-NP™) and displayed significantly decreased systemic toxicity compared with free DOX and commercial liposomal formulation (DOX-NP™) at the equivalent dose. So the combination of GNPs and liposomes is expected to significantly increase the likelihood of cell killing and make it a promising new approach to cancer therapy.

  14. Glycyl-L-Histidyl-L-Liysine-Cu(2+) loaded liposome formulations

    OpenAIRE

    Setenay Erdem; Murat Türkoğlu

    2010-01-01

    Enhancement of collagen synthesis by glycyl-l-histidyl-l-lysine-Cu2+ (GHK-Cu) derivatives is well known. The different activities of GHK-Cu would be of interest for cosmetic applications. Liposomes provide many benefits as topical drug delivery systems. Structure of double layer and lipid composition of liposomes keep the active substance longer in skin and provide regularly release to the deeper skin layers. Our aim in this study was to prepare GHK-Cu loaded liposomes and characterize them t...

  15. DEVELOPMENT AND CHARACTARIZATION OF PERINDOPRIL ERBUMINE LOADED ETHANOLIC LIPOSOMES

    Directory of Open Access Journals (Sweden)

    Prakash Goudanavar

    2014-03-01

    Full Text Available The present work describes the preparation of Perindopril erbumine ethosomes and study of effect of alcohol and phospholipid on transdermal delivery. Perindopril erbumine is an ACE inhibitor which slowly inhibits the activity of the enzyme ACE, which decreases the production of angiotensin II, is being involved in the blood pressure regulation. Perindopril erbumine loaded ethanolic Liposomes were prepared by an hot - cold method using different concentrations of Alcohol and Soya lecithin in different ratios and propylene glycol. The prepared ethosomal formulations were subjected to Vesicle size analysis, Morphological studies, Entrapment efficiency, In vitro release, Stability studies, In vitro permeation study and kinetic data analysis. The vesicle size of ethosomes varied between 1.96±0.003 to 4.56±0.008 µm (Without sonication and from 1.62±1.31 to 1.99±1.02 µm (With sonication, Entrapment efficiency between 43.91±0.57 to 78.04±0.30%. FT-IR, DSC and Zetapotential studies revealed the integrity of the drug in the formulations. In vitro release profiles indicated that the highest % of drug release is 95.22±0.35 over period of 24 hrs with 30% alcohol & 2% phospholipid (ETH8 compared to other formulations. The in vitro permeation across rat abdominal skin for the optimized formulations ETH3 and ETH8 after 24 hrs was found to be 79.63% and 85.33% respectively. Stability studies indicated that, the prepared ethosomes remained stable at refrigeration (4-8˚C and room (25±2˚C temperature. The prepared ethosomes showed promising results under in vitro conditions.

  16. 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

  17. Effective transcutaneous immunization by antigen-loaded flexible liposome in vivo

    Directory of Open Access Journals (Sweden)

    Li N

    2011-12-01

    Full Text Available Ni Li1, Li-Hua Peng1, Xi Chen1, Shinsaku Nakagawa2, Jian-Qing Gao11Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China; 2Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, JapanBackground: Transcutaneous vaccines have received wide attention due to their easy-to-use, needle-free, noninvasive delivery. However, the novel barrier function of stratum corneum hinders the transport of antigen and adjuvant in transcutaneous immunization. Novel nanoscale delivery systems employing, for example, liposomes and nanoparticles, have been widely investigated to overcome the penetration barrier of stratum corneum for effective transcutaneous immunization.Objective: The objective of this study was to prepare two types of flexible liposomes and determine their efficacies for the transcutaneous delivery of antigen and the subsequent immune response induced in vivo.Methods: Ovalbumin (OVA liposome-based transcutaneous vaccines were prepared using reverse-phase evaporation and film-dispersion methods. Particle sizes and antigen encapsulating efficiency were then evaluated. After application to bare mouse skin, topical sites were examined for the presence of fluorescence-labeled liposome. The efficacy of the transcutaneously delivered OVA-loaded flexible liposome in activating the immune responses was investigated by detecting serum immunoglobulin G levels. The influence of an adjuvant, imiquimod, in the transcutaneous immunization was also tested.Results: Two flexible liposomes with well-encapsulated OVA were successfully prepared by film-dispersion or reverse-phase evaporation methods. The sizes of the prepared flexible liposomes ranged from 200 to 400 nm. In vivo, the fluorescence-labeled liposome was detected in hair-follicle ducts, indicating that the flexible liposome can penetrate the skin barrier through the hair

  18. Complexes containing cationic and anionic pH-sensitive liposomes: comparative study of factors influencing plasmid DNA gene delivery to tumors

    Directory of Open Access Journals (Sweden)

    Chen Y

    2013-04-01

    Full Text Available Yan Chen,* Ji Sun,* Ying Lu, Chun Tao, Jingbin Huang, He Zhang, Yuan Yu, Hao Zou, Jing Gao, Yanqiang Zhong Department of Pharmaceutical Science, School of Pharmacy, The Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: pH-sensitive liposomes represent an effective gene vector in cancer therapy. However, their use is greatly hampered by their relatively low transfection efficiency. To improve the transfection efficiency of pH-sensitive liposomes, we prepared complexes containing 3β-[N-(N',N'-dimethylaminoethane carbamoyl] cholesterol (DC-Chol and dioleoylphosphatidyl ethanolamine (DOPE liposomes and pH-sensitive liposomes composed of cholesteryl hemisuccinate (CHEMS and DOPE, and evaluated the influence of various factors on plasmid DNA (pDNA transfection efficiency. All DC-Chol/DOPE liposome/pDNA and pH-sensitive liposome complexes showed similarly potent pH sensitivity. In the presence of serum-containing medium, two optimized complexes of DC-Chol/DOPE liposomes/pDNA and pH-sensitive PEGylated liposomes showed high transfection efficiency of 22.94% and 20.07%, respectively. Notably, DC-Chol/DOPE (2:3 liposomes/pH-sensitive PEGylated (1% liposome complexes with a charge ratio of 1:1 (m/m [+/-] showed enhanced accumulation in tumors in vivo. Our results show the influence of various factors on pDNA transfection efficiency in complexes of DC-Chol/DOPE liposomes and pH-sensitive PEGylated liposomes. Understanding of such mechanisms will lead to better design of complexes of DC-Chol/DOPE liposomes and pH-sensitive liposomes for gene therapy. Keywords: cationic liposomes, pH-sensitive liposomes, pDNA, transfection, PEGylated

  19. CELECOXIB LOADED LIPOSOMES: DEVELOPMENT, CHARACTERIZATION AND IN VITRO EVALUATION

    Directory of Open Access Journals (Sweden)

    M. Yasmin Begum

    2012-01-01

    Full Text Available CLX (celecoxib is a highly hydrophobic non-steroidal anti-inflammatory drug with high plasma protein binding. We describe here the encapsulation of CLX in MLVs composed of SPC and variable amounts of cholesterol. The influence of drug – lipid ratio was studied and amount of the drug could be encapsulated was optimized. The effect of cholesterol and other process parameters were studied to obtain the liposomal vesicles with desired quality. All the prepared formulations were characterized for their physico chemical properties such as appearance, vesicle size, vesicle size distribution and percentage drug entrapment. Stability of the liposomes in terms of their drug leakage and drug retention behaviour was studied by storing the liposomal formulations under different conditions for the period of 30 days. The optimized formulation parameters and process parameters resulted the liposomes with mean vesicle diameter of 4.81μ. The maximum percentage drug entrapment was achieved with the formulation CL3 which contains the drug – lipid ratio of 1:10%W/W and the percentage drug entrapment is equal to 72.33±0.64 (%. In vitro release data showed that release profile follows zero order kinetics. Celecoxib liposomes with good stability and appreciable controlled drug release with good retention of the drug even after 24 hours were prepared successfully.

  20. Optimization and modeling of the remote loading of luciferin into liposomes.

    Science.gov (United States)

    Hansen, Anders Højgaard; Lomholt, Michael A; Hansen, Per Lyngs; Mouritsen, Ole G; Arouri, Ahmad

    2016-07-11

    We carried out a mechanistic study to characterize and optimize the remote loading of luciferin into preformed liposomes of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPC/DPPG) 7:3 mixtures. The influence of the loading agent (acetate, propionate, butyrate), the metal counterion (Na(+), K(+), Ca(+2), Mg(+2)), and the initial extra-liposomal amount of luciferin (nL(add)) on the luciferin Loading Efficiency (LE%) and luciferin-to-lipid weight ratio, i.e., Loading Capacity (LC), in the final formulation was determined. In addition, the effect of the loading process on the colloidal stability and phase behavior of the liposomes was monitored. Based on our experimental results, a theoretical model was developed to describe the course of luciferin remote loading. It was found that the highest luciferin loading was obtained with magnesium acetate. The use of longer aliphatic carboxylates or inorganic proton donors pronouncedly reduced luciferin loading, whereas the effect of the counterion was modest. The remote-loading process barely affected the colloidal stability and drug retention of the liposomes, albeit with moderate luciferin-induced membrane perturbations. The correlation between luciferin loading, expressed as LE% and LC, and nL(add) was established, and under our conditions the maximum LC was attained using an nL(add) of around 2.6μmol. Higher amounts of luciferin tend to pronouncedly perturb the liposome stability and luciferin retention. Our theoretical model furnishes a fair quantitative description of the correlation between nL(add) and luciferin loading, and a membrane permeability coefficient for uncharged luciferin of 1×10(-8)cm/s could be determined. We believe that our study will prove very useful to optimize the remote-loading strategies of moderately polar carboxylic acid drugs in general. PMID:27163524

  1. Quick-and-easy preparation and purification of quantum dot-loaded liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Morten B.; Emmerik, Clara van [Radboud University Nijmegen, Department of Organic Chemistry, Institute for Molecules and Materials (Netherlands); Gaal, Ethlinn van; Storm, Gert [Utrecht University, Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences (Netherlands); Hest, Jan C. M. van; Loewik, Dennis W. P. M., E-mail: d.lowik@science.ru.nl [Radboud University Nijmegen, Department of Organic Chemistry, Institute for Molecules and Materials (Netherlands)

    2013-01-15

    Quantum dots are very attractive as fluorescent markers because of their excellent optical properties. For this reason, they have also been used to label liposomes by means of encapsulation, though their feasibility as liposome labels is often hampered by the presence of unencapsulated quantum dots. Until now, laborious gradient ultracentrifugation or less efficient size exclusion chromatography has been the methods of choice to remove unencapsulated quantum dots. Of these two strategies, size exclusion chromatography is most commonly used, despite the known poor separation. Consequently, this prompts for a choice between purification methods yielding high-purity quantum dot-loaded liposomes but low yields or vice versa. Herein, we present a novel high-yield and high-purity methodology to remove unencapsulated quantum dots in a quick and efficient manner based on electrostatic binding of quantum dots to ion-exchange beads. This was accomplished either by means of short column chromatography or via a simple pull-down approach. The purification efficiency was easily assessed via analytical gel electrophoresis, and by copper-mediated quenching of quantum dot fluorescence, it was established that the quantum dots were not adhered to the liposomes but encapsulated inside these. Furthermore, the recovery degree of quantum dot-loaded liposomes after ion-exchange purification was found to be excellent compared with size exclusion chromatography. Lastly, a method is presented to quantify the number of quantum dots encapsulated in the liposomes by the combined efforts of particle counting and inductively coupled plasma mass spectrometry.

  2. Design and characterization of anionic PEGylated liposomal formulation loaded with paclitax for ovarian cancer

    Directory of Open Access Journals (Sweden)

    K Makwana

    2012-01-01

    Full Text Available Despite its strong antitumor activity, paclitaxel (Taxol® has limited clinical applications due to its low aqueous solubility and hypersensitivity caused by cremophor EL and ethanol which is the vehicle used in the current commercial product. In an attempt to develop a pharmaceutically acceptable formulation that could replace Taxol® , we have prepared PEGylated liposomes containing paclitaxel to improve its solubility and physicochemical stability. Its percent drug entrapment (PDE, mean particle size, zeta potential and in vitro release profile were determined. The optimized PEGylated liposomes provided high percent entrapment efficiency (64.29% and mean particle size of 228.6 nm. The electroflocculation method showed 5 mol% of DSPE-mPEG2000 was required to obtain maximum stability for PEGylated liposome. In vitro release data showed its long circulating characteristic. Paclitaxel loaded PEGylated liposomes can be considered a promising long circulating paclitaxel delivery with absence of side effects related to Taxol® .

  3. Preparation and physicochemical characterization of topical chitosan-based film containing griseofulvin-loaded liposomes

    Science.gov (United States)

    Bavarsad, Neda; Kouchak, Maryam; Mohamadipour, Pardis; Sadeghi-Nejad, Batool

    2016-01-01

    Griseofulvin is an antifungal drug and is available as oral dosage forms. Development of topical treatment could be advantageous for superficial fungal infections of the skin. In this study, films prepared from the incorporation of griseofulvin-loaded liposomes in chitosan film for topical drug delivery in superficial fungal infections. The properties of the films were characterized regarding mechanical properties, swelling, ability to transmit vapor, drug release, thermal behavior, and antifungal efficacy against Microsporum gypseum and Epidermophyton floccosum. The presence of liposomes led to decreased mechanical properties but lower swelling ratio. Higher amount of drug permeation and rate of flux were obtained by liposomes incorporated in films compared to liposomal formulations. Antifungal efficacy of formulations was confirmed against two species of dermatophytes in vitro. Therefore, two concepts of using vesicular carrier systems and biopolymeric films have been combined and this topical novel composite film has the potential for griseofulvin delivery to superficial fungal infections. PMID:27429928

  4. Glycyl-L-Histidyl-L-Liysine-Cu(2+ loaded liposome formulations

    Directory of Open Access Journals (Sweden)

    Setenay Erdem

    2010-05-01

    Full Text Available Enhancement of collagen synthesis by glycyl-l-histidyl-l-lysine-Cu2+ (GHK-Cu derivatives is well known. The different activities of GHK-Cu would be of interest for cosmetic applications. Liposomes provide many benefits as topical drug delivery systems. Structure of double layer and lipid composition of liposomes keep the active substance longer in skin and provide regularly release to the deeper skin layers. Our aim in this study was to prepare GHK-Cu loaded liposomes and characterize them to use in a cosmetic formulation. UV spectrophotometric method was used to detect the GHK-Cu in aqueous medium and FTIR spectrums were taken to determine the absorption bands. In stability studies, it was observed that aqueous solutions of GHK-Cu samples maintained their stability at 4oC for 4 months and the FTIR absorption bands of powdered GHK-Cu did not change when stored under the same stability conditions with aqueous samples. Different liposome formulations were prepared by lipid film hydration technique using different kinds of phospholipids (dipalmitoylphosphatidylcholine (DPPC-5911, Epicuron 100H, and Epicuron 200SH. The particle size and shape of liposomes were determined using microscope, SEM, and laser diffraction method. The average particle size was found to be 13μm. In the percent entrapment studies of GHK-Cu in liposomes, it was found that the highest entrapment was achieved with the liposomes prepared with Epicuron 100H. It was concluded that diffusion of GHK-Cu from liposomes prepared with Epicuron 100H was higher and more steady than that of liposomes prepared with DPPC and Epicuron 200SH in diffusion studies where a dialysis tubing was used.

  5. 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

  6. Cationic liposome-nucleic acid nanoparticle assemblies with applications in gene delivery and gene silencing.

    Science.gov (United States)

    Majzoub, Ramsey N; Ewert, Kai K; Safinya, Cyrus R

    2016-07-28

    Cationic liposomes (CLs) are synthetic carriers of nucleic acids in gene delivery and gene silencing therapeutics. The introduction will describe the structures of distinct liquid crystalline phases of CL-nucleic acid complexes, which were revealed in earlier synchrotron small-angle X-ray scattering experiments. When mixed with plasmid DNA, CLs containing lipids with distinct shapes spontaneously undergo topological transitions into self-assembled lamellar, inverse hexagonal, and hexagonal CL-DNA phases. CLs containing cubic phase lipids are observed to readily mix with short interfering RNA (siRNA) molecules creating double gyroid CL-siRNA phases for gene silencing. Custom synthesis of multivalent lipids and a range of novel polyethylene glycol (PEG)-lipids with attached targeting ligands and hydrolysable moieties have led to functionalized equilibrium nanoparticles (NPs) optimized for cell targeting, uptake or endosomal escape. Very recent experiments are described with surface-functionalized PEGylated CL-DNA NPs, including fluorescence microscopy colocalization with members of the Rab family of GTPases, which directly reveal interactions with cell membranes and NP pathways. In vitro optimization of CL-DNA and CL-siRNA NPs with relevant primary cancer cells is expected to impact nucleic acid therapeutics in vivoThis article is part of the themed issue 'Soft interfacial materials: from fundamentals to formulation'. PMID:27298431

  7. Nonviral Gene Delivery to Mesenchymal Stem Cells Using Cationic Liposomes for Gene and Cell Therapy

    Directory of Open Access Journals (Sweden)

    C. Madeira

    2010-01-01

    Full Text Available Mesenchymal stem cells (MSCs hold a great promise for application in several therapies due to their unique biological characteristics. In order to harness their full potential in cell-or gene-based therapies it might be advantageous to enhance some of their features through gene delivery strategies. Accordingly, we are interested in developing an efficient and safe methodology to genetically engineer human bone marrow MSC (BM MSC, enhancing their therapeutic efficacy in Regenerative Medicine. The plasmid DNA delivery was optimized using a cationic liposome-based reagent. Transfection efficiencies ranged from ~2% to ~35%, resulting from using a Lipid/DNA ratio of 1.25 with a transgene expression of 7 days. Importantly, the number of plasmid copies in different cell passages was quantified for the first time and ~20,000 plasmid copies/cell were obtained independently of cell passage. As transfected MSC have shown high viabilities (>90% and recoveries (>52% while maintaining their multipotency, this might be an advantageous transfection strategy when the goal is to express a therapeutic gene in a safe and transient way.

  8. Terbinafine hydrochloride loaded liposome film formulation for treatment of onychomycosis: in vitro and in vivo evaluation.

    Science.gov (United States)

    Tuncay Tanrıverdi, Sakine; Hilmioğlu Polat, Süleyha; Yeşim Metin, Dilek; Kandiloğlu, Gülşen; Özer, Özgen

    2016-06-01

    Onychomycosis is a fungal infection of nail unit that is caused by dermatophytes. Oral Terbinafine hydrochloride (TBF-HCl) is being used for the treatment of onychomycosis since 24 years. The side effects caused by the systemic application and limitations of topical administration of this drug regarding the diffusion through nail lead to the development of a new formulation based on, TBF-HCl-loaded liposome. The newly obtained film formulations were prepared and characterized via several parameters, such as physical appearance, drug content, thickness, bioadhesive properties and tensile strength. In vitro and ex vivo permeation studies were performed to select an optimum film formulation for antifungal activity to show the efficiency of formulations regarding the treatment of onychomycosis. The in vitro release percentages of drug were found 71.6 ± 3.28, 54.4 ± 4.26, 56.1 ± 7.48 and 46.0 ± 2.43 for liposome loaded pullulan films (LI-P, LII-P) and liposome loaded Eudragit films (LI-E, LII-E), respectively. The accumulated drug in the nail plates were found 31.16 ± 4.22, 24.81 ± 5.35, 8.17 ± 1.81 and 8.92 ± 3.37 for LI-P, LII-P, LI-E and LII-E, respectively, which within therapeutic range for all film formulations. The accumulated drug in the nail plate was found within therapeutic range for all film formulations. The efficacy of the selected TBF-HCl-loaded liposome film formulation was compared with TBF-HCl-loaded liposome, ethosome, liposome poloxamer gel and ethosome chitosan gel formulations. It was found that TBF-HCl-loaded liposome film formulation had better antifungal activity on fungal nails which make this liposome film formulation promising for ungual therapy of fungal nail infection. PMID:26226352

  9. 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

  10. Utilization of thin film method for preparation of celecoxib loaded liposomes

    Directory of Open Access Journals (Sweden)

    Eskandar Moghimipour

    2012-06-01

    Full Text Available Purpose: Celecoxib is nonsteroiddal anti-inflammatory drug that has been used extensively to treat patients with arthritis. The aim of the present study was to formulate and characterize liposomal vesicles loaded with celecoxib. Methods: Liposomes were prepared by thin film method using soya lecithin and cholesterol. The release of drug was determined using a dialysis membrane method. Liposomes were characterized by Differential Scanning Calorimetery (DSC, Transmission Electron Microscopy (TEM and their particle size was also determined. Results: The results showed that the drug encapsulation efficiency was 67.34% and there was 67.16% release after 0.5, 1, 2, 3, 4, 5, 6, 7, 8 and 24 h. Results of particle size determination showed a mean size of 677nm and nanoparticles were spherical as shown by TEM. The DSC curve of lecithin, cholesterol and celecoxib were different from celecoxib containing liposome. Conclusion: The results of characterization of the vesicles indicated the potential application of celecoxib loaded liposome as carrier system.

  11. Non-ionic surfactant modified cationic liposomes mediated gene transfection in vitro and in the mouse lung.

    Science.gov (United States)

    Ding, Wuxiao; Izumisawa, Tomohiro; Hattori, Yoshiyuki; Qi, Xianrong; Kitamoto, Dai; Maitani, Yoshie

    2009-02-01

    As reported previously, cationic liposomes formulated with dioleoylphosphatidylethanolamine (DOPE) and N,N-methyl hydroxyethyl aminopropane carbamoyl cholesterol (MHAPC-liposomes) achieved efficient gene transfection in the mouse lung following intratracheal injection. We have studied here the role of surfactants, mannosylerythritol lipid-A (MEL-A) and polysorbate 80 (Tween 80), in affecting gene transfection of MHAPC-lipoplexes (complex with pCMV-luc DNA) in A549 cells and in the mouse lung. MEL-A increased gene transfection of MHAPC-lipoplexes significantly in vitro and slightly in the mouse lung, while Tween 80 decreased it both in vitro and in vivo. As assessed by confocal laser scanning microscopy and fluorescence imaging, MEL-A might faciliate gene dissociation from MHAPC-lipoplexes with fluorescein-labeled oligodeoxynucleotide (FITC-ODN) after internalization into the cells and retained the lipoplexes in the mouse lung for prolonged time, while Tween 80 was inefficient to deliver foreign gene into target cells and in the lung. These results demonstrated that MEL-A is advantageous to Tween 80 in the modification of cationic liposomes as gene delivery vectors in the lung. PMID:19182397

  12. Liposome size and charge optimization for intraarterial delivery to gliomas.

    Science.gov (United States)

    Joshi, Shailendra; Cooke, Johann R N; Chan, Darren K W; Ellis, Jason A; Hossain, Shaolie S; Singh-Moon, Rajinder P; Wang, Mei; Bigio, Irving J; Bruce, Jeffrey N; Straubinger, Robert M

    2016-06-01

    Nanoparticles such as liposomes may be used as drug delivery vehicles for brain tumor therapy. Particle geometry and electrostatic properties have been hypothesized to be important determinants of effective tumor targeting after intraarterial injection. In this study, we investigate the combined roles of liposome size and surface charge on the effectiveness of delivery to gliomas after intraarterial injection. Intracarotid injection of liposomes was performed in separate cohorts of both healthy and C6 glioma-bearing Sprague Dawley rats after induction of transient cerebral hypoperfusion. Large (200 nm) and small (60-80 nm) fluorescent dye-loaded liposomes that were either cationic or neutral in surface charge were utilized. Delivery effectiveness was quantitatively measured both with real-time, in vivo and postmortem diffuse reflectance spectroscopy. Semi-quantitative multispectral fluorescence imaging was also utilized to assess the pattern and extent of liposome targeting within tumors. Large cationic liposomes demonstrated the most effective hemispheric and glioma targeting of all the liposomes tested. Selective large cationic liposome retention at the site of glioma growth was observed. The liposome deposition pattern within tumors after intraarterial injection was variable with both core penetration and peripheral deposition observed in specific tumors. This study provides evidence that liposome size and charge are important determinants of effective brain and glioma targeting after intraarterial injection. Our results support the future development of 200-nm cationic liposomal formulations of candidate intraarterial anti-glioma agents for further pre-clinical testing. PMID:27091339

  13. Sucrose ester based cationic liposomes as effective non-viral gene vectors for gene delivery.

    Science.gov (United States)

    Zhao, Yinan; Zhu, Jie; Zhou, Hengjun; Guo, Xin; Tian, Tian; Cui, Shaohui; Zhen, Yuhong; Zhang, Shubiao; Xu, Yuhong

    2016-09-01

    As sucrose esters (SEs) are natural and biodegradable excipients with excellent drug dissolution and drug absorption/permeation in controlled release systems, we firstly incorporated SE into liposomes for gene delivery in this article. A peptide-based lipid (CDO14), Gemini-based quaternary ammonium-based lipid (CTA14), and mono-head quaternary ammonium lipid (CPA14), and SE as helper lipid, were prepared into liposomes which could enhance the interactions between liposomes and pDNA. Most importantly, the liposomes with helper lipid SE showed higher transfection and lower cytotoxicity than those without SE in Hela and A549 cells. It was also found that the transfection efficiency increased with the increase of SE content. The selected liposome, CDO14/SE, was able to deliver siRNA against luciferase for silencing gene in lung tumors of mice, with little in vivo toxicity. The results convincingly demonstrated SEs could be highly desirable candidates for gene delivery systems. PMID:27232309

  14. The Effects of Salt on the Physicochemical Properties and Immunogenicity of Protein Based Vaccine Formulated in Cationic Liposome

    OpenAIRE

    Yan, Weili; Huang, Leaf

    2008-01-01

    Recently, we have developed a simple and potent therapeutic cancer vaccine consisting of a cationic lipid and a peptide antigen. In this report, we expanded the utility of this formulation to a protein based vaccine. First, we formulated the human papillomavirus (HPV) 16 E7 protein (E7) in different doses of DOTAP liposome. The results showed that these formulations failed to regress an established tumor. However, when sodium chloride (30 mM) was added to the DOTAP (100 nmol) / E7 (20 μg) for...

  15. Double-loaded liposomes encapsulating Quercetin and Quercetin beta-cyclodextrin complexes: Preparation, characterization and evaluation

    Directory of Open Access Journals (Sweden)

    Jessy Shaji

    2012-01-01

    Full Text Available Beta-cyclodextrin (CD inclusion complexes of Quercetin were formed and characterized by Differential scanning calorimetry (DSC and Fourier transform infra-red spectroscopy (FTIR spectroscopy. Plain Quercetin liposomes using phosphatidylcholine and cholesterol were prepared and optimized. Factors such as ratio of lipids employed, drug:lipid ratio, etc. were fine tuned and optimized to achieve maximum entrapment of the Quercetin into the bilayer. Entrapment was further enhanced by double loading the liposomes. These were prepared by incorporating Quercetin as a plain drug as well as the inclusion complexes within the lipid bilayer and the aqueous compartment, respectively, of the liposomes using the thin film hydration technique. The highest entrapment was achieved with a lipid ratio of 9:1, and the amount of plain drug entering the bilayer was 1/10 th the amount of lipid employed. Double loading increased this value to one part of drug per five parts of lipid when Quercetin-beta-CD (1:1 mol/mol was entrapped. The release of Quercetin from liposomes was highest when the drug was entrapped in the form of a complex with beta cylodextrin. The high entrapment ability of Quercetin in the form of plain drug as well as beta cylodextrin-Quercetin complexes in comparison with plain drug is an indubitable advantage of this approach.

  16. pH-Sensitive carboxymethyl chitosan-modified cationic liposomes for sorafenib and siRNA co-delivery

    Directory of Open Access Journals (Sweden)

    Yao Y

    2015-10-01

    Full Text Available Yao Yao, Zhihui Su, Yanchao Liang, Na Zhang School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, People’s Republic of China Abstract: Combination of chemotherapeutic drug and small interfering RNA (siRNA can affect multiple disease pathways and has been proven effective in suppressing tumor progression. Co-delivery of drug and siRNA within a same nanocarrier is a vital means in this field. The present study aimed at the development of a pH-sensitive liposome to co-deliver drug and siRNA to tumor region. Driven by the electrostatic interaction, the pH-sensitive material, carboxymethyl chitosan (CMCS, was coated onto the surface of the cationic liposome (CL preloaded with sorafenib (Sf and siRNA (Si. To evaluate whether the resulting CMCS-modified Sf and siRNA co-delivery cationic liposome (CMCS-SiSf-CL enhanced antitumor efficiency after systematic administration, in vitro and in vivo experiments were evaluated in HepG2 cells and the H22 cells-bearing Kunming mice model. The experimental results demonstrated that CMCS-SiSf-CL was able to condense siRNA efficiently and protect siRNA from being degraded by serum and RNase. The release rate of Sf from CMCS-modified liposome exhibited pH-sensitive release behavior. Furthermore, in vitro cellular uptake results showed that CMCS-SiSf-CL yielded higher fluorescence intensity at pH 6.5 than at pH 7.4, and that siRNA could be delivered to tumor site by CMCS-SiSf-CL in vivo. The in vivo antitumor efficacy showed that CMCS-Sf-CL inhibits tumor growth effectively when compared with free Sf solution. In current experimental conditions, this liposomal formulation did not show significant toxicity both in vitro and in vivo. Therefore, co-delivering Sf with siRNA by CMCS-SiSf-CL might provide a promising approach for tumor therapy. Keywords: co-delivery, sorafenib, gene, charge conversion, cancer therapy

  17. Phospholipid liposomes acquire apolipoprotein E in atherogenic plasma and block cholesterol loading of cultured macrophages.

    OpenAIRE

    Williams, K J; Tall, A.R.; Bisgaier, C; Brocia, R

    1987-01-01

    A single infusion of phospholipid liposomes promptly and persistently abolished the ability of hypercholesterolemic rabbit plasma to cause cholesteryl ester loading in cultured macrophages. This phospholipid enrichment of plasma caused moderate stimulation of cellular cholesterol efflux and, unexpectedly, almost complete inhibition of cellular uptake of beta-very low density lipoprotein (beta-VLDL), the major cholesteryl ester-rich particle in hypercholesterolemic rabbit plasma. Cell viabilit...

  18. Effect of the preparation procedure on the structural properties of oligonucleotide/cationic liposome complexes (lipoplexes) studied by electron spin resonance and Zeta potential.

    Science.gov (United States)

    Ciani, Laura; Ristori, Sandra; Bonechi, Claudia; Rossi, Claudio; Martini, Giacomo

    2007-12-01

    Lipoplexes with different surface charge were prepared from a short oligonucleotide (20 mer, dsAT) inserted into liposomes of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phospho-ethanolamine (DOPE). The starting liposomes were prepared by two different procedures, i.e. progressive dsAT addition starting from plain liposomes (titration) and direct mixing of dsAT with pure liposomes (point to point preparation). Lipoplexes were characterized from a molecular point of view by Electron Spin Resonance (ESR) of a cationic spin probe and by Nuclear Magnetic Resonance. Structural and surface features were analysed by Zeta potential (zeta) measurements and Cryo-TEM micrographs. The complete set of results allowed to demonstrate that: i) the interactions between dsAT and cationic lipids were strong and occurred at the liposome surface; ii) the overall shape and physicochemical properties of liposomes did not change when short nucleic acid fragments were added before surface charge neutralization; iii) the bilayer structure of the lipids in lipoplexes was substantially preserved at all charge ratios; iv) the physical status of lipoplexes with electrical charge far from neutrality did not depend on the preparation method. PMID:17950520

  19. Enhanced non-inflammasome mediated immune responses by mannosylated zwitterionic-based cationic liposomes for HIV DNA vaccines.

    Science.gov (United States)

    Qiao, Chenmeng; Liu, Jiandong; Yang, Jun; Li, Yan; Weng, Jie; Shao, Yiming; Zhang, Xin

    2016-04-01

    Human immunodeficiency virus (HIV) DNA vaccine can induce cellular and humoral immunity. A safe and effective HIV DNA vaccine is urgent need to prevent the spread of acquired immune deficiency syndrome (AIDS). The major drawback of DNA vaccines is the low immunogenicity, which is caused by the poor delivery to antigen presenting cells and insufficient antigen expression. Sparked by the capability of endosomal/lysosomal escape of the zwitterionic lipid distearoyl phosphoethanol-amine-polycarboxybetaine (DSPE-PCB), we attempted to develop a zwitterionic-based cationic liposome with enhanced immunogenicity of DNA vaccines. The mannosylated zwitterionic-based cationic liposome (man-ZCL) was constructed as a DNA vaccine adjuvant for HIV vaccination. Man-ZCL could complex with DNA antigens to form a tight structure and protect them from nuclei enzyme degradation. Benefited from the capability of the specific mannose receptor mediated antigen processing cells targeting and enhanced endosomal/lysosomal escape, the man-ZCL lipoplexes were supposed to promote antigen presentation and the immunogenicity of DNA vaccines. In vitro and in vivo results revealed that man-ZCL lipoplexes showed enhanced anti-HIV immune responses and lower toxicity compared with CpG/DNA and Lipo2k/DNA, and triggered a Th1/Th2 mixed immunity. An antigen-depot effect was observed in the administration site, and this resulted in enhanced retention of DNA antigens in draining lymph nodes. Most importantly, the man-ZCL could assist to activate T cells through a non-inflammasome pathway. These findings suggested that the man-ZCL could be potentially applied as a safe and efficient DNA adjuvant for HIV vaccines. PMID:26851653

  20. 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.

  1. The Effectiveness of Raloxifene-Loaded Liposomes and Cochleates in Breast Cancer Therapy.

    Science.gov (United States)

    Ağardan, N Başaran Mutlu; Değim, Zelihagül; Yılmaz, Şükran; Altıntaş, Levent; Topal, Turgut

    2016-08-01

    Liposome (spherical vesicles) and cochleate (multilayer crystalline, spiral structure) formulations containing raloxifene have been developed having dimethyl-β-cyclodextrin (DM-β-CD) or sodium taurocholate (NaTC). Raloxifene was approved initially for the treatment of osteoporosis but it is also effective on breast tissue and endometrial cells. Raloxifene inhibits matrix metalloproteinase-2 (MMP-2) enzyme, which is known to be responsible for tumor invasion and the initiation of angiogenesis during the tumor growth. Therefore, raloxifene was selected as a model drug. A series of raloxifene-loaded liposome and cochleate formulations were prepared. In vitro release studies and in vivo tests were performed. Breast cancer cell lines (MCF-7) were also used to find the most effective formulation. Highest antitumor activity was observed, and MMP-2 enzyme was also found to be inhibited with raloxifene-loaded cochleates containing DM-β-CD. These developed formulations can be helpful for further treatment alternatives and new strategies for cancer therapy. PMID:26729527

  2. Enhanced antimicrobial activity of nisin-loaded liposomal nanoparticles against foodborne pathogens.

    Science.gov (United States)

    Zou, Yunyun; Lee, Hyeon-Yong; Seo, Yong-Chang; Ahn, Juhee

    2012-03-01

    This study was designed to evaluate the prolonged antimicrobial stability of nisin-loaded liposome (LipoN) nanoparticles against Listeria monocytogenes and Staphylococcus aureus. The sizes of bare liposomes and LipoN were uniformly distributed between 114 and 125 nm. The nanoparticles were homogeneously dispersed in water with less than 0.2 of polydispersity index. The zeta potential value of LipoN was +17.1 mV due to the positive charged nisin, attaining 70% of loading efficiency. The minimum inhibitory concentration of LipoN against L. monocytogenes and S. aureus was 320 international unit/mL. The LipoN significantly enhanced the antimicrobial stability in brain heart infusion agar compared to free nisin. The numbers of L. monocytogenes and S. aureus exposed to LipoN were effectively reduced by more than 6 log colony-forming unit/mL after 48 and 72 h of incubation, respectively. These results provide useful information for the development of antimicrobial delivery system to improve food safety. PMID:22329855

  3. 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

  4. Cholesterol Derivatives Based Charged Liposomes for Doxorubicin Delivery: Preparation, In Vitro and In Vivo Characterization

    Directory of Open Access Journals (Sweden)

    Yu Nie, Li Ji, Hong Ding, Li Xie, Li Li, Bin He, Yao Wu, Zhongwei Gu

    2012-01-01

    Full Text Available Cholesterol plays a critical role in liposome composition. It has great impact on the behavior of liposome in vitro and in vivo. In order to verify the possible effects from cholesterol charge, surface shielding and chemical nature, two catalogs of liposomes with charged and PEGylated cholesterols were synthesized. Anionic liposomes (AL and cationic liposomes (CL were prepared, with charges from hemisuccinate and lysine in cholesterol derivatives, respectively. Characteristics of different formulated liposomes were investigated after doxorubicin encapsulation, using neutral liposomes (NL as control. Results showed that after PEGylation, AL and CL liposomes displayed prolonged retention release profile, while kept similar size distribution, encapsulation efficiency, low cytotoxicity and hemolysis comparing with NL. Confocal laser scanning microscopy and flow cytometry experiments confirmed the significantly higher cell uptake from AL and CL vesicles than the NL in mouse breast carcinoma and melanoma cells, human epithelial carcinoma and hepatoma cells. It was in accordance with our corresponding cellular mortality studies of DOX-loaded liposomes. The in vivo anti-tumor effect experiments from charged liposomes also presented much higher tumor inhibition effect (70% vs 45%, p < 0.05 than NL liposomes. This is the first time reporting anti-cancer effect from charged cholesterol liposome with/without PEGylation. It may give deeper understanding on the liposome formulation which is critical for liposome associated drug research and development.

  5. Co-loaded paclitaxel/rapamycin liposomes: Development, characterization and in vitro and in vivo evaluation for breast cancer therapy.

    Science.gov (United States)

    Eloy, Josimar O; Petrilli, Raquel; Topan, José Fernando; Antonio, Heriton Marcelo Ribeiro; Barcellos, Juliana Palma Abriata; Chesca, Deise L; Serafini, Luciano Neder; Tiezzi, Daniel G; Lee, Robert J; Marchetti, Juliana Maldonado

    2016-05-01

    Paclitaxel and rapamycin have been reported to act synergistically to treat breast cancer. Albeit paclitaxel is available for breast cancer treatment, the most commonly used formulation in the clinic presents side effects, limiting its use. Furthermore, both drugs present pharmacokinetics drawbacks limiting their in vivo efficacy and clinic combination. As an alternative, drug delivery systems, particularly liposomes, emerge as an option for drug combination, able to simultaneously deliver co-loaded drugs with improved therapeutic index. Therefore, the purpose of this study is to develop and characterize a co-loaded paclitaxel and rapamycin liposome and evaluate it for breast cancer efficacy both in vitro and in vivo. Results showed that a SPC/Chol/DSPE-PEG (2000) liposome was able to co-encapsulate paclitaxel and rapamycin with suitable encapsulation efficiency values, nanometric particle size, low polydispersity and neutral zeta potential. Taken together, FTIR and thermal analysis evidenced drug conversion to the more bioavailable molecular and amorphous forms, respectively, for paclitaxel and rapamycin. The pegylated liposome exhibited excellent colloidal stability and was able to retain drugs encapsulated, which were released in a slow and sustained fashion. Liposomes were more cytotoxic to 4T1 breast cancer cell line than the free drugs and drugs acted synergistically, particularly when co-loaded. Finally, in vivo therapeutic evaluation carried out in 4T1-tumor-bearing mice confirmed the in vitro results. The co-loaded paclitaxel/rapamycin pegylated liposome better controlled tumor growth compared to the solution. Therefore, we expect that the formulation developed herein might be a contribution for future studies focusing on the clinical combination of paclitaxel and rapamycin. PMID:26836480

  6. A novel approach for lung delivery of rifampicin-loaded liposomes in dry powder form for the treatment of tuberculosis

    Directory of Open Access Journals (Sweden)

    Jagadevappa S Patil

    2015-01-01

    Full Text Available Background: Lung administration of antibiotics by nebulization is promising for improved treatment efficiency for pulmonary infections, as it increases drug concentration at sites of infection while minimizing systemic side effects. For poorly soluble molecules like rifampicin, lipid particulate system may improve lung delivery. Materials and Methods: We investigated rifampicin-loaded freeze-dried liposomes. Various formulations were prepared with different drug lipid ratios and one formulation was optimized. Optimized colloidal liposome formulation was freeze-dried and subsequently subjected for various evaluation and characterization parameters such as in-vitro dissolution, in-vitro antitubercular activity, aerodynamic characters, surface morphology, and thermal behavior. The optimized formulation of rifampicin-loaded freeze-dried liposome and free rifampicin was subjected for the in-vivo drug disposition study in Wister rat model by intra-tracheal instillation in comparison with an oral route of administration. Results: The results of pharmacokinetic study for both free drug and the formulation suggested that liposomes released the drug in a controlled manner for a longer period of time. The enhanced efficiency of drug incorporated into liposomes suggested that the delivery of encapsulated drugs to macrophages was more rapid than that of free drug. Conclusion: Therefore, the pharmacokinetic and drug disposition studies provided a sound basis for predicting the successful treatment for tuberculosis.

  7. Optimization of Fabrication Parameters to Prepare Tea Catechin-Loaded Liposomes using Response Surface Methodology

    Directory of Open Access Journals (Sweden)

    Jianjun Fang

    2013-01-01

    Full Text Available The purpose of this study was to optimize the formulation of tea catechin-loaded nano-liposomes using response surface methodology. Response surface methodology based on central composite rotatable design has been successfully used to model and optimize biochemical and biotechnological processes. The mass ratio of phosphatidylcholine and cholesterol (1-3, catechin concentration (3-5 mg/mL, pH values of phosphate buffer solution (6-7 and the volume ratio of organic phase and aqueous phase (2-4 were selected as independent variables with encapsulation efficiency and particle size as dependent variables. For each response, a second-order polynomial model was developed using multiple linear regression analysis. Applying a desirability function method the optimum parameters were: phosphatidylcholine to cholesterol mass ratio of 2.17, catechin concentration of 5 mg/mL, pH values of phosphate buffer solution of 6.62 and organic phase to aqueous phase volume ratio of 3.05. At this optimum point, particle size and encapsulation efficiency were found to be 220 nm and 60.18%, respectively. Furthermore, leakage ratio of nano-liposomes was used to determine the influence of storage period.

  8. Synthesis of linear and cyclic peptide-PEG-lipids for stabilization and targeting of cationic liposome-DNA complexes.

    Science.gov (United States)

    Ewert, Kai K; Kotamraju, Venkata Ramana; Majzoub, Ramsey N; Steffes, Victoria M; Wonder, Emily A; Teesalu, Tambet; Ruoslahti, Erkki; Safinya, Cyrus R

    2016-03-15

    Because nucleic acids (NAs) have immense potential value as therapeutics, the development of safe and effective synthetic NA vectors continues to attract much attention. In vivo applications of NA vectors require stabilized, nanometer-scale particles, but the commonly used approaches of steric stabilization with a polymer coat (e.g., PEGylation; PEG=poly(ethylene glycol)) interfere with attachment to cells, uptake, and endosomal escape. Conjugation of peptides to PEG-lipids can improve cell attachment and uptake for cationic liposome-DNA (CL-DNA) complexes. We present several synthetic approaches to peptide-PEG-lipids and discuss their merits and drawbacks. A lipid-PEG-amine building block served as the common key intermediate in all synthetic routes. Assembling the entire peptide-PEG-lipid by manual solid phase peptide synthesis (employing a lipid-PEG-carboxylic acid) allowed gram-scale synthesis but is mostly applicable to linear peptides connected via their N-terminus. Conjugation via thiol-maleimide or strain-promoted (copper-free) azide-alkyne cycloaddition chemistry is highly amenable to on-demand preparation of peptide-PEG-lipids, and the appropriate PEG-lipid precursors are available in a single chemical step from the lipid-PEG-amine building block. Azide-alkyne cycloaddition is especially suitable for disulfide-bridged peptides such as iRGD (cyclic CRGDKGPDC). Added at 10 mol% of a cationic/neutral lipid mixture, the peptide-PEG-lipids stabilize the size of CL-DNA complexes. They also affect cell attachment and uptake of nanoparticles in a peptide-dependent manner, thereby providing a platform for preparing stabilized, affinity-targeted CL-DNA nanoparticles. PMID:26874401

  9. 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 s

  10. ATP-loaded Liposomes Effectively Protect Mechanical Functions of the Myocardium from Global Ischemia in an Isolated Rat Heart Model

    OpenAIRE

    Verma, D.D.; Levchenko, T.S.; Bernstein, E.A.; Torchilin, V.P

    2005-01-01

    ATP-loaded liposomes (ATP-L) infused into Langendorff-instrumented isolated rat hearts protect the mechanical functions of the myocardium during ischemia/reperfusion. The left ventricular developed pressure (LVDP) at the end of the reperfusion in the ATP-L group recovered to 72% of the baseline (preservation of the systolic function) compared to 26%, 40%, and 51% in the groups treated with Krebs-Henseleit (KH) buffer, empty liposomes (EL), and free ATP (F-ATP), respectively. The ATP-L-treated...

  11. Development of monodispersed and functional magnetic polymeric liposomes via simple liposome method

    International Nuclear Information System (INIS)

    We are reporting a simple and rapid method to prepare superparamagnetic, controlled size, and monodispersed magnetic cationic polymeric liposomes (MCPL) by octadecyl quaternized carboxymethyl chitosan (OQCMC) and cholesterol. The whole process is only about 25 min with simple thin-film dispersion and solvent evaporation method. Hydrophilic magnetic nanoparticles (LM) and hydrophobic magnetic nanoparticles (BM) can be encapsulated into these cationic polymeric liposomes, simultaneously or respectively. A model hydrophobic drug indomethacin can be successfully filled in MCPL with high drug loading capacity 22%. MCPL encapsulating BM also showed strong DNA (pEGFP) binding ability. Drug-loaded MCPL have a long and controlled sustained release profile by changing the number of polymeric lipid layer. These functional MCPL nanospheres can be allowed to serve as ideal candidates for many biomedical applications.Graphical AbstractA simple and rapid liposome method was reported to prepare superparamagnetic, controlled size, and monodispersed magnetic cationic polymeric liposomes (MCPL) by polymeric surfactant, octadecyl quaternized carboxymethyl chitosan (OQCMC), and cholesterol. Hydrophilic Fe3O4 ferrofluid and hydrophobic magnetic nanoparticles can be encapsulated into these cationic polymeric liposomes, simultaneously or respectively. Hydrophobic drug indomethacin can be encapsulated into this MCPL with high encapsulating efficiency and with controlled release profile by changing the number of polymeric lipid layer.

  12. Development of monodispersed and functional magnetic polymeric liposomes via simple liposome method

    Energy Technology Data Exchange (ETDEWEB)

    Liang Xiaofei; Wang Hanjie [Tianjin University and Tianjin Key Laboratory of Composites and Functional Materials, Institute of Nanobiotechnology, School of Materials Science and Engineering (China); Jiang Xinguo [Fudan University, School of Pharmacy (China); Chang Jin, E-mail: jinchang@tju.edu.c [Tianjin University and Tianjin Key Laboratory of Composites and Functional Materials, Institute of Nanobiotechnology, School of Materials Science and Engineering (China)

    2010-06-15

    We are reporting a simple and rapid method to prepare superparamagnetic, controlled size, and monodispersed magnetic cationic polymeric liposomes (MCPL) by octadecyl quaternized carboxymethyl chitosan (OQCMC) and cholesterol. The whole process is only about 25 min with simple thin-film dispersion and solvent evaporation method. Hydrophilic magnetic nanoparticles (LM) and hydrophobic magnetic nanoparticles (BM) can be encapsulated into these cationic polymeric liposomes, simultaneously or respectively. A model hydrophobic drug indomethacin can be successfully filled in MCPL with high drug loading capacity 22%. MCPL encapsulating BM also showed strong DNA (pEGFP) binding ability. Drug-loaded MCPL have a long and controlled sustained release profile by changing the number of polymeric lipid layer. These functional MCPL nanospheres can be allowed to serve as ideal candidates for many biomedical applications.Graphical AbstractA simple and rapid liposome method was reported to prepare superparamagnetic, controlled size, and monodispersed magnetic cationic polymeric liposomes (MCPL) by polymeric surfactant, octadecyl quaternized carboxymethyl chitosan (OQCMC), and cholesterol. Hydrophilic Fe{sub 3}O{sub 4} ferrofluid and hydrophobic magnetic nanoparticles can be encapsulated into these cationic polymeric liposomes, simultaneously or respectively. Hydrophobic drug indomethacin can be encapsulated into this MCPL with high encapsulating efficiency and with controlled release profile by changing the number of polymeric lipid layer.

  13. Large-scale preparation of clove essential oil and eugenol-loaded liposomes using a membrane contactor and a pilot plant.

    Science.gov (United States)

    Sebaaly, Carine; Greige-Gerges, Hélène; Agusti, Géraldine; Fessi, Hatem; Charcosset, Catherine

    2016-01-01

    Based on our previous study where optimal conditions were defined to encapsulate clove essential oil (CEO) into liposomes at laboratory scale, we scaled-up the preparation of CEO and eugenol (Eug)-loaded liposomes using a membrane contactor (600 mL) and a pilot plant (3 L) based on the principle of ethanol injection method, both equipped with a Shirasu Porous Glass membrane for injection of the organic phase into the aqueous phase. Homogenous, stable, nanometric-sized and multilamellar liposomes with high phospholipid, Eug loading rates and encapsulation efficiency of CEO components were obtained. Saturation of phospholipids and drug concentration in the organic phase may control the liposome stability. Liposomes loaded with other hydrophobic volatile compounds could be prepared at large scale using the ethanol injection method and a membrane for injection. PMID:26099849

  14. 'One-component' ultrathin multilayer films based on poly(vinyl alcohol) as stabilizing coating for phenytoin-loaded liposomes.

    Science.gov (United States)

    Zasada, Katarzyna; Łukasiewicz-Atanasov, Magdalena; Kłysik, Katarzyna; Lewandowska-Łańcucka, Joanna; Gzyl-Malcher, Barbara; Puciul-Malinowska, Agnieszka; Karewicz, Anna; Nowakowska, Maria

    2015-11-01

    Ultrathin "one-component" multilayer polymeric films for potential biomedical applications were designed based on polyvinyl alcohol,-a non-toxic, fully degradable synthetic polymer. Good uniformity of the obtained film and adequate adsorption properties of the polymeric layers were achieved by functional modification of the polymer, which involved synthesis of cationic and anionic derivatives. Synthesized polymers were characterized by FTIR, NMR spectroscopy, dynamic light scattering measurements and elemental analysis. The layer by layer assembly technique was used to build up a multilayer film and this process was followed using UV-Vis spectroscopy and ellipsometry. The morphology and thickness of the obtained multilayered film material was evaluated by atomic force microscopy (AFM). Preliminary studies on the application of the obtained multilayer film for coating of liposomal nanocarriers containing phenytoin, an antiarrhythmic drug, were performed. The coating effectively stabilizes liposomes and the effect increases with an increasing number of deposited layers until the polymeric film reaches the optimal thickness. The obtained release profiles suggest that bilayer-coated liposomes release phenytoin less rapidly than uncoated ones. The cytotoxicity studies performed for all obtained nanocarriers confirmed that none of them has negative effect on cell viability. All of the performed experiments suggest that liposomes coated with ultrathin film obtained from PVA derivatives can be attractive drug nanocarriers. PMID:26253533

  15. Physico-chemical characterisation of cationic DOTAP liposomes as drug delivery system for a hydrophilic decapeptide before and after freeze-drying.

    Science.gov (United States)

    Wieber, Alena; Selzer, Torsten; Kreuter, Jörg

    2012-02-01

    In the present study, positively charged 1,2-dioleoyloxy-3-trimethylammoniumpropane (DOTAP) liposomes as a delivery system for a hydrophilic decapeptide were developed. The main objective was the preparation of a stable, highly loaded, lyophilised formulation to yield the basis for an acceptable shelf life. The influences of addition of cholesterol, pH value, amounts of lipid and peptide, type and amount of sugar-based cryoprotective agent (trehalose and sucrose), and time point for cryoprotector addition as well as the freeze-drying process parameters were investigated. The collapse temperatures of the liposome dispersions in the presence of the disaccharides trehalose and sucrose were determined using a freeze-drying microscope (Lyostat 2). The liposome morphology before freeze-drying was determined by transmission electron microscopy (TEM). The evidence of intact liposomes after freeze-drying was shown by scanning electron microscope (SEM) imaging. In summary, this study demonstrated the successful development of DOTAP liposomes including their lyophilisation as a drug delivery system for small hydrophilic peptides. PMID:22119734

  16. Folate receptor-targeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for H22 hepatocellular carcinoma both in vitro and in vivo.

    Science.gov (United States)

    Liu, Min-Chen; Liu, Lin; Wang, Xia-Rong; Shuai, Wu-Ping; Hu, Ying; Han, Min; Gao, Jian-Qing

    2016-01-01

    The diacid metabolite of norcantharidin (DM-NCTD) is clinically effective against hepatocellular carcinoma (HCC), but is limited by its short half-life and high incidence of adverse effects at high doses. We developed a DM-NCTD-loaded, folic acid (FA)-modified, polyethylene glycolated (DM-NCTD/FA-PEG) liposome system to enhance the targeting effect and antitumor potency for HCC at a moderate dose based on our previous study. The DM-NCTD/FA-PEG liposome system produced liposomes with regular spherical morphology, with mean particle size approximately 200 nm, and an encapsulation efficiency >80%. MTT cytotoxicity assays demonstrated that the DM-NCTD/FA-PEG liposomes showed significantly stronger cytotoxicity effects on the H22 hepatoma cell line than did PEG liposomes without the FA modification (Pkidney was higher than in the normal liposome group. With regard to in vivo antitumor activity, DM-NCTD/FA-PEG liposomes inhibited tumors in H22 tumor-bearing mice better than either free DM-NCTD or DM-NCTD/PEG liposomes (Pnormal mice, as shown by histopathological examination. All these results demonstrate that DM-NCTD-loaded FA-modified liposomes might have potential application for HCC-targeting therapy. PMID:27110110

  17. Indocyanine Green-Loaded Liposomes for Light-Triggered Drug Release.

    Science.gov (United States)

    Lajunen, Tatu; Kontturi, Leena-Stiina; Viitala, Lauri; Manna, Moutusi; Cramariuc, Oana; Róg, Tomasz; Bunker, Alex; Laaksonen, Timo; Viitala, Tapani; Murtomäki, Lasse; Urtti, Arto

    2016-06-01

    Light-triggered drug delivery systems enable site-specific and time-controlled drug release. In previous work, we have achieved this with liposomes containing gold nanoparticles in the aqueous core. Gold nanoparticles absorb near-infrared light and release the energy as heat that increases the permeability of the liposomal bilayer, thus releasing the contents of the liposome. In this work, we replaced the gold nanoparticles with the clinically approved imaging agent indocyanine green (ICG). The ICG liposomes were stable at storage conditions (4-22 °C) and at body temperature, and fast near-infrared (IR) light-triggered drug release was achieved with optimized phospholipid composition and a 1:50 ICG-to-lipid molar ratio. Encapsulated small molecular calcein and FITC-dextran (up to 20 kDa) were completely released from the liposomes after light exposure for 15 s. Location of ICG in the PEG layer of the liposomes was simulated with molecular dynamics. ICG has important benefits as a light-triggering agent in liposomes: fast content release, improved stability, improved possibility of liposomal size control, regulatory approval to use in humans, and the possibility of imaging the in vivo location of the liposomes based on the fluorescence of ICG. Near-infrared light used as a triggering mechanism has good tissue penetration and safety. Thus, ICG liposomes are an attractive option for light-controlled and efficient delivery of small and large drug molecules. PMID:27097108

  18. Formulation Optimization of Asiaticoside Cationic Liposomes by Using Central Composite Design-response Surface Method%星点设计-响应面法优化积雪草苷阳离子脂质体的处方Δ

    Institute of Scientific and Technical Information of China (English)

    任翔; 刘琨; 张莉

    2016-01-01

    OBJECTIVE:To optimize the formulation of Asiaticoside cationic liposomes,and to investigate the characteristics of drug release in vitro. METHODS:The thin film dispersion method was used to prepare liposome;using encapsulation efficiency and drug-loading amount as index,the formulation of Asiaticoside liposomes was optimized by central composite design-response surface method with the ratio of drug to lipid(X1),the ratio of cholesterol to lipid(X2)and the concentration of D-mannose(X3) as factors. Using sodium lauryl sulfate as medium,in vitro release characteristics of cationic liposomes prepared with 1%octadecyl-amine was investigated by bag filter method,and compared with those of Asiaticoside solution and common liposome. RESULTS:The optimal formulation was X1 0.07,X2 0.17 and X3 0.03 g/ml. The encapsulation efficiency was (75.529 ± 1.071)%,and drug-loading amount was(2.539±0.029)%(n=3);the deviation from the predicted values were -0.217% and 0.205%;1% oc-tadecylamine was add into formulation to obtain cationic liposomes,and the Zeta potential had changed from -5.6 mV to 20.8 mV. in vitro accumulative release rates of Asiaticoside solution,common liposomes and cationic liposomes were 89.13%(12 h), 87.58%(72 h) and 94.46%(72 h),and the latter was in line with Weibull model. CONCLUSIONS:Asiaticoside cationic lipo-somes have high encapsulation efficiency,and can releases for 72 h.%目的:优化积雪草苷阳离子脂质体的处方,并对其体外释药特性进行考察。方法:采用薄膜分散法制备脂质体;以包封率、载药量为指标,以积雪草苷与磷脂质量比(药脂比,X1)、胆固醇与磷脂质量比(X2)、D-甘露糖质量浓度(X3)为因素,采用星点设计-响应面法优化处方;以十二烷基硫酸钠为介质,采用透析袋法考察加入1%十八胺所制阳离子脂质体的体外释药特性,并与积雪草苷的溶液及普通脂质体进行比较。结果:最优处方为X10.07、X20

  19. Evaluation of the protective effects of curcuminoid (curcumin and bisdemethoxycurcumin-loaded liposomes against bone turnover in a cell-based model of osteoarthritis

    Directory of Open Access Journals (Sweden)

    Yeh CC

    2015-04-01

    Full Text Available Chih-Chang Yeh,1,2 Yu-Han Su,3 Yu-Jhe Lin,3 Pin-Jyun Chen,3 Chung-Sheng Shi,1 Cheng-Nan Chen,3,* Hsin-I Chang3,* 1Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, Republic of China; 2Orthopaedic Department, Chiayi Branch, Taichung Veterans General Hospital, Chiayi, Taiwan, Republic of China; 3Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan, Republic of China *These authors contributed equally to this work Abstract: Curcumin (Cur and bisdemethoxycurcumin (BDMC, extracted from Curcuma longa, are poorly water-soluble polyphenol compounds that have shown anti-inflammatory potential for the treatment of osteoarthritis. To increase cellular uptake of Cur and BDMC in bone tissue, soybean phosphatidylcholines were used for liposome formulation. In this study, curcuminoid (Cur and BDMC-loaded liposomes were characterized in terms of particle size, encapsulation efficiency, liposome stability, and cellular uptake. The results show that there is about 70% entrapment efficiency of Cur and BDMC in liposomes and that particle sizes are stable after liposome formation. Both types of liposome can inhibit macrophage inflammation and osteoclast differential activities. In comparison with free drugs (Cur and BDMC, curcuminoid-loaded liposomes were less cytotoxic and expressed high cellular uptake of the drugs. Of note is that Cur-loaded liposomes can prevent liposome-dependent inhibition of osteoblast differentiation and mineralization, but BDMC-loaded liposomes could not. With interleukin (IL-1β stimulation, curcuminoid-loaded liposomes can successfully downregulate the expression of inflammatory markers on osteoblasts, and show a high osteoprotegerin (OPG/receptor activator of nuclear factor κB ligand (RANKL ratio to prevent osteoclastogenesis. In the present study, we demonstrated that Cur and BDMC can be successfully encapsulated in liposomes and

  20. Formulation and antifungal performance of natamycin-loaded liposomal suspensions: the benefits of sterol-enrichment.

    Science.gov (United States)

    Bouaoud, Clotilde; Lebouille, Jérôme G J L; Mendes, Eduardo; De Braal, Henriette E A; Meesters, Gabriel M H

    2016-06-01

    The aim of this study is to develop and evaluate food-grade liposomal delivery systems for the antifungal compound natamycin. Liposomes made of various soybean lecithins are prepared by solvent injection, leading to small unilamellar vesicles (Fine-tuning of sterol concentration allows preparation of liposomal suspensions presenting modulated in vitro release kinetics rates and enhanced antifungal activity against the model yeast Saccharomyces cerevisiae. PMID:26009272

  1. A novel approach for lung delivery of rifampicin-loaded liposomes in dry powder form for the treatment of tuberculosis

    OpenAIRE

    Jagadevappa S Patil; V Kusum Devi; Kshama Devi; Sarasija, S

    2015-01-01

    Background: Lung administration of antibiotics by nebulization is promising for improved treatment efficiency for pulmonary infections, as it increases drug concentration at sites of infection while minimizing systemic side effects. For poorly soluble molecules like rifampicin, lipid particulate system may improve lung delivery. Materials and Methods: We investigated rifampicin-loaded freeze-dried liposomes. Various formulations were prepared with different drug lipid ratios and one formulati...

  2. Liposomes Loaded with Hydrophobic Iron Oxide Nanoparticles: Suitable T2 Contrast Agents for MRI

    Science.gov (United States)

    Martínez-González, Raquel; Estelrich, Joan; Busquets, Maria Antònia

    2016-01-01

    There has been a recent surge of interest in the use of superparamagnetic iron oxide nanoparticles (SPIONs) as contrast agents (CAs) for magnetic resonance imaging (MRI), due to their tunable properties and their low toxicity compared with other CAs such as gadolinium. SPIONs exert a strong influence on spin-spin T2 relaxation times by decreasing the MR signal in the regions to which they are delivered, consequently yielding darker images or negative contrast. Given the potential of these nanoparticles to enhance detection of alterations in soft tissues, we studied the MRI response of hydrophobic or hydrophilic SPIONs loaded into liposomes (magnetoliposomes) of different lipid composition obtained by sonication. These hybrid nanostructures were characterized by measuring several parameters such as size and polydispersity, and number of SPIONs encapsulated or embedded into the lipid systems. We then studied the influence of acyl chain length as well as its unsaturation, charge, and presence of cholesterol in the lipid bilayer at high field strength (7 T) to mimic the conditions used in preclinical assays. Our results showed a high variability depending on the nature of the magnetic particles. Focusing on the hydrophobic SPIONs, the cholesterol-containing samples showed a slight reduction in r2, while unsaturation of the lipid acyl chain and inclusion of a negatively charged lipid into the bilayer appeared to yield a marked increase in negative contrast, thus rendering these magnetoliposomes suitable candidates as CAs, especially as a liver CA. PMID:27472319

  3. Theranostic liposomes loaded with quantum dots and apomorphine for brain targeting and bioimaging

    Directory of Open Access Journals (Sweden)

    Wen CJ

    2012-03-01

    Full Text Available Chih-Jen Wen1,*, Li-Wen Zhang2,*, Saleh A Al-Suwayeh3, Tzu-Chen Yen1, Jia-You Fang2,4 1Molecular Imaging Center, Chang Gung Memorial Hospital, Gueishan, Taoyuan, Taiwan; 2Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Gueishan, Taoyuan, Taiwan; 3Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 4Department of Cosmetic Science, Chang Gung University of Science and Technology, Gueishan, Taoyuan, Taiwan *These authors contributed equally to this workAbstract: Quantum dots (QDs and apomorphine were incorporated into liposomes to eliminate uptake by the liver and enhance brain targeting. We describe the preparation, physicochemical characterization, in vivo bioimaging, and brain endothelial cell uptake of the theranostic liposomes. QDs and the drug were mainly located in the bilayer membrane and inner core of the liposomes, respectively. Spherical vesicles with a mean diameter of ~140 nm were formed. QDs were completely encapsulated by the vesicles. Nearly 80% encapsulation percentage was achieved for apomorphine. A greater fluorescence intensity was observed in mouse brains treated with liposomes compared to free QDs. This result was further confirmed by ex vivo imaging of the organs. QD uptake by the heart and liver was reduced by liposomal incorporation. Apomorphine accumulation in the brain increased by 2.4-fold after this incorporation. According to a hyperspectral imaging analysis, multifunctional liposomes but not the aqueous solution carried QDs into the brain. Liposomes were observed to have been efficiently endocytosed into bEND3 cells. The mechanisms involved in the cellular uptake were clathrin- and caveola-mediated endocytosis, which were energy-dependent. To the best of our knowledge, our group is the first to develop liposomes with a QD-drug hybrid for the aim of imaging and treating brain disorders.Keywords: liposomes, quantum dots, apomorphine

  4. The anti-tumor effects of cordycepin-loaded liposomes on the growth of hepatoma 22 tumors in mice and human hepatoma BEL-7402 cells in culture.

    Science.gov (United States)

    Wu, Peng-Kai; Tao, Zhi; Ouyang, Zhao; Cao, Jiang-Ye; Geng, Di; Liu, Jin; Wang, Chun-Mei

    2016-09-01

    Liposomes have successfully been used for decades to encapsulate and protect drugs that are prone to deactivation in the body. The present study aimed to demonstrate the use of liposomes to encapsulate cordycepin, an adenosine analog that quickly loses its activity in vivo. The cordycepin-loaded liposomes were prepared by the ammonium sulfate gradient approach, and its in vitro and in vivo antitumour activities were evaluated using BEL-7402 cells and hepatocellular carcinoma H22 transplanted tumors, respectively. An MTT assay was used to observe the cytotoxicity of cells treated with cordycepin and cordycepin-loaded liposomes in vitro. High-content screening (HSC) was carried out using Hoechst 33342 to detect apoptotic cells and the ratio of cells in different cell cycle stages. The data demonstrated that both the cordycepin and the cordycepin-loaded liposomes resulted in clear cytotoxicity with IC50 values of 18.97 and 29.39 μg/mL, respectively. The latter showed significantly strong inhibitory effects on H22 tumor growth in mice, while the former did not show any inhibitory effects on tumor growth. In addition, the HSC assay showed that the cordycepin-loaded liposomes resulted in a higher rate of apoptosis than the cordycepin alone in BEL-7402 cells. Further data analysis revealed that the cells treated with cordycepin-loaded liposomes were predominately arrested at the G2/M phase (p < 0.05), while those treated with cordycepin alone were arrested in the G0/G1 phase (p < 0.05). In conclusion, these results suggest that liposomes can enhance and maintain the in vivo anti-tumor activity of cordycepin. PMID:26984179

  5. Glutamine-Loaded Liposomes: Preliminary Investigation, Characterization, and Evaluation of Neutrophil Viability.

    Science.gov (United States)

    Costa, Larissa Chaves; Souza, Bárbara Nayane Rosário Fernandes; Almeida, Fábio Fidélis; Lagranha, Cláudia Jacques; Cadena, Pabyton Gonçalves; Santos-Magalhães, Nereide Stela; Lira-Nogueira, Mariane Cajubá de Britto

    2016-04-01

    Glutamine has received attention due to its ability to ameliorate the immune system response. Once conventional liposomes are readily recognized and captured by immune system cells, the encapsulation of glutamine into those nanosystems could be an alternative to reduce glutamine dosage and target then to neutrophils. Our goals were to nanoencapsulate glutamine into conventional liposomes (Gln-L), develop an analytical high-performance liquid chromatography (HPLC) method for its quantification, and evaluate the viability of neutrophils treated with Gln-L. Liposomes were prepared using the thin-film hydration technique followed by sonication and characterized according to pH, mean size, zeta potential, and drug encapsulation efficiency (EE%). We also aimed to study the effect of liposomal constituent concentrations on liposomal characteristics. The viability of neutrophils was assessed using flow cytometry after intraperitoneal administration of free glutamine (Gln), Gln-L, unloaded-liposome (UL), and saline solution as control (C) in healthy Wistar rats. The selected liposomal formulation had a mean vesicle size of 114.65 ± 1.82 nm with a polydispersity index of 0.30 ± 0.00, a positive surface charge of 36.30 ± 1.38 mV, and an EE% of 39.49 ± 0.74%. The developed chromatographic method was efficient for the quantification of encapsulated glutamine, with a retention time at 3.8 min. A greater viability was observed in the group treated with glutamine encapsulated compared to the control group (17%), although neutrophils remain viable in all groups. Thus, glutamine encapsulated into liposomes was able to increase the number of viable neutrophils at low doses, thereby representing a promising strategy for the treatment of immunodeficiency conditions. PMID:26228746

  6. Transport of nanoparticles and tobramycin-loaded liposomes in Burkholderia cepacia complex biofilms.

    Directory of Open Access Journals (Sweden)

    Anne-Sophie Messiaen

    Full Text Available Due to the intrinsic resistance of Burkholderia cepacia complex (Bcc to many antibiotics and the production of a broad range of virulence factors, lung infections by these bacteria, primarily occurring in cystic fibrosis (CF patients, are very difficult to treat. In addition, the ability of Bcc organisms to form biofilms contributes to their persistence in the CF lung. As Bcc infections are associated with poor clinical outcome, there is an urgent need for new effective therapies to treat these infections. In the present study, we investigated whether liposomal tobramycin displayed an increased anti-biofilm effect against Bcc bacteria compared to free tobramycin. Single particle tracking (SPT was used to study the transport of positively and negatively charged nanospheres in Bcc biofilms as a model for the transport of liposomes. Negatively charged nanospheres became immobilized in close proximity of biofilm cell clusters, while positively charged nanospheres interacted with fiber-like structures, probably eDNA. Based on these data, encapsulation of tobramycin in negatively charged liposomes appeared promising for targeted drug delivery. However, the anti-biofilm effect of tobramycin encapsulated into neutral or anionic liposomes did not increase compared to that of free tobramycin. Probably, the fusion of the anionic liposomes with the negatively charged bacterial surface of Bcc bacteria was limited by electrostatic repulsive forces. The lack of a substantial anti-biofilm effect of tobramycin encapsulated in neutral liposomes could be further investigated by increasing the liposomal tobramycin concentration. However, this was hampered by the low encapsulation efficiency of tobramycin in these liposomes.

  7. First In Vivo Evaluation of Liposome-encapsulated 223Ra as a Potential Alpha-particle-emitting Cancer Therapeutic Agent

    Energy Technology Data Exchange (ETDEWEB)

    Jonasdottir, Thora J.; Fisher, Darrell R.; Borrebaek, Jorgen; Bruland, Oyvind S.; Larsen, Roy H.

    2006-09-13

    Liposomes carrying chemotherapeutics have had some success in cancer treatment and may be suitable carriers for therapeutic radionuclides. This study was designed to evaluate the biodistribution of and to estimate the radiation doses from the alpha emitter 223Ra loaded into pegylated liposomes in selected tissues. 223Ra was encapsulated in pegylated liposomal doxorubicin by ionophore-mediated loading. The biodistribution of liposomal 223Ra was compared to free cationic 223Ra in Balb/C mice. We showed that liposomal 223 Ra circulated in the blood with an initial half-time in excess of 24 hours, which agreed well with that reported for liposomal doxorubicin in rodents, while the blood half-time of cationic 223Ra was considerably less than one hour. When liposomal 223 Ra was catabolized, the released 223Ra was either excreted or taken up in the skeleton. This skeletal uptake increased up to 14 days after treatment, but did not reach the level seen with free 223Ra. Pre-treatment with non-radioactive liposomal doxorubicin 4 days in advance lessened the liver uptake of liposomal 223 Ra. Dose estimates showed that the spleen, followed by bone surfaces, received the highest absorbed doses. Liposomal 223 Ra was relatively stable in vivo and may have potential for radionuclide therapy and combination therapy with chemotherapeutic agents.

  8. Ocular and systemic bio-distribution of rhodamine-conjugated liposomes loaded with VIP injected into the vitreous of Lewis rats

    OpenAIRE

    Camelo, S.; Lajavardi, L.; Bochot, A.; Goldenberg, B.; Naud, M.C.; Fattal, E; Behar-Cohen, F; de Kozak, Y.

    2007-01-01

    Purpose Local delivery of therapeutic molecules encapsulated within liposomes is a promising method to treat ocular inflammation. The purpose of the present study was to define the biodistribution of rhodamine-conjugated liposomes loaded with vasoactive intestinal peptide (VIP), an immunosuppressive neuropeptide, following their intravitreal (IVT) injection in normal rats. Methods Healthy seven- to eight-week-old Lewis male rats were injected into the vitreous with empty rhodamine-conjugated ...

  9. Folate receptor-targeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for H22 hepatocellular carcinoma both in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Liu MC

    2016-04-01

    Full Text Available Min-Chen Liu,1 Lin Liu,1 Xia-Rong Wang,1 Wu-Ping Shuai,2 Ying Hu,3 Min Han,1 Jian-Qing Gao1 1Institute of Pharmaceutics, College of Pharmaceutical Sciences, 2First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 3Zhejiang Pharmaceutical College, Ningbo, People’s Republic of China Abstract: The diacid metabolite of norcantharidin (DM-NCTD is clinically effective against hepatocellular carcinoma (HCC, but is limited by its short half-life and high incidence of adverse effects at high doses. We developed a DM-NCTD-loaded, folic acid (FA-modified, polyethylene glycolated (DM-NCTD/FA-PEG liposome system to enhance the targeting effect and antitumor potency for HCC at a moderate dose based on our previous study. The DM-NCTD/FA-PEG liposome system produced liposomes with regular spherical morphology, with mean particle size approximately 200 nm, and an encapsulation efficiency >80%. MTT cytotoxicity assays demonstrated that the DM-NCTD/FA-PEG liposomes showed significantly stronger cytotoxicity effects on the H22 hepatoma cell line than did PEG liposomes without the FA modification (P<0.01. We used liquid chromatography–mass spectrometry for determination of DM-NCTD in tissues and tumors, and found it to be sensitive, rapid, and reliable. In addition, the biodistribution study showed that DM-NCTD liposomes improved tumor-targeting efficiency, and DM-NCTD/FA-PEG liposomes exhibited the highest efficiency of the treatments (P<0.01. Meanwhile, the results indicated that although the active liposome group had an apparently increased tumor-targeting efficiency of DM-NCTD, the risk to the kidney was higher than in the normal liposome group. With regard to in vivo antitumor activity, DM-NCTD/FA-PEG liposomes inhibited tumors in H22 tumor-bearing mice better than either free DM-NCTD or DM-NCTD/PEG liposomes (P<0.01, and induced considerably more significant cellular apoptosis in the tumors, with no obvious toxicity to the tissues

  10. An evaluation of the anti-tumor efficacy of oleanolic acid-loaded PEGylated liposomes

    International Nuclear Information System (INIS)

    The effective delivery of oleanolic acid (OA) to the target site has several benefits in therapy for different pathologies. However, the delivery of OA is challenging due to its poor aqueous solubility. The study aims to evaluate the tumor inhibition effect of the PEGylated OA nanoliposome on the U14 cervical carcinoma cell line. In our previous study, OA was successfully encapsulated into PEGylated liposome with the modified ethanol injection method. Oral administration of PEGylated OA liposome was demonstrated to be more efficient in inhibiting xenograft tumors. The results of organ index indicated that PEG liposome exhibited higher anti-tumor activity and lower cytotoxicity. It was also found that OA and OA liposomes induced tumor cell apoptosis detected by flow cytometry. Furthermore, effects of OA on the morphology of tumor and other tissues were observed by hematoxylin and eosin staining. The histopathology sections did not show pathological changes in kidney or liver in tested mice. In contrast, there was a significant difference in tumor tissues between treatment groups and the negative control group. These observations imply that PEGylated liposomes seem to have advantages for cancer therapy in terms of effective delivery of OA. (paper)

  11. Cytotoxicity of 5-fluorouracil-loaded pH-sensitive liposomal nanoparticles in colorectal cancer cell lines

    OpenAIRE

    Udofot, Ofonime; Affram, Kevin; Israel, Bridg'ette; Agyare, Edward

    2015-01-01

    5-Fluorouracil (5-FU) is widely used in cancer therapy, either alone or in combination with other anti-cancer drugs. However, poor membrane permeability and a short half-life (5-20 min) due to rapid metabolism in the body necessitate the continuous administration of high doses of 5-FU to maintain the minimum therapeutic serum concentration. This is associated with significant side effects and a possibility of severe toxic effects. This study aimed to formulate 5-FU-loaded pH-sensitive liposom...

  12. pH-Sensitive carboxymethyl chitosan-modified cationic liposomes for sorafenib and siRNA co-delivery

    OpenAIRE

    Yao Y; Su ZH; Liang YC; Zhang N.

    2015-01-01

    Yao Yao, Zhihui Su, Yanchao Liang, Na Zhang School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, People’s Republic of China Abstract: Combination of chemotherapeutic drug and small interfering RNA (siRNA) can affect multiple disease pathways and has been proven effective in suppressing tumor progression. Co-delivery of drug and siRNA within a same nanocarrier is a vital means in this field. The present study aimed at the development of a pH-sensitive liposome t...

  13. Inhibition of B16BL6 tumor progression by coadministration of recombinant angiostatin K1-3 and endostatin genes with cationic liposomes.

    Science.gov (United States)

    Kim, Keun Sik; Kim, Hong Sung; Park, Jin Seu; Kwon, Young Guen; Park, Yong Serk

    2004-06-01

    Transfection of the antiangiogenic angiostatin and endostatin genes was shown to be an alternative to high-dose administration of angiostatin or endostatin proteins for cancer therapy. We have systematically investigated whether coadministration of the mouse angiostatin kringle 1-3 gene (pFLAG-AngioK1/3) and the endostatin gene (pFLAG-Endo) complexed with cationic liposomes exhibits enhanced therapeutic efficacy. In vitro, the coexpressed mixture of angiostatin K1-3 and endostatin more effectively reduced angiogenesis in chorioallantoic membranes than either angiostatin K1-3 or endostatin alone. In vivo, subcutaneous co-administration of pFLAG-AngioK1/3 and pFLAG-Endo lipoplexes more effectively inhibited vascularization in Matrigel plugs implanted in mice than either one alone. Additionally, subcutaneous administration of these genes inhibited the growth and formation of pulmonary metastases of B16BL6 melanoma cells in mice. Compared to treatment with an empty vector, treatment with pFLAG-AngioK1/3 plus pFLAG-Endo inhibited 81% of tumor growth, while treatment with pFLAG-AngioK1/3 or pFLAG-Endo inhibited tumor growth 70 and 69%, respectively. Cotreatment with the two plasmids after primary tumor excision induced a 90% inhibition of pulmonary metastases versus 79% for pFLAG-AngioK1/3 or 80% for pFLAG-Endo individually. These results suggest that combined administration of angiostatin K1-3 and endostatin genes complexed with cationic liposomes may be an innovated antiangiogenic strategy for cancer therapy. PMID:15118757

  14. Baicalin loaded in folate-PEG modified liposomes for enhanced stability and tumor targeting

    Czech Academy of Sciences Publication Activity Database

    Chen, Y.; Minh, L. V.; Liu, J.; Angelov, Borislav; Drechsler, M.; Garamus, V. M.; Willumeit-Römer, R.; Zou, A.

    2016-01-01

    Roč. 140, 1 April (2016), s. 74-82. ISSN 0927-7765 R&D Projects: GA ČR(CZ) GC15-10527J Institutional support: RVO:61389013 Keywords : baicalin * liposomes * folate receptor Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 4.152, year: 2014

  15. Cytotoxic effects of Gemcitabine-loaded liposomes in human anaplastic thyroid carcinoma cells

    Directory of Open Access Journals (Sweden)

    Rotiroti Domenicoantonio

    2004-09-01

    Full Text Available Abstract Background Identification of effective systemic antineoplastic drugs against anaplastic thyroid carcinomas has particularly important implications. In fact, the efficacy of the chemotherapeutic agents presently used in these tumours, is strongly limited by their low therapeutic index. Methods In this study gemcitabine was entrapped within a pegylated liposomal delivery system to improve the drug antitumoral activity, thus exploiting the possibility to reduce doses to be administered in cancer therapy. The cytotoxic effects of free or liposome-entrapped gemcitabine was evaluated against a human thyroid tumour cell line. ARO cells, derived from a thyroid anaplastic carcinoma, were exposed to different concentrations of the drug. Liposomes formulations were made up of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-MPEG (8:3:1 molar ratio. Cell viability was assessed by both trypan bleu dye exclusion assay and fluorimetric analysis of cell DNA content. Results A cytotoxic effect of free gemcitabine was present only after 72 h incubation (ARO cell mortality increased of approximately 4 fold over control at 1 μM, 7 fold at 100 μM. When gemcitabine was encapsulated in liposomes, a significant effect was observed by using lower concentrations of the drug (increased cell mortality of 2.4 fold vs. control at 0.3 μM and earlier exposure time (24 h. Conclusion These findings show that, in vitro against human thyroid cancer cells, the gemcitabine incorporation within liposomes enhances the drug cytotoxic effect with respect to free gemcitabine, thus suggesting a more effective drug uptake inside the cells. This may allow the use of new formulations with lower dosages (side effect free for the treatment of anaplastic human thyroid tumours.

  16. Cytotoxic effects of Gemcitabine-loaded liposomes in human anaplastic thyroid carcinoma cells

    International Nuclear Information System (INIS)

    Identification of effective systemic antineoplastic drugs against anaplastic thyroid carcinomas has particularly important implications. In fact, the efficacy of the chemotherapeutic agents presently used in these tumours, is strongly limited by their low therapeutic index. In this study gemcitabine was entrapped within a pegylated liposomal delivery system to improve the drug antitumoral activity, thus exploiting the possibility to reduce doses to be administered in cancer therapy. The cytotoxic effects of free or liposome-entrapped gemcitabine was evaluated against a human thyroid tumour cell line. ARO cells, derived from a thyroid anaplastic carcinoma, were exposed to different concentrations of the drug. Liposomes formulations were made up of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol/ 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-MPEG (8:3:1 molar ratio). Cell viability was assessed by both trypan bleu dye exclusion assay and fluorimetric analysis of cell DNA content. A cytotoxic effect of free gemcitabine was present only after 72 h incubation (ARO cell mortality increased of approximately 4 fold over control at 1 μM, 7 fold at 100 μM). When gemcitabine was encapsulated in liposomes, a significant effect was observed by using lower concentrations of the drug (increased cell mortality of 2.4 fold vs. control at 0.3 μM) and earlier exposure time (24 h). These findings show that, in vitro against human thyroid cancer cells, the gemcitabine incorporation within liposomes enhances the drug cytotoxic effect with respect to free gemcitabine, thus suggesting a more effective drug uptake inside the cells. This may allow the use of new formulations with lower dosages (side effect free) for the treatment of anaplastic human thyroid tumours

  17. Small Angle X-ray and Neutron Scattering: Powerful Tools for Studying the Structure of Drug-Loaded Liposomes

    Science.gov (United States)

    Di Cola, Emanuela; Grillo, Isabelle; Ristori, Sandra

    2016-01-01

    Nanovectors, such as liposomes, micelles and lipid nanoparticles, are recognized as efficient platforms for delivering therapeutic agents, especially those with low solubility in water. Besides being safe and non-toxic, drug carriers with improved performance should meet the requirements of (i) appropriate size and shape and (ii) cargo upload/release with unmodified properties. Structural issues are of primary importance to control the mechanism of action of loaded vectors. Overall properties, such as mean diameter and surface charge, can be obtained using bench instruments (Dynamic Light Scattering and Zeta potential). However, techniques with higher space and time resolution are needed for in-depth structural characterization. Small-angle X-ray (SAXS) and neutron (SANS) scattering techniques provide information at the nanoscale and have therefore been largely used to investigate nanovectors loaded with drugs or other biologically relevant molecules. Here we revise recent applications of these complementary scattering techniques in the field of drug delivery in pharmaceutics and medicine with a focus to liposomal carriers. In particular, we highlight those aspects that can be more commonly accessed by the interested users. PMID:27043614

  18. Preparation of liposomes loaded with quantum dots, fluorescence resonance energy transfer studies, and near-infrared in-vivo imaging of mouse tissue

    International Nuclear Information System (INIS)

    We report on a simple, fast and convenient method to engineer lipid vesicles loaded with quantum dots (QDs) by incorporating QDs into a vesicle-type of lipid bilayer using a phase transfer reagent. Hydrophilic CdTe QDs and near-infrared (NIR) QDs of type CdHgTe were incorporated into liposomes by transferring the QDs from an aqueous solution into chloroform by addition of a surfactant. The QD-loaded liposomes display bright fluorescence, and the incorporation of the QDs into the lipid bilayer leads to enhanced storage stability and reduced sensitivity to UV irradiation. The liposomes containing the QD were applied to label living cells and to image mouse tissue in-vivo using a confocal laser scanning microscope, while NIR images of mouse tissue were acquired with an NIR fluorescence imaging system. We also report on the fluorescence resonance energy transfer (FRET) that occurs between the CdTe QDs (the donor) and the CdHgTe QDs (the acceptor), both contained in liposomes. Based on these data, this NIR FRET system shows promise as a tool that may be used to study the release of drug-loaded liposomes and their in vivo distribution. (author)

  19. A comparative evaluation of coenzyme Q10-loaded liposomes and solid lipid nanoparticles as dermal antioxidant carriers

    Directory of Open Access Journals (Sweden)

    Gokce EH

    2012-09-01

    Full Text Available Evren H Gokce,1 Emrah Korkmaz,1 Sakine Tuncay-Tanriverdi,1 Eleonora Dellera,2 Giuseppina Sandri,2 M Cristina Bonferoni,2 Ozgen Ozer11Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ege, Izmir, Turkey; 2Department of Drug Sciences, University of Pavia, Pavia, ItalyBackground: The effective delivery of coenzyme Q10 (Q10 to the skin has several benefits in therapy for different skin pathologies. However, the delivery of Q10 to deeper layers of skin is challenging due to low aqueous solubility of Q10. Liposomes and solid lipid nanoparticles (SLN have many advantages to accomplish the requirements in topical drug delivery. This study aims to evaluate the influence of these nanosystems on the effective delivery of Q10 into the skin.Methods: Q10-loaded liposomes (LIPO-Q10 and SLNs (SLN-Q10 were prepared by thin film hydration and high shear homogenization methods, respectively. Particle size (PS, polydispersity index (PI, zeta potential (ZP, and drug entrapment efficiency were determined. Differential scanning calorimetry analysis and morphological transmission electron microscopy (TEM examination were conducted. Biocompatibility/cytotoxicity studies of Q10-loaded nanosystems were performed by means of cell culture (human fibroblasts under oxidative conditions. The protective effect of formulations against production of reactive oxygen species were comparatively evaluated by cytofluorometry studies.Results: PS of uniform SLN-Q10 and LIPO-Q10 were determined as 152.4 ± 7.9 nm and 301.1 ± 8.2 nm, respectively. ZPs were −13.67 ± 1.32 mV and −36.6 ± 0.85 mV in the same order. The drug entrapment efficiency was 15% higher in SLN systems. TEM studies confirmed the colloidal size. SLN-Q10 and LIPO-Q10 showed biocompatibility towards fibroblasts up to 50 µM of Q10, which was determined as suitable for cell proliferation. The mean fluorescence intensity % depending on ROS production determined in cytofluorometric studies

  20. LyP-1-conjugated doxorubicin-loaded liposomes suppress lymphatic metastasis by inhibiting lymph node metastases and destroying tumor lymphatics

    Energy Technology Data Exchange (ETDEWEB)

    Yan Zhiqiang; Zhan Changyou; Wen Ziyi; Feng Linglin; Wang Fei; Liu Yu; Yang Xiangkun; Dong Qing; Liu Min; Lu Weiyue, E-mail: wylu@shmu.edu.cn [Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203 (China)

    2011-10-14

    Lymphatic metastasis can be greatly promoted by metastases growth and lymphangiogenesis in lymph nodes (LNs). LyP-1, a cyclic peptide, is able to specifically bind with tumor cells and tumor lymphatics in metastatic LNs. This work aimed to use LyP-1-conjugated liposomes (L-LS) loaded with doxorubicin (DOX) (L-LS/DOX) to suppress lymphatic metastasis by inhibiting both metastases and tumor lymphatics in LNs. L-LS were prepared and exhibited sizes around 90 nm and spherical morphology as characterized by transmission electron microscopy. The in vitro cellular studies showed that LyP-1 modification obviously increased liposome uptake by MDA-MB-435 tumor cells and enhanced the cytotoxicity of liposomal DOX. A popliteal and iliac LN metastases model was successfully established by subcutaneous inoculation of tumor cells to nude mice. The immunofluorescence staining analysis indicated that LyP-1 modification enabled specific binding of liposome with tumor lymphatics and enhanced the destroying effect of liposomal DOX on tumor lymphatics. The in vivo fluorescence imaging and pharmacodynamic studies showed that LyP-1 modification increased liposome uptake by metastatic LNs and that L-LS/DOX significantly decreased metastatic LN growth and LN metastasis rate. These results suggested that L-LS/DOX were an effective delivery system for suppressing lymphatic metastasis by simultaneously inhibiting LN metastases and tumor lymphatics.

  1. Nitric Oxide Loaded Echogenic Liposomes for Nitric Oxide Delivery and Inhibition of Intimal Hyperplasia

    Science.gov (United States)

    Huang, Shao-Ling; Kee, Patrick H.; Kim, Hyunggun; Moody, Melanie R.; Chrzanowski, Stephen M.; MacDonald, Robert C.; McPherson, David D.

    2011-01-01

    Objective To develop a new bioactive gas delivery method using echogenic liposomes (ELIP) as the gas carrier. Background Nitric oxide (NO) is a bioactive gas with potent therapeutic effects. Bioavailability of NO by systemic delivery is low with potential systemic effects. Methods Liposomes containing phospholipids and cholesterol were prepared using a new freezing under pressure method. The encapsulation and release profile of NO from NO containing-ELIP (NO-ELIP) or a mixture of NO/Argon (NO/Ar-ELIP was studied. Uptake of NO from NO-ELIP by cultured vascular smooth muscle cells (VSMC) both in the absence and presence of hemoglobin was determined. The effect of NO-ELIP delivery to attenuate intimal hyperplasia in a balloon-injured artery was determined. Results Coencapsulation of NO with argon (Ar) enabled the adjustment the amount of encapsulated NO. A total of 10 µl of gas can be encapsulated into 1 mg liposomes. The release profile of NO from NO-ELIP demonstrated an initial rapid release followed by a slower release over 8 hours. Sixty-eight percent of cells remained viable when incubated with 80 µg/ml of NO/Ar-ELIP for 4 hours. NO delivery to VSMC using NO/Ar-ELIP was 7-fold higher than unencapsulated NO. NO/Ar-ELIP remained effective NO delivery to VSMC even in the presence of hemoglobin. Local NO-ELIP administration to balloon-injured carotid arteries attenuated the development of intimal hyperplasia and reduced arterial wall thickening by 41±9%. Conclusions Liposomes can protect and deliver a bioactive gas to target tissues with the potential for both visualization of gas delivery and controlled therapeutic gas release. PMID:19660697

  2. Mechanistic study of decreased skin penetration using a combination of sonophoresis with sodium fluorescein-loaded PEGylated liposomes with D-limonene

    Directory of Open Access Journals (Sweden)

    Rangsimawong W

    2015-12-01

    Full Text Available Worranan Rangsimawong, Praneet Opanasopit, Theerasak Rojanarata, Tanasait Ngawhirunpat Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand Abstract: The effect of low frequency sonophoresis (SN, 20 kHz on the skin transport of sodium fluorescein (NaFI-loaded liposomes was investigated. An in vitro skin penetration study in open and blocked hair follicles was performed, and confocal laser scanning microscopy and scanning electron microscopy were used to visualize the penetration pathways. The results showed that SN significantly increased the flux of NaFI solution, whereas it significantly decreased the flux of NaFI-loaded polyethylene glycol-coated (PEGylated liposomes with D-limonene (PL-LI. SN did not significantly affect the flux of NaFI-loaded conventional liposomes and PEGylated liposomes. In the blocked follicles, the flux of NaFI-loaded PL-LI both with and without SN decreased, indicating that NaFI-loaded PL-LI penetrated the skin via the transfollicular pathway. A confocal laser scanning microscopy image showed that in the skin without SN, the fluorescence intensity of NaFI-loaded PL-LI was observed in the skin and along the length of hair inside the skin, whereas in the skin with applied SN, the fluorescence intensity was detected only on the top of hair outside the skin. From scanning electron microscopy images, SN dislocated the corneocytes and reduced the deposition of PL-LI around hair follicles. These results revealed that SN may partially plug hair follicle orifices and reduce percutaneous absorption through the follicular pathway. Keywords: sonophoresis, PEGylated liposomes, hydrophilic compound, follicular pathway

  3. Construction of a novel cationic polymeric liposomes formed from PEGlated octadecyl-quaternized lysine modified chitosan/cholesterol for enhancing storage stability and cellular uptake efficiency.

    Science.gov (United States)

    Wang, Hanjie; Zhao, Peiqi; Liang, Xiaofei; Song, Tao; Gong, Xiaoqun; Niu, Ruifang; Chang, Jin

    2010-08-15

    The design and construction of delivery vectors with high stability and effective cellular uptake efficiency is very important. In this study, a novel polymeric liposomes (PLs) formed from PEGlated octadecyl-quaternized lysine modified chitosan (OQLCS) and cholesterol with higher size stability and cellular uptake efficiency has been synthesized successfully. Compared to conventional liposomes (CLs; phosphatidyl choline/cholesterol), the calcein-loaded PLs exhibited a multi-lamellar structure with homogenous size diameter (200 nm) and high calcein encapsulation efficiency (about 92%). PLs could be stored at different temperature (25, 4, and -20 degrees C) and different medium (deionized water, phosphate-buffered saline, and human plasma solution) for up to 4 weeks without significant size change. The spectrophotometer fluorometry analysis and the flow cytometry analysis indicated that in comparison with CL, PLs with positive zeta potential facilitates the uptake of calcein by MCF-7 tumor cells. The data suggests that PLs may provide a new method to overcome the stability and enhance the uptake efficiency of CLs. PMID:20506161

  4. Remote Loading of 64Cu2+ into Liposomes without the Use of Ion Transport Enhancers

    DEFF Research Database (Denmark)

    Henriksen, Jonas Rosager; Petersen, Anncatrine Luisa; Hansen, Anders Elias;

    2015-01-01

    Due to low ion permeability of lipid bilayers, it has been and still is common practice to use transporter molecules such as ionophores or lipophilic chelators to increase transmembrane diffusion rates and loading efficiencies of radionuclides into liposomes. Here, we report a novel and very simple...

  5. Optimization of a cationic liposome-based gene delivery system for the application of miR-145 in anticancer therapeutics.

    Science.gov (United States)

    Tao, Jin; Ding, Wei-Feng; Che, Xiao-Hang; Chen, Yi-Chen; Chen, Fang; Chen, Xiao-Dong; Ye, Xiao-Lei; Xiong, Su-Bin

    2016-05-01

    In order to improve the delivery efficiency of microRNA (miRNA or miR)-145, the present study examined several factors which may affect cationic liposome (CL)-based transfection, including the hydration medium used for the preparation of liposomes, the quantity of the plasmid, the molar ratio of N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTAP)/cholesterol (chol), or DOTAP/chol, and the weight ratio of DOTAP/DNA. In order to enhance the transfection efficiency, protamine was selected as a DNA-condensing agent to form liposome‑protamine‑DNA (LPD) ternary complexes. An agarose gel retardation assay was used to examine the DNA binding affinity of the CLs. Following transfection, GFP fluorescence images were captured and flow cytometry was performed to determine the transfection efficiency. Furthermore, an MTT assay was performed to determine the cytotoxicity of the liposome complexes. The final optimal conditions were as follows: 5% glucose as the hydration medium, a molar ratio of DOTAP/chol at 3:1 for the preparation of CLs, a weight ratio of DOTAP/protamine/DNA of 3:0.5:1, with 8 µg plasmid added for the preparation of the LPD complexes. In vitro, the LPD complexes exhibited an enhanced transfection efficiency and low cytotoxicity, which indicated that the presented LPD vector enhanced the transfection efficiency of the CLs. The HepG2 cells were found to have the lowest expression levels of miR‑145 out of the cell lines tested (A549, BGC-823, HepG2, HeLa, LoVo and MCF-7). Following the transient transfection of the HepG2 cells with miR‑145, the results revealed that the overexpression of miR‑145 inhibited the proliferation of the HepG2 cells and downregulated the expression of cyclin-dependent kinase 6 (CDK6), cyclinD1, c-myc, and Sp1 transcription factor (Sp1). In conclusion, in this study, we optimized a liposome‑based delivery system for the efficient delivery of miR‑145 into cancer cells. This may provide a foundation for

  6. Tretinoin-loaded liposomal formulations: from lab to comparative clinical study in acne patients.

    Science.gov (United States)

    Rahman, Salwa Abdel; Abdelmalak, Nevine Shawky; Badawi, Alia; Elbayoumy, Tahany; Sabry, Nermeen; El Ramly, Amany

    2016-05-01

    Topical tretinoin is the most commonly used retinoid for acne. However, its irritative potential on the applied area and the barrier properties of the stratum corneum limit its use. The objective of the present study was to formulate tretinoin liposomal gel to obtain a formula with lower skin irritation potential and greater clinical effect. A statistical 2(4) factorial design was adopted. Sixteen formulae prepared and were properly evaluated. A candidate formula (F13G) prepared with 0.025% tretinoin, phospholipid- cholesterol-dicetylphosphate (9:1:0.01) and incorporated in 1% carbopol gel was selected for skin irritation test. Clinical study was conducted on acne patients and compared to marketed product. All liposomes formulations were spherical in shape. The addition of cholesterol in the film hydration method significantly decreased the vesicle size, and increased the percentage of incorporation efficiency at (p acne patients revealed that F13G showed significantly higher efficacy when compared to marketed product (p < 0.05). PMID:26004128

  7. Antiviral effect of HPMPC (Cidofovir (R)), entrapped in cationic liposomes: In vitro study on MDBK cell and BHV-1 virus

    Czech Academy of Sciences Publication Activity Database

    Korvasová, Z.; Drašar, L.; Mašek, J.; Turánek Knotigová, P.; Kulich, P.; Matiašovic, J.; Kovařčík, K.; Bartheldyová, E.; Koudelka, Š.; Škrabalová, M.; Miller, A. D.; Holý, Antonín; Ledvina, Miroslav; Turánek, J.

    2012-01-01

    Roč. 160, č. 2 (2012), s. 330-338. ISSN 0168-3659 R&D Projects: GA ČR(CZ) GAP304/10/1951; GA AV ČR(CZ) KAN200520703; GA AV ČR KAN200100801 Institutional research plan: CEZ:AV0Z40550506 Keywords : cationic lipids * BHV-1 virus * Cidofovir * HPMC * antiviral drugs Subject RIV: CC - Organic Chemistry Impact factor: 7.633, year: 2012

  8. Development of gatifloxacin-loaded cationic polymeric nanoparticles for ocular drug delivery.

    Science.gov (United States)

    Duxfield, Linda; Sultana, Rubab; Wang, Ruokai; Englebretsen, Vanessa; Deo, Samantha; Swift, Simon; Rupenthal, Ilva; Al-Kassas, Raida

    2016-03-01

    The present investigation aimed at improving the ocular bioavailability of gatifloxacin by prolonging its residence time in the eye and reducing problems associated with the drug re-crystallization after application through incorporation into cationic polymeric nanoparticles. Gatifloxacin-loaded nanoparticles were prepared via the nanoprecipitation and double emulsion techniques. A 50:50 Eudragit® RL and RS mixture was used as cationic polymer with other formulation parameters varied. Prepared nanoparticles were evaluated for size, zeta potential, and drug loading. An optimized formulation was selected and further characterized for in vitro drug release, cytotoxicity, and antimicrobial activity. The double emulsion method produced larger nanoparticles than the nanoprecipitation method (410 nm and 68 nm, respectively). Surfactant choice also affected particle size and zeta potential with Tween 80 producing smaller-sized particles with higher zeta potential than PVA. However, the zeta potential was positive at all experimental conditions investigated. The optimal formulation produced by double emulsion technique and has achieved 46% drug loading. This formulation had optimal physicochemical properties with acceptable cytotoxicity results, and very prolonged release rate. The particles antimicrobial activities of the selected formulation have been tested against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus and showed prolonged antimicrobial effect for gatifloxacin. PMID:26794936

  9. A gold nanoshell with a silica inner shell synthesized using liposome templates for doxorubicin loading and near-infrared photothermal therapy

    Directory of Open Access Journals (Sweden)

    Wu CY

    2011-04-01

    Full Text Available Congyu Wu1, Cong Yu1, Maoquan Chu1,21School of Life Science and Technology, 2The Institute for Advanced Materials and Nano Biomedicine, Tongji University, Shanghai, People's Republic of ChinaAbstract: Gold (Au nanoshells with solid silica cores have great potential for cancer photothermal therapy. However, this nanostructure cannot carry enough drugs. Here, we report a Au nanoshell with a hollow silica core for drug loading and cancer therapy. The silica shells were synthesized using nanoliposome templates, and then Au nanoshells were grown on the outer surface of the silica shells. Transmission-electron and scanning-electron microscopy showed that the Au nanoshells were successfully fabricated, and that the liposome/SiO2/Au core-shell nanocomposites were spherical with a narrow size distribution. Images of several broken spheres, and the fact that hollow templates (liposomes were used, suggest that the fabricated Au nanoshells were hollow. After doxorubicin (DOX was incorporated into liposome/SiO2/Au, the DOX-loaded Au nanoshells killed cancer cells with high therapeutic efficacy when irradiated with near-infrared light, suggesting that the Au nanoshells delivered both DOX chemotherapy and photothermal therapy with a synergistic effect.Keywords: gold nanoshell, liposome template, synthesis, doxorubicin, cancer therapy

  10. Penetration of tamoxifen citrate loaded ethosomes and liposomes across human skin: a comparative study with confocal laser scanning microscopy.

    Science.gov (United States)

    Sarwa, Khomendra K; Suresh, Preeti K; Rudrapal, Mithun; Verma, Vinod K

    2014-01-01

    In the present study, ethosomal and liposomal formulations containing tamoxifen citrate were prepared and evaluated for their penetration properties in human cadaver skin using Franz diffusion cell and confocal laser scanning microscope (CLSM). The results clearly revealed that ethosomal vesicles showed a better drug permeation profile than that of liposomal vesicles. In addition, low fluorescence intensity in CLSM was recorded with liposomes as compared to ethosomes, indicating lower cumulative amount of drug permeation from liposomal vesicles. Furthermore, CLSM showed uniform fluorescence intensity across the entire depth of skin in ethosomal treatment, indicating high penetrability of ethosomal vesicles through human cadaver skin. In contrast, low penetrability of conventional liposomal vesicles was recorded as penetration was limited to the 7(th) section (i.e. upper epidermis layer) of skin as evident from visualization of intact liposomal vesicles in CLSM. PMID:24428443

  11. Electrostatically driven complexation of liposomes with a star-shaped polyelectrolyte to low-toxicity multi-liposomal assemblies.

    Science.gov (United States)

    Yaroslavov, Alexander A; Sybachin, Andrey V; Zaborova, Olga V; Pergushov, Dmitry V; Zezin, Alexander B; Melik-Nubarov, Nikolay S; Plamper, Felix A; Müller, Axel H E; Menger, Frederic M

    2014-04-01

    Anionic liposomes are electrostatically complexed to a star-shaped cationic polyelectrolyte. Upon complexation, the liposomes retain their integrity and the resulting liposome-star complexes do not dissociate in a physiological solution with 0.15 M NaCl. This provides a multi-liposomal container for possible use as a high-capacity carrier. PMID:24243764

  12. Transferrin-loaded nido-carborane liposomes. Synthesis and intracellular targeting to solid tumors for boron neutron capture therapy

    International Nuclear Information System (INIS)

    The boron ion cluster lipids, as a double-tailed boron lipid synthesized from heptadecanol, formed stable liposomes at 25% molar ratio toward DSPC with cholesterol. Transferrin was able to be introduced on the surface of boron liposomes (Tf-PEG-CL liposomes) by the coupling of transferrin to the PEG-CO2H moieties of PEG-CL liposomes. The biodistribution of Tf-PEG-CL liposomes showed that Tf-PEG-CL liposomes accumulated in tumor tissues and stayed there for a sufficiently long time to increase tumor:blood concentration ratio. A 10B concentration of 22 ppm in tumor tissues was achieved by the injection of Tf-PEG-CL liposome at 7.2 mg/kg body weight 10B in tumor-bearing mice. After neutron irradiation, the average survival rate of mice not treated with Tf-PEG-CL liposomes was 21 days, whereas that of the treated mice was 31 days. Longer survival rates were observed in the mice treated with Tf-PEG-CL liposomes; one of them even survived for 52 days after BNCT. (author)

  13. Multi-liposomal containers.

    Science.gov (United States)

    Yaroslavov, A A; Sybachin, A V; Zaborova, O V; Zezin, A B; Talmon, Y; Ballauff, M; Menger, F M

    2015-12-01

    Small unilamellar liposomes, 40-60 nm in diameter, composed of anionic diphosphatidylglycerol (cardiolipin, CL(2-)) or phosphatidylcerine (PS(1-)) and zwitter-ionic egg yolk lecithin (EL) or dipalmitoylphosphatidylcholine (DPPC), electrostatically complex with polystyrene microspheres, ca. 100 nm in diameter, grafted by polycationic chains ("spherical polycationic brushes", SPBs). Polymer/liposome binding studies were carried out using electrophoretic mobility (EPM), dynamic light scattering (DLS), fluorescence, conductometry, differential scanning calorimetry (DSC), and cryogenic transmission electron microscopy (cryo-TEM) as the main analytical tools. By these means a remarkably detailed picture emerges of molecular events inside a membrane. The following are among the most important conclusions that arose from the experiments: (a) binding of liposomes to SPBs is accompanied by flip-flop of anionic lipids from the inner to the outer leaflet of the liposomal membrane along with lateral lipid segregation into "islands". (b) The SPB-induced structural reorganization of the liposomal membrane, together with the geometry of anionic lipid molecules, determines the maximum molar fraction of anionic lipid (a key parameter designated as ν) that ensures the structural integrity of liposomes upon complexation: ν=0.3 for liposomes with conically-shaped CL(2-) and ν=0.5 for liposomes with anionic cylindrically-shaped PS(1-). (c) The number of intact liposomes per SPB particle varies from 40 for (ν=0.1) to 13 (ν=0.5). (d) By using a mixture of liposomes with variety of encapsulated substances, multi-liposomal complexes can be prepared with a high loading capacity and a controlled ratio of the contents. (e) In order to make the mixed anionic liposomes pH-sensitive, they are additionally modified by 30 mol% of a morpholinocyclohexanol-based lipid that undergoes a conformational flip when changing pH. Being complexed with SPBs, such liposomes rapidly release their contents

  14. Thrombolytic efficacy and enzymatic activity of rt-PA-loaded echogenic liposomes.

    Science.gov (United States)

    Bader, Kenneth B; Bouchoux, Guillaume; Peng, Tao; Klegerman, Melvin E; McPherson, David D; Holland, Christy K

    2015-08-01

    Echogenic liposomes (ELIP), that can encapsulate both recombinant tissue-type plasminogen activator (rt-PA) and microbubbles, are under development to improve the treatment of thrombo-occlusive disease. However, the enzymatic activity, thrombolytic efficacy, and stable cavitation activity generated by this agent has yet to be evaluated and compared to another established ultrasound-enhanced thrombolytic scheme. A spectrophotometric method was used to compare the enzymatic activity of the rt-PA incorporated into ELIP (t-ELIP) to that of rt-PA. An in vitro flow model was employed to measure the thrombolytic efficacy and dose of ultraharmonic emissions from stable cavitation for 120-kHz ultrasound exposure of three treatment schemes: rt-PA, rt-PA and the perfluorocarbon-filled microbubble Definity(®), and t-ELIP. The enzymatic activity of rt-PA incorporated into t-ELIP was 28 % that of rt-PA. Thrombolytic efficacy of t-ELIP or rt-PA and Definity(®) was equivalent when the dose of t-ELIP was adjusted to produce comparable enzymatic activity. Sustained bubble activity was nucleated from Definity but not from t-ELIP exposed to 120-kHz ultrasound. These results emphasize the advantages of encapsulating a thrombolytic and the importance of incorporating an insoluble gas required to promote sustained, stable cavitation activity. PMID:25829338

  15. Novel 1,3-diacylamidopropane-2-[bis-(2-dimethylaminoethane)] carbamate pH-sensitive lipids for cationic liposome-mediated transfection

    Science.gov (United States)

    Spelios, Michael G.

    A novel series of 1,3-diacylamidopropane-2-[bis(2-dimethylaminoethane)] carbamate analogs (1,3lb) were designed for cationic lipid-assisted transfection (lipofection). First, their physicochemical properties in self-assemblies with and without plasmid DNA (pDNA) were evaluated to examine the effects of hydrophobic tail length and degree of saturation on gene delivery and expression. Significant in vitro lipofection was induced at a nitrogen:phosphate ratio (N:P) of 4:1 by the dimyristoyl, dipalmitoyl, and dioleoyl analogs 1,3lb2, 1,3lb3, and 1,3lb5, respectively, without inclusion of neutral "lipofection enhancing" co-lipids in the cationic lipid formulations. Lipofection was reduced in the presence of co-lipids except for 1,3lb5 which maintained reporter gene expression levels at N:P 4:1 and yielded increased bioactivity at a lower NP of 2:1. Physicochemical characterization of the bioactive transfection agents (cytofectins) revealed: high hydration and in-plane elasticity of lipid monolayers by Langmuir film balance measurements; fluid lipid bilayers, with gel---liquid crystalline phase transitions below physiological temperature, by fluorescence anisotropy; lipid mixing with biomembrane-mimicking vesicles by fluorescence resonance energy transfer; efficient pDNA binding and compaction by ethidium bromide displacement; cationic liposome---nucleic acid complexes (lipoplexes) with large particle sizes (mean diameter ≥ 500 nm) and zeta potentials of positive values by dynamic light scattering and electrophoretic mobility, respectively. The results suggest that well hydrated and elastic cationic lipids forming fluid lamellar assemblies are extremely potent and minimally toxic cytofectins. Second, a comparison was made between 1,3lb2 and two derivatives, one an isomer with a shorter space between the myristoyl chains and the other the monovalent form, in an effort to delineate the biological effects of interchain distance and pH-induced polar headgroup expandability

  16. Mechanistic study of decreased skin penetration using a combination of sonophoresis with sodium fluorescein-loaded PEGylated liposomes with D-limonene

    OpenAIRE

    Ngawhirunpat, Tanasait

    2015-01-01

    Worranan Rangsimawong, Praneet Opanasopit, Theerasak Rojanarata, Tanasait Ngawhirunpat Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand Abstract: The effect of low frequency sonophoresis (SN, 20 kHz) on the skin transport of sodium fluorescein (NaFI)-loaded liposomes was investigated. An in vitro skin penetration study in open and blocked hair follicles was performed, and confocal laser scanning microscopy and scanning electron microscopy were used to visualize the penetra...

  17. Rab11 and Lysotracker Markers Reveal Correlation between Endosomal Pathways and Transfection Efficiency of Surface-Functionalized Cationic Liposome-DNA Nanoparticles.

    Science.gov (United States)

    Majzoub, Ramsey N; Wonder, Emily; Ewert, Kai K; Kotamraju, Venkata Ramana; Teesalu, Tambet; Safinya, Cyrus R

    2016-07-01

    Cationic liposomes (CLs) are widely studied as carriers of DNA and short-interfering RNA for gene delivery and silencing, and related clinical trials are ongoing. Optimization of transfection efficiency (TE) requires understanding of CL-nucleic acid nanoparticle (NP) interactions with cells, NP endosomal pathways, endosomal escape, and events leading to release of active nucleic acid from the lipid carrier. Here, we studied endosomal pathways and TE of surface-functionalized CL-DNA NPs in PC-3 prostate cancer cells displaying overexpressed integrin and neuropilin-1 receptors. The NPs contained RGD-PEG-lipid or RPARPAR-PEG-lipid, targeting integrin, and neuropilin-1 receptors, respectively, or control PEG-lipid. Fluorescence colocalization using Rab11-GFP and Lysotracker enabled simultaneous colocalization of NPs with recycling endosome (Rab11) and late endosome/lysosome (Rab7/Lysotracker) pathways at increasing mole fractions of pentavalent MVL5 (+5 e) at low (10 mol %), high (50 mol %), and very high (70 mol %) membrane charge density (σM). For these cationic NPs (lipid/DNA molar charge ratio, ρchg = 5), the influence of membrane charge density on pathway selection and transfection efficiency is similar for both peptide-PEG NPs, although, quantitatively, the effect is larger for RGD-PEG compared to RPARPAR-PEG NPs. At low σM, peptide-PEG NPs show preference for the recycling endosome over the late endosome/lysosome pathway. Increases in σM, from low to high, lead to decreases in colocalization with recycling endosomes and simultaneous increases in colocalization with the late endosome/lysosome pathway. Combining colocalization and functional TE data at low and high σM shows that higher TE correlates with a larger fraction of NPs colocalized with the late endosome/lysosome pathway while lower TE correlates with a larger fraction of NPs colocalized with the Rab11 recycling pathway. The findings lead to a hypothesis that increases in σM, leading to enhanced

  18. Degradation of functional group of cation exchange nuclear grade resin loaded with different metal ions due to gamma radiation exposure

    International Nuclear Information System (INIS)

    Ion exchange resins undergo degradation due to ionizing radiation while processing the radioactive water treatment. During this process, the cation resin used for this purpose gets loaded with various metal ions and presence of different metal ions in the resin may result into different degradation behaviors of functional group(s) (lowering the capacity). This work deals with the effect of few cations such as H+, Li+, Na+, Cs+ and Cu2+ on the degradation behavior of functional groups of strong acid cation resins exposed in different dose of 60Co gamma ray. Degradations were estimated by measuring the sulphate ion concentration in leach solution. (author)

  19. Innovatives liposomes for overcoming biological barriers

    OpenAIRE

    Chessa, Maura

    2013-01-01

    In this thesis work were prepared and characterized liposomes and liposomes modified with a coating of chitosan called chitosomes. Through these structures were conveyed drugs of natural origin with anti-inflammatory and antioxidant properties: quercetin,phycocyanin and curcumin. The liposomes loading quercetin and phycocyanin are designed for a topical application and were tested on new born pig skin. Liposomes and chitosomes loading curcumin are designed for pulmonary delivery as a cure for...

  20. Preparation of a paclitaxel-loaded cationic nanoemulsome and its biodistribution via direct intratumoral injection.

    Science.gov (United States)

    Xu, Yurui; Asghar, Sajid; Li, Hongying; Chen, Minglei; Su, Zhigui; Xu, Yangfan; Ping, Qineng; Xiao, Yanyu

    2016-06-01

    In this study, a nano-preparation based on nanoemulsome (NES) modified with cetyltrimethylammonium bromide (CTAB) loading paclitaxel (PTX) was designed, and its biodistribution were explored after intratumoral (i.t.) administration on Heps tumor-bearing mice. The PTX-loaded nanoemulsome (PTX-NES) was prepared by using a solvent evaporation method and CTAB, chosen as a cationic material, was absorbed onto the surface of the NES via electrostatic interaction to yield paclitaxel-loaded cationic nanoemulsome (PTX-CTAB-NES). The MTT results exhibited that PTX-CTAB-NES (IC50: 0.50±0.035μg/mL in MCF-7 cells and 0.13±0.048μg/mL in SMMC-7721 cells) had the strongest cytotoxicity compared to Taxol (IC50: 0.88±0.054μg/mL in MCF-7 and 0.15±0.011μg/mL in SMMC-7721) and PTX-NES (IC50: 1.93±0.062μg/mL in MCF-7 and 0.32±0.027μg/mL in SMMC-7721). Body distribution of PTX revealed that the percent of PTX retained in the tumor after i.t. administration of PTX-CTAB-NES (approximately 92.99% at 0.167h and 15.35% at 48h) was higher when compared to that after i.t. injection of Taxol (approximately 58.94% at 0.167h and 0.83% at 48h) or PTX-NES (approximately 83.63% at 0.167h and 6.52% at 48h). Moreover, less PTX accumulated in liver, spleen, kidney, lung and heart after i.t. administration of PTX-CTAB-NES when compared with that after i.v. administration of PTX-CTAB-NES. In conclusion, PTX-CTAB-NES was a prospective in-situ delivery system for the therapy of tumor. PMID:26938323

  1. A Novel Liposome-Based Nanocarrier Loaded with an LPS-dsRNA Cocktail for Fish Innate Immune System Stimulation

    Science.gov (United States)

    Ruyra, Angels; Cano-Sarabia, Mary; MacKenzie, Simon A.; Maspoch, Daniel; Roher, Nerea

    2013-01-01

    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. PMID:24204616

  2. Targeted Liposomal Drug Delivery to Monocytes and Macrophages

    Directory of Open Access Journals (Sweden)

    Ciara Kelly

    2011-01-01

    Full Text Available As the role of monocytes and macrophages in a range of diseases is better understood, strategies to target these cell types are of growing importance both scientifically and therapeutically. As particulate carriers, liposomes naturally target cells of the mononuclear phagocytic system (MPS, particularly macrophages. Loading drugs into liposomes can therefore offer an efficient means of drug targeting to MPS cells. Physicochemical properties including size, charge and lipid composition can have a very significant effect on the efficiency with which liposomes target MPS cells. MPS cells express a range of receptors including scavenger receptors, integrins, mannose receptors and Fc-receptors that can be targeted by the addition of ligands to liposome surfaces. These ligands include peptides, antibodies and lectins and have the advantages of increasing target specificity and avoiding the need for cationic lipids to trigger intracellular delivery. The goal for targeting monocytes/macrophages using liposomes includes not only drug delivery but also potentially a role in cell ablation and cell activation for the treatment of conditions including cancer, atherosclerosis, HIV, and chronic inflammation.

  3. Octreotide-modification enhances the delivery and targeting of doxorubicin-loaded liposomes to somatostatin receptors expressing tumor in vitro and in vivo

    Science.gov (United States)

    Sun, Minjie; Wang, Yu; Shen, Jie; Xiao, Yanyu; Su, Zhigui; Ping, Qineng

    2010-11-01

    Octreotide is believed to be the ligand of somatostatin receptors (SSTRs) which are widely used in tumor diagnosis and clinical therapy. In the present work, a new targeting conjugate, octreotide-polyethylene glycol-phosphatidylethanolamine (Oct-PEG-PE), was developed for the assembling of liposome, and the effect of octreotide-modification on the enhancement of the delivery and targeting of doxorubicin-loaded liposomes was investigated in vitro and in vivo. Oct-PEG-PE was synthesized by a three-step reaction involving two derivative intermediate formations of bis (p-nitrophenyl carbonate)-PEG ((pNP)2-PEG) and pNP-PEG-PE. The Oct-modified and unmodified liposomes (DOX-OL and DOX-CL) were prepared by the ammonium sulfate gradient method. Both drug uptake assay and cell apoptosis assay suggested that DOX-OL noticeably increased the uptake of DOX in SMMC-7721 cells and showed a more significant cytotoxicity, compared with DOX-CL. The effect of DOX-OL was remarkably inhibited by free octreotide. In contrast, no significant difference in drug cytotoxicty was found between DOX-OL and DOX-CL in CHO cells without obvious expression of SSTRs. The study of ex vivo fluorescence tissues imaging of BALB/c mice and in vivo tissue distribution of B16 tumor-bearing mice indicated that DOX-OL caused remarkable accumulation of DOX in melanoma tumors and the pancreas, in which the SSTRs are highly expressed.

  4. In vitro evaluation of inhalable isoniazid-loaded surfactant liposomes as an adjunct therapy in pulmonary tuberculosis.

    Science.gov (United States)

    Chimote, G; Banerjee, R

    2010-07-01

    In this study, exogenous pulmonary surfactant was evaluated as an inhalable drug carrier for antitubercular drug isoniazid (INH). Isoniazid-entrapped liposomes of dipalmitoylphosphatidylcholine (DPPC) (the most abundant lipid of lung surfactant and exogenous surfactant) were developed and evaluated for size, drug entrapment, release, in vitro alveolar deposition, biocompatibility, antimycobacterial activity, and pulmonary surfactant action. Isoniazid-entrapped DPPC liposomes were about 750 nm in diameter and had entrapment efficiency of 36.7% +/- 1.8%. Sustained release of INH from DPPC liposomes was observed over 24 h. In vitro alveolar deposition efficiency using the twin impinger exhibited approximately 25-27% INH deposition in the alveolar chamber upon one minute nebulization using a jet nebulizer. At 37 degrees C, the formulation had better pulmonary surfactant function with quicker reduction of surface tension on adsorption (36.7 +/- 0.4 mN/m) than DPPC liposomes (44.7 +/- 0.6 mN/m) and 87% airway patency was exhibited by the formulation in a capillary surfactometer. The formulation was biocompatible and had antimycobacterial activity. The isoniazid-entrapped DPPC liposomes could fulfill the dual purpose of pulmonary drug delivery and alveolar stabilization due to antiatelectatic effect of the surfactant action which can improve the reach of antitubercular drug INH to the alveoli. PMID:20524179

  5. Synthesis of diethylenetriaminepentaacetic acid conjugated inulin and utility for cellular uptake of liposomes

    International Nuclear Information System (INIS)

    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 67Ga3+ or 111In3+ 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

  6. Enhanced hypoglycemic effect of biotin-modified liposomes loading insulin: effect of formulation variables, intracellular trafficking, and cytotoxicity

    Science.gov (United States)

    Zhang, Xingwang; Qi, Jianping; Lu, Yi; Hu, Xiongwei; He, Wei; Wu, Wei

    2014-04-01

    Peroral protein/peptide delivery has been one of the most challenging, but encouraging topics in pharmaceutics. This article was intended to explore the potential of biotin-modified liposomes (BLPs) as oral insulin delivery carriers. By incorporating biotin-DSPE into the lipid bilayer, we prepared BLPs using reverse evaporation/sonication method. We investigated hypoglycemic effects in normal rats after oral administration of BLPs, and the possible absorption mechanism by a series of in vitro tests. The relative pharmacological bioavailability of BLPs was up to 11.04% that was as much as 5.28 folds of conventional liposomes (CLPs). The results showed that the enhanced oral absorption of insulin mainly attributed to biotin ligand-mediated endocytosis. The results provided proof of BLPs as effective carriers for oral insulin delivery.

  7. Complexes containing cationic and anionic pH-sensitive liposomes: comparative study of factors influencing plasmid DNA gene delivery to tumors

    OpenAIRE

    Chen Y; Sun J; Lu Y.; Tao C; Huang JB; Zhang H; Yu Y; Zou H; Gao J; Zhong YQ

    2013-01-01

    Yan Chen,* Ji Sun,* Ying Lu, Chun Tao, Jingbin Huang, He Zhang, Yuan Yu, Hao Zou, Jing Gao, Yanqiang Zhong Department of Pharmaceutical Science, School of Pharmacy, The Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: pH-sensitive liposomes represent an effective gene vector in cancer therapy. However, their use is greatly hampered by their relatively low transfection efficiency. To improve the transfectio...

  8. Complexes containing cationic and anionic pH-sensitive liposomes: comparative study of factors influencing plasmid DNA gene delivery to tumors

    OpenAIRE

    Zhong, Yanqiang

    2013-01-01

    Yan Chen,* Ji Sun,* Ying Lu, Chun Tao, Jingbin Huang, He Zhang, Yuan Yu, Hao Zou, Jing Gao, Yanqiang Zhong Department of Pharmaceutical Science, School of Pharmacy, The Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: pH-sensitive liposomes represent an effective gene vector in cancer therapy. However, their use is greatly hampered by their relatively low transfection efficiency. To improve the tran...

  9. HTGR fuel development: loading of uranium on carboxylic acid cation-exchange resins using solvent extraction of nitrate

    International Nuclear Information System (INIS)

    The reference fuel kernel for recycle of 233U to HTGR's (High-Temperature Gas-Cooled Reactors) is prepared by loading carboxylic acid cation-exchange resins with uranium and carbonizing at controlled conditions. The purified 233UO2(NO3)2 solution from a fuel reprocessing plant contains excess HNO3 (NO3-/U ratio of approximately 2.2). The reference flowsheet for a 233U recycle fuel facility at Oak Ridge uses solvent extraction of nitrate by a 0.3 M secondary amine in a hydrocarbon diluent to prepare acid-deficient uranyl nitrate. This nitrate extraction, along with resin loading and amine regeneration steps, was demonstrated in 14 runs. No significant operating difficulties were encountered. The process is controlled via in-line pH measurements for the acid-deficient uranyl nitrate solutions. Information was developed on pH values for uranyl nitrate solution vs NO3-/U mole ratios, resin loading kinetics, resin drying requirements, and other resin loading process parameters. Calculations made to estimate the capacities of equipment that is geometrically safe with respect to control of nuclear criticality indicate 100 kg/day or more of uranium for single nitrate extraction lines with one continuous resin loading contactor or four batch loading contactors. (auth)

  10. Non-invasive detection of macrophages in atheroma using a radiocontrast-loaded phosphatidylserine-containing liposomal contrast agent for computed tomography

    Science.gov (United States)

    Kee, Patrick; Bagalkot, Vaishali; Johnson, Evan; Danila, Delia

    2014-01-01

    Purpose Macrophage plays an important role in plaque destabilization in atherosclerosis. By harnessing the affinity of macrophages to certain phospholipid species, a liposomal contrast agent containing phosphatidylserine (PS) and computed tomographic (CT) contrast agent was prepared and evaluated for CT imaging of plaque-associated macrophages in rabbit models of atherosclerosis. Procedures Liposomes containing PS and iodixanol were evaluated for their physicochemical characteristics, in vitro macrophage uptake, in vivo blood pool clearance and organ distribution. Plaque enhancement in the aorta was imaged with computed tomography (CT) in two atherosclerotic rabbit models. Results In vitro macrophage uptake of PS-liposomes increased with increasing amount of PS in the liposomes. Overall clearance of PS-liposomes was more rapid than control liposomes. Smaller PS-liposomes (d = 112 ± 4 nm) were more effective than control liposomes of similar size or larger control and PS-liposomes (d = 172 ± 17 nm) in enhancing aortic plaques in both rabbit models. Conclusions Proper liposomal surface modification and appropriate sizing are important determinant for CT-based molecular imaging of macrophages in atheroma. PMID:25301703

  11. Anti-inflammatory activity of cationic lipids

    OpenAIRE

    Filion, Mario C; Phillips, Nigel C

    1997-01-01

    The effect of liposome phospholipid composition has been assumed to be relatively unimportant because of the presumed inert nature of phospholipids.We have previously shown that cationic liposome formulations used for gene therapy inhibit, through their cationic component, the synthesis by activated macrophages of the pro-inflammatory mediators nitric oxide (NO) and tumour necrosis factor-α (TNF-α).In this study, we have evaluated the ability of different cationic lipids to reduce footpad inf...

  12. Controllable labelling of stem cells with a novel superparamagnetic iron oxide-loaded cationic nanovesicle for MR imaging

    International Nuclear Information System (INIS)

    To investigate the feasibility of highly efficient and controllable stem cell labelling for cellular MRI. A new class of cationic, superparamagnetic iron oxide nanoparticle (SPION)-loaded nanovesicles was synthesised to label rat bone marrow mesenchymal stem cells without secondary transfection agents. The optimal labelling conditions and controllability were assessed, and the effect of labelling on cell viability, proliferation activity and multilineage differentiation was determined. In 18 rats, focal ischaemic cerebral injury was induced and the rats randomly injected with 1 x 106 cells labelled with 0-, 8- or 20-mV nanovesicles (n = 6 each). In vivo MRI was performed to follow grafted cells in contralateral striata, and results were correlated with histology. Optimal cell labelling conditions involved a concentration of 3.15 μg Fe/mL nanovesicles with 20-mV positive charge and 1-h incubation time. Labelling efficiency showed linear change with an increase in the electric potentials of nanovesicles. Labelling did not affect cell viability, proliferation activity or multilineage differentiation capacity. The distribution and migration of labelled cells could be detected by MRI. Histology confirmed that grafted cells retained the label and remained viable. Stem cells can be effectively and safely labelled with cationic, SPION-loaded nanovesicles in a controllable way for cellular MRI. (orig.)

  13. Liposomes Loaded with Paclitaxel and Modified with Novel Triphenylphosphonium-PEG-PE Conjugate Possess Low Toxicity, Target Mitochondria and Demonstrate Enhanced Antitumor Effects In Vitro and In Vivo

    OpenAIRE

    Biswas, Swati; Dodwadkar, Namita S.; Deshpande, Pranali P.; Torchilin, Vladimir P.

    2012-01-01

    Previously, stearyl triphenylphosphonium (STPP)-modified liposomes (STPP-L) were reported to target mitochondria. To overcome a non-specific cytotoxicity of STPP-L, we synthesized a novel polyethylene glycol- phosphatidylethanolamine (PEG-PE) conjugate with the TPP group attached to the distal end of the PEG block (TPP-PEG-PE). This conjugate was incorporated into the liposomal lipid bilayer, and the modified liposomes were studied for their toxicity, mitochondrial targeting, and efficacy in ...

  14. In situ Delivery of Tumor Antigen- and Adjuvant-Loaded Liposomes Boosts Antigen-Specific T-Cell Responses by Human Dermal Dendritic Cells.

    Science.gov (United States)

    Boks, Martine A; Bruijns, Sven C M; Ambrosini, Martino; Kalay, Hakan; van Bloois, Louis; Storm, Gert; de Gruijl, Tanja; van Kooyk, Yvette

    2015-11-01

    Dendritic cells (DCs) have an important role in tumor control via the induction of tumor-specific T-cell responses and are therefore an ideal target for immunotherapy. The human skin is an attractive site for tumor vaccination as it contains various DC subsets. The simultaneous delivery of tumor antigen with an adjuvant is beneficial for cross-presentation and the induction of tumor-specific T-cell responses. We therefore developed liposomes that contain the melanoma-associated antigen glycoprotein 100280-288 peptide and Toll-like receptor 4 (TLR4) ligand monophosphoryl lipid A (MPLA) as adjuvant. These liposomes are efficiently taken up by monocyte-derived DCs, and antigen presentation to CD8(+) T cells was significantly higher with MPLA-modified liposomes as compared with non-modified liposomes or the co-administration of soluble MPLA. We used a human skin explant model to evaluate the efficiency of intradermal delivery of liposomes. Liposomes were efficiently taken up by CD1a(+) and especially CD14(+) dermal DCs. Induction of CD8(+) T-cell responses by emigrated dermal DCs was significantly higher when MPLA was incorporated into the liposomes as compared with non-modified liposomes or co-administration of soluble MPLA. Thus, the modification of antigen-carrying liposomes with TLR ligand MPLA significantly enhances tumor-specific T-cell responses by dermal DCs and is an attractive vaccination strategy in human skin. PMID:26083554

  15. Remote loading of doxorubicin into liposomes by transmembrane pH gradient to reduce toxicity toward H9c2 cells

    Directory of Open Access Journals (Sweden)

    Mohamed Alyane

    2016-03-01

    Full Text Available The use of doxorubicin (DOX is limited by its dose-dependent cardiotoxicity. Entrapped DOX in liposome has been shown to reduce cardiotoxicity. Results showed that about 92% of the total drug was encapsulated in liposome. The release experiments showed a weak DOX leakage in both culture medium and in PBS, more than 98% and 90% of the encapsulated DOX respectively was still retained in liposomes after 24 h of incubation. When the release experiments were carried out in phosphate buffer pH5.3, the leakage of DOX from liposomes reached 37% after 24 h of incubation. Evaluation of cellular uptake of the liposomal DOX indicated the possible endocytosis of liposomes because the majority of visible fluorescence of DOX was mainly in the cytoplasm, whereas the nuclear compartment showed a weak intensity. When using unloaded fluorescent-liposomes, the fluorescence was absent in nuclei suggests that liposomes cannot cross the nuclear membrane. MTT assay and measurement of LDH release suggest that necrosis is the form of cellular death predominates in H9c2 cells exposed to high doses of DOX, while for weak doses apoptosis could be the predominate form. Entrapped DOX reduced significantly DOX toxicity after 3 and 6 h of incubation, but after 20 h entrapped DOX is more toxic than free one.

  16. Removal of cationic and anionic dyes by immobilised titanium dioxide loaded activated carbon

    International Nuclear Information System (INIS)

    Combination of adsorption and photodegradation processes induces strong beneficial effects in dye removals. Adding high adsorption capacity activated carbon to photoactive titanium dioxide is an attractive solution due to their potential in removing dyes of diverse chemical characteristics. Recently, immobilisation has been an acceptable approach to overcome the drawbacks encountered with powder suspensions. The present study involves the removals of Victoria Blue R (VBR), a cationic dye and Indigo Carmine (IC), an anionic using approximately one gram of immobilised titanium dioxide (TiO2), activated carbon (AC) and mixture titanium dioxide/ activated carbon (TiO2/ AC) from 200 mL solution at the concentration of 20 ppm under UV illumination for 4 hours. Comparisons were made in terms of their removal efficiency by applying first-order kinetics model. Immobilised TiO2 showed total removal of IC in 40 minutes whereas only 44 % of VBR was removed in 2 hours. On the other hand, in the case of immobilised AC, about 87 % of VBR and 6 % of IC were removed in 2 hours. The results obtained using immobilised TiO2/ AC proved the prominence of this immobilised sample in dealing with VBR and IC by achieving 95 % and 62 % removal respectively in 2 hours. (author)

  17. 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.

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

    International Nuclear Information System (INIS)

    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.

  19. Elaboration of Sterically Stabilized Liposomes for S-Nitrosoglutathione Targeting to Macrophages.

    Science.gov (United States)

    Diab, R; Virriat, A S; Ronzani, C; Fontanay, S; Grandemange, S; Elaissari, A; Foliguet, B; Maincent, P; Leroy, P; Duvaj, R E; Rihn, B H; Joubert, O

    2016-01-01

    S-nitrosoglutathione (GSNO) is a potential therapeutic for infectious disease treatment because of its pivotal role in macrophage-mediated inflammatory responses and host defense in addition to direct antibacterial activities. In this study, sterically stabilized cationic liposomes (SSCL) and sterically stabilized anionic liposomes (SSAL) were developed as nanocarriers for macrophage targeting. Elaborated liposomes were characterized in terms of size, zeta potential, morphology, encapsulation efficiency, in vitro drug release behavior and cytotoxicity. Their versatility in targeting monocytes/macrophages was determined by confocal laser scanning microscopy and transmission electron microscopy. Flow cytometry revealed that cellular uptake of both SSCL and SSAL was governed by several endocytic clathrin- and caveolae-dependent mechanisms. Quantitative assessments of intracellular nitric oxide demonstrated highly efficient uptake of GSNO-loaded SSCL that was twenty-fold higher than that of GSNO-free molecules. GSNO-loaded SSCL displayed strong bacteriostatic effects on Staphylococcus aureus and Pseudomonas aeruginosa, which can be involved in pulmonary infectious diseases. These results reveal the potential of liposomal GSNO as an anti-infective therapeutic due to its macrophage targeting capacity and direct antibacterial effects. PMID:27301185

  20. A Review on Composite Liposomal Technologies for Specialized Drug Delivery

    Directory of Open Access Journals (Sweden)

    Maluta S. Mufamadi

    2011-01-01

    Full Text Available The combination of liposomes with polymeric scaffolds could revolutionize the current state of drug delivery technology. Although liposomes have been extensively studied as a promising drug delivery model for bioactive compounds, there still remain major drawbacks for widespread pharmaceutical application. Two approaches for overcoming the factors related to the suboptimal efficacy of liposomes in drug delivery have been suggested. The first entails modifying the liposome surface with functional moieties, while the second involves integration of pre-encapsulated drug-loaded liposomes within depot polymeric scaffolds. This attempts to provide ingenious solutions to the limitations of conventional liposomes such as short plasma half-lives, toxicity, stability, and poor control of drug release over prolonged periods. This review delineates the key advances in composite technologies that merge the concepts of depot polymeric scaffolds with liposome technology to overcome the limitations of conventional liposomes for pharmaceutical applications.

  1. Engineering of an Inhalable DDA/TDB Liposomal Adjuvant

    DEFF Research Database (Denmark)

    Ingvarsson, Pall Thor; Yang, Mingshi; Mulvad, Helle;

    2013-01-01

    The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB).......The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB)....

  2. 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.

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

    OpenAIRE

    Parvin Zakeri-Milani; Hadi Valizadeh; Saeed Ghanbarzadeh

    2013-01-01

    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 siro...

  4. 两亲性壳聚糖包覆紫杉醇脂质体的制备及体外释放研究%Preparation and in vitro Release of Paclitaxel Loaded Liposomes Modified with Amphiphilic Chitosan Derivatives

    Institute of Scientific and Technical Information of China (English)

    刁雨辉; 霍美蓉; 吕霖; 周建平

    2012-01-01

    Objective: To prepare paclitaxel loaded liposomes modified with amphiphilic chitosan deirvatives (N-octyl-N,O-carboxymethyl chitosan, OCC), and investigate their characteristics and release behavior in vitro. Methods Paclitaxel loaded liposomes modified with or without OCC (PTX-LP, PTX-LP-OCC) were prepared using an ethanol-based proliposome technology. Particle size and zeta potential of the liposomes were determined with Zetasizer 3000HSa The morphology was observed by a transmission electron microscope (TEM) technology. Stability of liposomes was evaluated by determining the particle size and drug leakage from liposomes. Finally, the in vitro release profiles of paclitaxel from PTX-LP and PTX-LP-OCC were evaluated using the bulk-equilibrium reverse dialysis bag technique Results Paclitaxel loaded liposomes were successfully prepared with an average diameter of 2365 nm and zeta potential of -31.4mV. The encapsulation efficiency was 895%. After OCC modification, there was no significant change in encapsulation efficiency, but the particle size and zeta potential significantly increased. As compared to PTX-LP, PTX-LP-OCC possessed better stability and lower burst release Conclusion: Liposome modified with amphiphilic chitosan derivatives is a promising carrier for anticancer drug delivery.%目的:制备两亲性壳聚糖N-辛基-N,O-羧甲基壳聚糖包覆紫杉醇脂质体(PTX-LP-OCC),并考察其理化性质及体外释放行为.方法:采用基于乙醇的前体脂质体法制备紫杉醇脂质体并以OCC包覆,并以普通脂质体(PTX-LP)为对照,测定其包封率、粒径大小、电位,观测其形态及稳定性,然后采用全体液平衡反向透析法研究体外释放行为.结果:紫杉醇脂质体包封率为89.5%,粒径为236.5 nm,Zeta电位为-31.4 mV,多糖包覆修饰后药物包封率无显著变化,粒径及Zeta电位显著增加,脂质体稳定性显著提高,药物释放呈缓释特征,且突释显著降低.结论:两亲性壳聚糖包

  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. Zinc ionophore activity of quercetin and epigallocatechin-gallate: from Hepa 1-6 cells to a liposome model.

    Science.gov (United States)

    Dabbagh-Bazarbachi, Husam; Clergeaud, Gael; Quesada, Isabel M; Ortiz, Mayreli; O'Sullivan, Ciara K; Fernández-Larrea, Juan B

    2014-08-13

    Labile zinc, a tiny fraction of total intracellular zinc that is loosely bound to proteins and easily interchangeable, modulates the activity of numerous signaling and metabolic pathways. Dietary plant polyphenols such as the flavonoids quercetin (QCT) and epigallocatechin-gallate act as antioxidants and as signaling molecules. Remarkably, the activities of numerous enzymes that are targeted by polyphenols are dependent on zinc. We have previously shown that these polyphenols chelate zinc cations and hypothesized that these flavonoids might be also acting as zinc ionophores, transporting zinc cations through the plasma membrane. To prove this hypothesis, herein, we have demonstrated the capacity of QCT and epigallocatechin-gallate to rapidly increase labile zinc in mouse hepatocarcinoma Hepa 1-6 cells as well as, for the first time, in liposomes. In order to confirm that the polyphenols transport zinc cations across the plasma membrane independently of plasma membrane zinc transporters, QCT, epigallocatechin-gallate, or clioquinol (CQ), alone and combined with zinc, were added to unilamellar dipalmitoylphosphocholine/cholesterol liposomes loaded with membrane-impermeant FluoZin-3. Only the combinations of the chelators with zinc triggered a rapid increase of FluoZin-3 fluorescence within the liposomes, thus demonstrating the ionophore action of QCT, epigallocatechin-gallate, and CQ on lipid membrane systems. The ionophore activity of dietary polyphenols may underlay the raising of labile zinc levels triggered in cells by polyphenols and thus many of their biological actions. PMID:25050823

  7. Topical and mucosal liposomes for vaccine delivery.

    Science.gov (United States)

    Romero, Eder Lilia; Morilla, Maria Jose

    2011-01-01

    Mucosal (and in minor extent transcutanous) stimulation can induce local or distant mucosa secretory IgA. Liposomes and other vesicles as mucosal and transcutaneous adjuvants are attractive alternatives to parenteral vaccination. Liposomes can be massively produced under good manufacturing practices and stored for long periods, at high antigen/vesicle mass ratios. However, their uptake by antigen-presenting cells (APC) at the inductive sites remains as a major challenge. As neurotoxicity is a major concern in intranasal delivery, complexes between archaeosomes and calcium as well as cationic liposomes complexed with plasmids encoding for antigenic proteins could safely elicit secretory and systemic antigen-specific immune responses. Oral bilosomes generate intense immune responses that remain to be tested against challenge, but the admixing with toxins or derivatives is mandatory to reduce the amount of antigen. Most of the current experimental designs, however, underestimate the mucus blanket 100- to 1000-fold thicker than a 100-nm diameter liposome, which has first to be penetrated to access the underlying M cells. Overall, designing mucoadhesive chemoenzymatic resistant liposomes, or selectively targeted to M cells, has produced less relevant results than tailoring the liposomes to make them mucus penetrating. Opposing, the nearly 10 µm thickness stratum corneum interposed between liposomes and underlying APC can be surpassed by ultradeformable liposomes (UDL), with lipid matrices that penetrate up to the limit with the viable epidermis. UDL made of phospholipids and detergents, proved to be better transfection agents than conventional liposomes and niosomes, without the toxicity of ethosomes, in the absence of classical immunomodulators. PMID:21360692

  8. Characterization of biosurfactant-containing liposomes and their efficiency for gene transfection.

    Science.gov (United States)

    Ueno, Yoshinobu; Hirashima, Naohide; Inoh, Yoshikazu; Furuno, Tadahide; Nakanishi, Mamoru

    2007-01-01

    Recently we showed significance of biosurfactants in the field of non-viral vectors for gene transfection. There, a biosurfactant, mannosylerythritol lipid A (MEL-A), especially increased the efficiency of gene transfection mediated with cationic liposomes. However, the molecular mechanism has not been well-understood yet. Here, through the examination of the ability of cationic liposomes containing an MEL (MEL-A, MEL-B or MEL-C) for important transfectional processes of the DNA capsulation and the membrane fusion with anionic liposomes, we found that MEL-A-containing liposomes increased both processes, but that MEL-B and MEL-C-containing liposomes just increased either of them. The results indicated that these kinds of the physicochemical properties in MEL-A-containing liposomes are able to increase the efficiency of liposome-mediated gene transfection. PMID:17202680

  9. Liposomes of terbutaline sulphate: in vitro and in vivo studies.

    Science.gov (United States)

    Joshi, M R; Misra, A N

    1999-09-01

    In vitro studies were conducted to understand the comparative drug diffusion pattern, across artificial membrane, of the drug and of the prepared liposomes of different liposomal membrane composition. In vivo studies were carried out to determine the extent and time-course of pulmonary tissue uptake of administered liposomes containing terbutaline sulphate(TER) on rat lungs. In vitro studies revealed that the drug released from the prepared liposomes obeys Higuchi's diffusion controlled model. Different loading doses and release patterns of drug from the liposomes can be obtained by altering the PC:CHOL ratio and incorporation of cholesterol was found to reduce permeability of the membrane. Similarly drug absorption in vivo in rat's lung following intratracheal instillation, prolonged over 12 hr by liposomal entrapment of TER. The findings of present investigation indicated that liposomally encapsulated TER can be used for pulmonary delivery for maximizing the therapeutic efficacy and reducing undesirable side effects. PMID:10687283

  10. Biopharmaceutical evaluation of epigallocatechin gallate-loaded cationic lipid nanoparticles (EGCG-LNs): In vivo, in vitro and ex vivo studies.

    Science.gov (United States)

    Fangueiro, Joana F; Calpena, Ana C; Clares, Beatriz; Andreani, Tatiana; Egea, Maria A; Veiga, Francisco J; Garcia, Maria L; Silva, Amélia M; Souto, Eliana B

    2016-04-11

    Cationic lipid nanoparticles (LNs) have been tested for sustained release and site-specific targeting of epigallocatechin gallate (EGCG), a potential polyphenol with improved pharmacological profile for the treatment of ocular pathologies, such as age-related macular edema, diabetic retinopathy, and inflammatory disorders. Cationic EGCG-LNs were produced by double-emulsion technique; the in vitro release study was performed in a dialysis bag, followed by the drug assay using a previously validated RP-HPLC method. In vitro HET-CAM study was carried out using chicken embryos to determine the potential risk of irritation of the developed formulations. Ex vivo permeation profile was assessed using rabbit cornea and sclera isolated and mounted in Franz diffusion cells. The results show that the use of cationic LNs provides a prolonged EGCG release, following a Boltzmann sigmoidal profile. In addition, EGCG was successfully quantified in both tested ocular tissues, demonstrating the ability of these formulations to reach both anterior and posterior segment of the eye. The pharmacokinetic study of the corneal permeation showed a first order kinetics for both cationic formulations, while EGCG-cetyltrimethylammonium bromide (CTAB) LNs followed a Boltzmann sigmoidal profile and EGCG-dimethyldioctadecylammonium bromide (DDAB) LNs a first order profile. Our studies also proved the safety and non-irritant nature of the developed LNs. Thus, loading EGCG in cationic LNs is recognised as a promising strategy for the treatment of ocular diseases related to anti-oxidant and anti-inflammatory pathways. PMID:26921515

  11. 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

  12. Liposomes as a gene delivery system

    Directory of Open Access Journals (Sweden)

    C. Ropert

    1999-02-01

    Full Text Available Gene therapy is an active field that has progressed rapidly into clinical trials in a relatively short time. The key to success for any gene therapy strategy is to design a vector able to serve as a safe and efficient gene delivery vehicle. This has encouraged the development of nonviral DNA-mediated gene transfer techniques such as liposomes. Many liposome-based DNA delivery systems have been described, including molecular components for targeting given cell surface receptors or for escaping from the lysosomal compartment. Another recent technology using cationic lipids has been evaluated and has generated substantial interest in this approach to gene transfer.

  13. Novel fluorescence method to visualize antibody-dependent hydrogen peroxide-associated "killing" of liposomes by phagocytes.

    OpenAIRE

    Petty, H R; Francis, J W

    1985-01-01

    We have developed a new methodology to examine effector-cell-mediated immune attack using liposomes as targets. Hydrogen-peroxide-associated killing of liposomes was observed with fluorescence intensification microscopy. Liposomes were composed of 98-99 mol % egg phosphatidylcholine and 1-2 mol % dinitrophenyl lipid hapten. Anti-dinitrophenyl IgG antibody was used to opsonize liposomes. Liposomes were loaded with dihydroxymandelic acid (DHMA) and peroxidase. Macrophage- or neutrophil-mediated...

  14. 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.

  15. Surface Modification of Liposomal Vaccines by Peptide Conjugation

    Directory of Open Access Journals (Sweden)

    Hazra M2

    2011-01-01

    Full Text Available The aim of the present work was to prepare liposomal vaccine formulation by incorporating naked plasmid DNA that can trigger humoral and cell mediated protective immunity against infection. For these cationic lipids like dimyristoyl phosphatidylcholine (DMPC, dioleyl phosphatidyl ethanolamine (DOPE, [1, 2 – dioleyloxy -3-(trimethyl ammonium propane] (DOTAP, were taken in the ratio of 4:2:1 respectively. The liposomal formulations thus prepared were surface modified by peptide conjugation with the help of EDC and NHS. Physical characterization of liposomal formulationswas done by estimating the average size distribution, which gives an average liposomal size of 53.0nm. Concentration of peptide bound liposomes wasestimated by Lowry method which entails that bound protein concentration was 30.5 µg/ml.

  16. LIPOSOMES: AN OVERVIEW

    Directory of Open Access Journals (Sweden)

    Prabhakar Vishvakrama

    2014-06-01

    Full Text Available The discovery of liposome or lipid vesicle emerged from self forming enclosed lipid bi-layer upon hydration. Liposome drug delivery systems have played a significant role in formulation of potent drug to improve therapeutics. Recently the liposome formulations are targeted to reduce toxicity and increase accumulation at the target site. There are several new methods of liposome preparation based on lipid drug interaction and liposome disposition mechanism including the inhibition of rapid clearance of liposome by controlling particle size, charge and surface hydration. Most clinical applications of liposomal drug delivery are targeting to tissue with or without expression of target recognition molecules on lipid membrane. The liposomes are characterized with respect to physical, chemical and biological parameters. The sizing of liposome is also critical parameter which helps characterize the liposome which is usually performed by sequential extrusion at relatively low pressure through polycarbonate membrane (PCM. This mode of drug delivery lends more safety and efficacy to administration of several classes of drugs like antiviral, antifungal, antimicrobial, vaccines, anti tubercular drugs and gene therapeutics. Present applications of the liposomes are in the immunology, dermatology, vaccine adjuvant, eye disorders, brain targeting, infective disease and in tumour therapy. The new developments in this field are the specific binding properties of a drug-carrying liposome to a target cell such as a tumor cell and specific molecules in the body (antibodies, proteins, peptides etc.; stealth liposomes which are especially being used as carriers for hydrophilic (water soluble anticancer drugs like doxorubicin, mitoxantrone; and bisphosphonate- liposome mediated depletion of macrophages. This review would be a help to the researchers working in the area of liposomal drug delivery.

  17. Preliminary Studies on X-Ray-sensitive Liposome

    Institute of Scientific and Technical Information of China (English)

    MENG Fan-xu; XU Hua-ping; QI Yan-fei; XU Kun; SONG Xiu-ling; NIU Shu; LI Juan

    2012-01-01

    The synthesis of a new type of X-ray-sensitive compound “di-(1-hydroxylundecyl)diselenide” and its application in the preparation of a new type of liposome with X-ray sensitivity was reported.This new liposome was synthesized to encapsulate doxorubicin hydrochloride(Dox),with its physical and chemical properties,stability,and radiation sensitivity determined.Based on the pH-gradient method,liposomal Dox was prepared via ultrasonic emulsification and then purified on a Sephadex G50 mini-column.UV spectrophotometry and liquid chromatography were used to detect the encapsulation efficiency and radiation sensitivity of the Dox-loaded liposome.The results show that through changes in release rate,this liposome shows a relative radiosensitivity.In terms of radiation sensitivity,the drug leak rate of the X-ray-sensitive Dox-loaded liposome increased gradually and peaked at 65.4% under the X-ray radiation of a dose of 10 Gy or more than 10 Gy,which is significantly different from that of ordinary liposomes.Meanwhile,X-ray-sensitive Dox-loaded liposome has a good dispersion stability,with an average particle size of approximate 120 nm.The efficiency of this liposome encapsulating Dox was 75.84%,slightly lower than that of ordinary liposomes.The X-ray-sensitive Dox-loaded liposome exhibited suspension stability within 30 d of storage at 4 ℃,without visible precipitation.Di-(1-hydroxylundecyl)diselenide is safe and noncytotoxic and compared with those of synthetic phospholipids its synthesis is low cost and does not require complex conditions.

  18. Covalent immobilization of liposomes on plasma functionalized metallic surfaces.

    Science.gov (United States)

    Mourtas, S; Kastellorizios, M; Klepetsanis, P; Farsari, E; Amanatides, E; Mataras, D; Pistillo, B R; Favia, P; Sardella, E; d'Agostino, R; Antimisiaris, S G

    2011-05-01

    A method was developed to functionalize biomedical metals with liposomes. The novelty of the method includes the plasma-functionalization of the metal surface with proper chemical groups to be used as anchor sites for the covalent immobilization of the liposomes. Stainless steel (SS-316) disks were processed in radiofrequency glow discharges fed with vapors of acrylic acid to coat them with thin adherent films characterized by surface carboxylic groups, where liposomes were covalently bound through the formation of amide bonds. For this, liposomes decorated with polyethylene glycol molecules bearing terminal amine-groups were prepared. After ensuring that the liposomes remain intact, under the conditions applying for immobilization; different attachment conditions were evaluated (incubation time, concentration of liposome dispersion) for optimization of the technique. Immobilization of calcein-entrapping liposomes was evaluated by monitoring the percent of calcein attached on the surfaces. Best results were obtained when liposome dispersions with 5mg/ml (liposomal lipid) concentration were incubated on each disk for 24h at 37°C. The method is proposed for developing drug-eluting biomedical materials or devices by using liposomes that have appropriate membrane compositions and are loaded with drugs or other bioactive agents. PMID:21273051

  19. Peptide-Coated Liposomal Fasudil Enhances Site Specific Vasodilation in Pulmonary Arterial Hypertension

    OpenAIRE

    Nahar, Kamrun; Absar, Shahriar; Gupta, Nilesh; Kotamraju, Venkata Ramana; McMurtry, Ivan F.; Oka, Masahiko; Komatsu, Masanobu; Nozik-Grayck, Eva; Ahsan, Fakhrul

    2014-01-01

    This study sought to develop a liposomal delivery system of fasudil—an investigational drug for the treatment of pulmonary arterial hypertension (PAH)—that will preferentially accumulate in the PAH lungs. Liposomal fasudil was prepared by film-hydration method, and the drug was encapsulated by active loading. The liposome surface was coated with a targeting moiety, CARSKNKDC, a cyclic peptide; the liposomes were characterized for size, polydispersity index, zeta potential, and storage and neb...

  20. Tetanus toxoid-loaded cationic non-aggregated nanostructured lipid particles triggered strong humoral and cellular immune responses.

    Science.gov (United States)

    Kaur, Amandeep; Jyoti, Kiran; Rai, Shweta; Sidhu, Rupinder; Pandey, Ravi Shankar; Jain, Upendra Kumar; Katyal, Anju; Madan, Jitender

    2016-05-01

    In the present investigation, non-aggregated cationic and unmodified nanoparticles (TT-C-NLPs4 and TT-NLPs1) were prepared of about 49.2 ± 6.8-nm and 40.8 ± 8.3-nm, respectively. In addition, spherical shape, crystalline architecture and cationic charge were also noticed. Furthermore, integrity and conformational stability of TT were maintained in both TT-C-NLPs4 and TT-NLPs1, as evidenced by symmetrical position of bands and superimposed spectra, respectively in SDS-PAGE and circular dichroism. Cellular uptake in RAW264.7 cells indicating the concentration-dependent internalisation of nanoparticles. Qualitatively, CLSM exhibited enhanced cellular uptake of non-aggregated TT-C-NLPs4 owing to interaction with negatively charged plasma membrane and clevaloe mediated/independent endocytosis. In last, in vivo immunisation with non-aggregated TT-C-NLPs4 elicited strong humoral (anti-TT IgG) and cellular (IFN-γ) immune responses at day 42, as compared to non-aggregated TT-NLPs1 and TT-Alum following booster immunisation at day 14 and 28. Thus, non-aggregated cationic lipid nanoparticles may be a potent immune-adjuvant for parenteral delivery of weak antigens. PMID:27056086

  1. Mannosylated liposomes for targeted gene delivery

    Directory of Open Access Journals (Sweden)

    Kong F

    2012-02-01

    Full Text Available Fansheng Kong1, Fang Zhou1, Linfu Ge1, Ximin Liu1, Yong Wang21Department of Hematology, 2Department of Rehabilitation and Physiotherapy, General Hospital of Ji'nan Command, PLA, Ji'nan, People's Republic of ChinaBackground: Liposomes can be modified with different ligands to control their biological properties, such as longevity, targeting ability, and intracellular penetration, in a desired fashion. The aim of this study was to modify liposomes with a novel mannosylated polyethylene glycol-phosphatidylethanolamine (M-PEG-PE ligand to achieve active targeted gene delivery.Methods: Rat Kupffer cells were isolated and used as model cells for in vitro evaluation of cytotoxicity and transfection efficiency. The modified liposomes were intravenously injected into the rats, and Kupffer cells were isolated and analyzed by flow cytometry for in vivo gene delivery and expression.Results: The M-PEG-PE-modified liposome-enhanced green fluorescence protein plasmid (M-PEG-PE-Lipo-pEGFP complexes had a particle size of 237 nm and a loading efficiency of 90%. The M-PEG-PE-Lipo-pEGFP complexes displayed remarkably higher transfection efficiency than unmodified Lipo-pEGFP, both in vitro (51%–30% and in vivo (43%–27%.Conclusion: M-PEG-PE could function as an excellent active targeting ligand, and M-PEG-PE-modified liposomes could be promising active targeted drug delivery vectors.Keywords: gene delivery, active targeting, mannosylated, polyethylene glycol, phosphatidylethanolamine, liposomes

  2. A simple liposome assay for the screening of zinc ionophore activity of polyphenols.

    Science.gov (United States)

    Clergeaud, Gael; Dabbagh-Bazarbachi, Husam; Ortiz, Mayreli; Fernández-Larrea, Juan B; O'Sullivan, Ciara K

    2016-04-15

    An efficient liposomal system for screening the zinc ionophore activity of a selected library consisting of the most relevant dietary polyphenols is presented. The zinc ionophore activity was demonstrated by exploring the use of zinc-specific fluorophore FluoZin-3 loaded liposomes as simple membrane tools that mimic the cell membrane. The zinc ionophore activity was demonstrated as the capacity of polyphenols to transport zinc cations across the liposome membrane and increase the zinc-specific fluorescence of the encapsulated fluorophore FluoZin-3. In addition, the zinc chelation strength of the polyphenols was also tested in a competition assay based on the fluorescence quenching of zinc-dependent fluorescence emitted by zinc-FluoZin-3 complex. Finally, the correlation between the chelation capacity and ionophore activity is demonstrated, thus underlining the sequestering or ionophoric activity that the phenolic compounds can display, thus, providing better knowledge of the importance of the structural conformation versus their biological activity. Furthermore, the assays developed can be used as tools for rapid, high-throughput screening of families of polyphenols towards different biometals. PMID:26617034

  3. Effect of High-Intensity Focused Ultrasound on Drug Release from Doxorubicin-Loaded PEGylated Liposomes and Therapeutic Effect in Colorectal Cancer Murine Models.

    Science.gov (United States)

    Jeong, Hwan-Seok; Hwang, Hyosook; Oh, Phil-Sun; Kim, Eun-Mi; Lee, Tai Kyoung; Kim, Minjoo; Kim, Hyeon Soo; Lim, Seok Tae; Sohn, Myung-Hee; Jeong, Hwan-Jeong

    2016-04-01

    The goal of the study described here was to evaluate the use of high-intensity focused ultrasound (HIFU) in drug release and its application in cancer therapy. HIFU was set to minimize hyperthermia, particularly non-specific hyperthermia, of exposed areas. An in vitro temperature-sensitive hydrogel phantom model determined the parameters of HIFU under mild condition settings (spatial average temporal average intensity [ISATA] = 83.35 W/cm(2)). PEGylated liposomal indocyanine green (LCLP-ICG) and PEGylated liposomal doxorubicin (LCLP-Dox) were prepared with the same mole ratio to allow direct comparison of drug release in vitro and in vivo. We induced drug release with HIFU treatment using LCLP-ICG coupled with optical imaging in vitro and in vivo. The size distribution changes in LCLP-ICG in vitro and fluorescence intensity changes in ICG after intra-tumoral injection of LCLP-ICG into CT26 solid tumors in vivo followed by HIFU confirmed the feasibility of the system. We validated the therapeutic effect of HIFU treatment of the CT26 mouse tumor model. The tumor growth rate was significantly reduced (p HIFU treatment, and the chemotherapy of the CT26 solid tumors was found to be highly efficient. PMID:26795498

  4. Ion exchange behaviour of polymeric zirconium cations

    International Nuclear Information System (INIS)

    Polymeric zirconium cations formed in weakly acid solutions (pH2) are taken up strongly into macroporous cation exchange resins, while uptake into normal cation exchange resins (pore diameter about 1 nm) is low. Macroporous cation exchange resins loaded with polymeric Zr cations are shown to function as ligand exchange sorbents. (Authors)

  5. Effect of Lyophilization and Freeze-thawing on the Stability of siRNA-liposome Complexes

    OpenAIRE

    Yadava, Preeti; Gibbs, Melissa; de Castro, Carlos; Hughes, Jeffrey A.

    2007-01-01

    The purpose of this research was to describe the application of lyophilization in the delivery of siRNA using cationic lipids by addressing the long-term formulation/stability issues associated with cationic lipids and to understand the mechanism of lyoprotection. siRNA liposomes complexes were formed in different potential cyro/lyoprotectants and subjected to either lyophilization or freeze thaw cycles. siRNA, liposomes and/or lipoplexes were tested for activity, SYBR Green I binding, cellul...

  6. Liposomal formulations for inhalation.

    Science.gov (United States)

    Cipolla, David; Gonda, Igor; Chan, Hak-Kim

    2013-08-01

    No marketed inhaled products currently use sustained release formulations such as liposomes to enhance drug disposition in the lung, but that may soon change. This review focuses on the interaction between liposomal formulations and the inhalation technology used to deliver them as aerosols. There have been a number of dated reviews evaluating nebulization of liposomes. While the information they shared is still accurate, this paper incorporates data from more recent publications to review the factors that affect aerosol performance. Recent reviews have comprehensively covered the development of dry powder liposomes for aerosolization and only the key aspects of those technologies will be summarized. There are now at least two inhaled liposomal products in late-stage clinical development: ARIKACE(®) (Insmed, NJ, USA), a liposomal amikacin, and Pulmaquin™ (Aradigm Corp., CA, USA), a liposomal ciprofloxacin, both of which treat a variety of patient populations with lung infections. This review also highlights the safety of inhaled liposomes and summarizes the clinical experience with liposomal formulations for pulmonary application. PMID:23919478

  7. Significantly enhanced tumor cellular and lysosomal hydroxychloroquine delivery by smart liposomes for optimal autophagy inhibition and improved antitumor efficiency with liposomal doxorubicin.

    Science.gov (United States)

    Wang, Yang; Shi, Kairong; Zhang, Li; Hu, Guanlian; Wan, Jingyu; Tang, Jiajing; Yin, Sheng; Duan, Jiandong; Qin, Ming; Wang, Neng; Xie, Dandan; Gao, Xinle; Gao, Huile; Zhang, Zhirong; He, Qin

    2016-06-01

    Hydroxychloroquine (HCQ) inhibits autophagy and therefore can sensitize some cancer cells to chemotherapy, but the high doses required limit its clinical use. Here we show that loading HCQ into liposomes (HCQ/Lip) decorated with a pH-sensitive TH-RGD targeting peptide (HCQ/Lip-TR) can concentrate HCQ in B16F10 tumor cells and lysosomes. HCQ/Lip-TR was efficiently internalized as a result of its ability to bind ITGAV-ITGB3/integrin αvβ3 receptors highly expressed on the tumor cell surface and to undergo charge reversal from anionic at pH 7.4 to cationic at pH 6.5. Studies in vitro at pH 6.5 showed that the intracellular HCQ concentration was 35.68-fold higher, and lysosomal HCQ concentration 32.22-fold higher, after treating cultures with HCQ/Lip-TR than after treating them with free HCQ. The corresponding enhancements observed in mice bearing B16F10 tumors were 15.16-fold within tumor cells and 14.10-fold within lysosomes. HCQ/Lip-TR was associated with milder anemia and milder myosuppressive reductions in white blood cell and platelet counts than free HCQ, as well as less accumulation in the small intestine, which may reduce risk of intestinal side effects. In addition, co-delivering HCQ/Lip-TR with either free doxorubicin (DOX) or liposomal DOX improved the ability of DOX to inhibit tumor growth. Biochemical, electron microscopy and immunofluorescence experiments confirmed that HCQ/Lip-TR blocked autophagic flux in tumor cells. Our results suggest that loading HCQ into Lip-TR liposomes may increase the effective concentration of the inhibitor in tumor cells, allowing less toxic doses to be used. PMID:27123811

  8. pH-sensitive liposomes: acid-induced liposome fusion.

    OpenAIRE

    Connor, J.; Yatvin, M B; Huang, L.

    1984-01-01

    Sonicated unilamellar liposomes containing phosphatidylethanolamine and palmitoylhomocysteine fuse rapidly when the medium pH is lowered from 7 to 5. Liposome fusion was demonstrated by (i) mixing of the liposomal lipids as shown by resonance energy transfer, (ii) gel filtration, and (iii) electron microscopy. The pH-sensitive fusion of liposomes was observed only when palmitoylhomocysteine (greater than or equal to 20 mol%) was present in the liposomes. The presence of phosphatidyl-ethanolam...

  9. Liposomal cancer therapy: exploiting tumor characteristics

    DEFF Research Database (Denmark)

    Kaasgaard, Thomas; Andresen, Thomas Lars

    2010-01-01

    Importance of the field: More than 10 million people worldwide are diagnosed with cancer each year, and the development of effective cancer treatments is consequently of great significance. Cancer therapy is unfortunately hampered by severe dose-limiting side effects that reduce the efficacy of...... cancer treatments. In the search for more effective cancer treatments, nanoparticle- based drug delivery systems, such as liposomes, that are capable of delivering their drug payload selectively to cancer cells are among the most promising approaches. Areas covered in this review: This review provides 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...

  10. Preparation and anti-tumor activity of a novel liposome-loaded drug%RGD脂肪醇与17-AAG脂质体的制备及抗肿瘤活性研究

    Institute of Scientific and Technical Information of China (English)

    李雪梅; 王玉记; 吴建辉; 崔纯莹

    2015-01-01

    Objective To prepare an Arg-Gly-Asp-Phe-fatty alcohol ( RGDFOC12 ) liposomes-loaded 17-allylamino-17-demethoxygeldanamycin(17-AAG). Methods RGDFOC12 liposomes-loaded 17-AAG(RLAs) was prepared by film dispersion method and evaluated by particle size analysis, Zeta potential, encapsulation efficiency, the release in vitro, plasma stability, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide( MTT) assay and the anti-tumor activity in vivo. Results The RLAs was stable colloidal dispersion system in spherical shape of (130.6±0.6)nm in diameter and the Zeta potential was (-28.37±1.67)mV. The release of RLAs in vitro showed that the released percentage of RLAs in pH 5. 4 is more than that in pH 7. 4. The MTT assay proved that RLAs inhibited the proliferation of cancer cells. The anti-tumor assay showed that RLAs inhibited tumor growth and reduced the toxicity. Conclusion The RLAs were prepared by film dispersion method. RLAs showed anti-tumor activity in vivo and good potential in cancer therapy.%目的:制备一种新的精氨酸-甘氨酸-天冬氨酸-苯丙氨酸-脂肪醇( Arg-Gly-Asp-Phe-fatty alcohol,RGDFOC12)与17-丙烯氨基-17-去甲氧基格尔德霉素(17-allylamino-17-demethoxygeldanamycin,17-AAG)的脂质体(RGDFOC12 liposomes-loaded 17-AAG, RLAs)。方法采用薄膜分散-探头超声法制备;采用激光纳米粒度仪、透射电镜和扫描电镜测定粒径,Zeta电位和外观形态;采用动态透析法测定药物释放;采用四甲基偶氮唑盐[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,MTT]考察其对5种人肿瘤细胞株增生的抑制作用;通过瘤质量、存活数、体质量、脏器指数比评价其在小鼠体内抗肿瘤效果。结果制备得到的RLAs的粒径为(130.6±0.6)nm,Zeta电位为(-28.37±1.67)mV,外观形态为球形,包封率为80%以上。 RLAs在pH 5.4环境的累积释放百分数大于在pH 7.4环境的累积释放百分数。 RLAs在血浆中可稳定存在,12 h

  11. Pharmacokinetic, biodistribution and therapeutic efficacy of 5-fluorouracil-loaded pH-sensitive PEGylated liposomal nanoparticles in HCT-116 tumor bearing mouse

    Science.gov (United States)

    Udofot, Ofonime; Affram, Kevin; Smith, Taylor; Tshabe, Bulumko; Krishnan, Sunil; Sachdeva, Mandip; Agyare, Edward

    2016-01-01

    The objective of the study was to investigate the pharmacokinetics and efficacy of 5-FU entrapped pH-sensitive liposomal nanoparticles with surface-modified anti-epidermal growth factor receptor (EGFR) antibody (pHLNps-5-FU) delivery system. Cytotoxicity of 5-FU and pHLNps-5-FU was determined in vitro against HCT-116 cells. The biodistribution and pharmacokinetic parameters of the administered 5-FU and pHLNps-5-FU as well as efficacy of 5-FU and pHLNps-5-FU were determined in HCT-116 subcutaneous mouse model. Mean size of pHLNp-5-FU was 164.3 ± 8.4 nm with entrapment efficiency (E.E) of 54.17%. While cytotoxicity of 5-FU and pHLNps-5-FU showed a strong dose-dependent, pHLNps-5-FU proved to be more effective (2–3 fold high) than that of 5-FU against HCT-116 cells. Pharmacokinetic study showed a prolonged plasma circulation of pHLNps-5-FU and a more significant body exposure while accumulation of pHLNps-5-FU in tumor was significantly higher than that of free 5-FU. Further, the efficacy of pHLNps-5-FU, was greater than free 5-FU at equivalent 5-FU dose. The study suggests that pHLNps may be an effective drug delivery system to enhance the anticancer activity of 5-FU against colorectal tumor growth.

  12. Protein antigen adsorption to the DDA/TDB liposomal adjuvant

    DEFF Research Database (Denmark)

    Hamborg, Mette; Jorgensen, Lene; Bojsen, Anders Riber; Christensen, Dennis; Foged, Camilla

    2013-01-01

    Understanding the nature of adjuvant-antigen interactions is important for the future design of efficient and safe subunit vaccines, but remains an analytical challenge. We studied the interactions between three model protein antigens and the clinically tested cationic liposomal adjuvant composed...

  13. Liposomal nanoparticles as a drug delivery vehicle against osteosarcoma

    Science.gov (United States)

    Dhule, Santosh Subhashrao

    The delivery of curcumin, a broad-spectrum anticancer drug, has been explored in the form of liposomal nanoparticles to treat osteosarcoma (OS). Curcumin is water insoluble and an effective delivery route is through encapsulation in cyclodextrins followed by a second encapsulation in liposomes. Liposomal curcumin's potential was evaluated against cancer models of mesenchymal (OS) and epithelial origin (breast cancer). The resulting 2-Hydroxypropyl-gamma-cyclodextrin/curcumin - liposome complex shows promising anticancer potential both in vitro and in vivo against KHOS OS cell line and MCF-7 breast cancer cell line. An interesting aspect is that liposomal curcumin initiates the caspase cascade that leads to apoptotic cell death in vitro in comparison with DMSO-curcumin induced autophagic cell death. In addition, the efficiency of the liposomal curcumin formulation was confirmed in vivo using a xenograft OS model. Curcumin-loaded gamma-cyclodextrin liposomes indicate significant potential as delivery vehicles for the treatment of cancers of different tissue origin. The second part of this study examines the anti-tumor potential of curcumin and C6 ceramide (C6) against osteosarcoma cell lines when both are encapsulated in the bilayer of liposomal nanoparticles. Curcumin in combination with C6 showed 1.5 times enhanced cytotoxic effect in the case of MG-63 and KHOS OS cell lines, in comparison with systems with curcumin alone. Interestingly, C6-curcumin liposomes were found to be less toxic on untransformed human cells in comparison to OS cell lines. In addition, cell cycle assays on a KHOS cell line after treatment revealed that curcumin only liposomes induced G 2/M arrest by upregulation of cyclin B1, while C6 only liposomes induced G1 arrest by downregulation of cyclin D1. C6-curcumin liposomes induced G2/M arrest and showed a combined effect in the expression levels of cyclin D1 and cyclin B1. Using pegylated liposomes to increase the plasma half-life and tagging

  14. Liposome-encapsulated polyethylenimine/oligonucleotide polyplexes prepared by reverse-phase evaporation technique.

    Science.gov (United States)

    Ko, Young Tag; Bickel, Ulrich

    2012-06-01

    Liposome-encapsulated polyplex system represents a promising delivery system for oligonucleotide-based therapeutics such as siRNA and asODN. Here, we report a novel method to prepare liposome-encapsulated cationic polymer/oligonucleotide polyplexes based on the reverse-phase evaporation following organic extraction of the polyplexes. The polyplexes of polyethylenimine and oligonucleotide were first formed in aqueous buffer at an N/P ratio of 6. The overall positively charged polyplexes were then mixed with the anionic phospholipids in overall organic media. The overall organic environment and electrostatic interaction between anionic phospholipids and positively charged polyplexes resulted in inverted micelle-like particles with the polyplexes in the core. After phase separation, the hydrophobic particles were recovered in organic phase. Reverse-phase evaporation of the organic solvent in the presence of hydrophilic polymer-grafted lipids resulted in a stable aqueous dispersion of hydrophilic lipid-coated particles with the polyplex in the core. Transmission electron microscopy visualization revealed spherical structures with heavily stained polyplex cores surrounded by lightly stained lipid coats. The lipid-coated polyplex particles showed colloidal stability, complete protection of the loaded oligonucleotide molecules from enzymatic degradation, and high loading efficiency of more than 80%. Thus, this technique represents an alternative method to prepare lipid-coated polyplex particles as a delivery system of oligonucleotide therapeutics. PMID:22328240

  15. Preparation of novel capsosome with liposomal core by layer-by-Layer self-assembly of sodium hyaluronate and chitosan.

    Science.gov (United States)

    Yoo, Cha Young; Seong, Joon Seob; Park, Soo Nam

    2016-08-01

    Multi-compartmentalized capsosomes are polyelectrolyte capsules with liposomes as cargo, and are prepared by combining liposomes and polymer capsules. They offer additional functionality while maintaining the advantages and compensating for the weak points of both systems. In this study, a polyelectrolyte multilayered liposome was prepared by alternating adsorption of negatively charged sodium hyaluronate (HA) and positively charged chitosan (CH) on the surface of a cationic core liposome (CL) via layer-by-layer (LbL) deposition. Then, smaller sized liposomes (L) were coated onto the multilayered liposome. Lastly, the particle surfaces were coated with HA as a capping layer to obtain a novel type of capsosome with a liposomal core. The amount of adsorbed liposome was measured for different pH values (pH 2-10) and with liposome solutions of different concentrations (1-3%). The highest liposome adsorption occurred at pH 10 in the 3% solution, respectively. Finally, capsosomes in the size range of 500nm to 2μm were observed and the attached liposomes were located both on the surface and within the polymer shell. In conclusion, the cell-mimicking, liposome-based capsosomes could have infinite applications in the field of medicine, pharmaceuticals, and cosmetics as compartmentalized microreactors, multi-drug delivery systems with controlled release, or functional artificial cells in the future. PMID:27085041

  16. Actinide cation-cation complexes

    International Nuclear Information System (INIS)

    The +5 oxidation state of U, Np, Pu, and Am is a linear dioxo cation (AnO2+) with a formal charge of +1. These cations form complexes with a variety of other cations, including actinide cations. Other oxidation states of actinides do not form these cation-cation complexes with any cation other than AnO2+; therefore, cation-cation complexes indicate something unique about AnO2+ cations compared to actinide cations in general. The first cation-cation complex, NpO2+·UO22+, was reported by Sullivan, Hindman, and Zielen in 1961. Of the four actinides that form AnO2+ species, the cation-cation complexes of NpO2+ have been studied most extensively while the other actinides have not. The only PuO2+ cation-cation complexes that have been studied are with Fe3+ and Cr3+ and neither one has had its equilibrium constant measured. Actinides have small molar absorptivities and cation-cation complexes have small equilibrium constants; therefore, to overcome these obstacles a sensitive technique is required. Spectroscopic techniques are used most often to study cation-cation complexes. Laser-Induced Photacoustic Spectroscopy equilibrium constants for the complexes NpO2+·UO22+, NpO2+·Th4+, PuO2+·UO22+, and PuO2+·Th4+ at an ionic strength of 6 M using LIPAS are 2.4 ± 0.2, 1.8 ± 0.9, 2.2 ± 1.5, and ∼0.8 M-1

  17. Antigen-specific suppression of inflammatory arthritis using liposomes.

    Science.gov (United States)

    Capini, Christelle; Jaturanpinyo, Montree; Chang, Hsin-I; Mutalik, Srinivas; McNally, Alice; Street, Shayna; Steptoe, Raymond; O'Sullivan, Brendan; Davies, Nigel; Thomas, Ranjeny

    2009-03-15

    Existing therapies for rheumatoid arthritis and other autoimmune diseases are not Ag specific, which increases the likelihood of systemic toxicity. We show that egg phosphatidylcholine liposomes loaded with Ag (OVA or methylated BSA) and a lipophilic NF-kappaB inhibitor (curcumin, quercetin, or Bay11-7082) suppress preexisting immune responses in an Ag-specific manner. We injected loaded liposomes into mice primed with Ag or into mice suffering from Ag-induced inflammatory arthritis. The liposomes targeted APCs in situ, suppressing the cells' responsiveness to NF-kappaB and inducing Ag-specific FoxP3(+) regulatory T cells. This regulatory mechanism suppressed effector T cell responses and the clinical signs of full-blown Ag-induced arthritis. Thus, liposomes encapsulate Ags and NF-kappaB inhibitors stably and efficiently and could be readily adapted to deliver Ags and inhibitors for Ag-specific suppression of other autoimmune and allergic diseases. PMID:19265134

  18. Targeted liposomal drug delivery to monocytes and macrophages.

    OpenAIRE

    Ciara Kelly; Caroline Jefferies; Sally-Ann Cryan

    2011-01-01

    As the role of monocytes and macrophages in a range of diseases is better understood, strategies to target these cell types are of growing importance both scientifically and therapeutically. As particulate carriers, liposomes naturally target cells of the mononuclear phagocytic system (MPS), particularly macrophages. Loading drugs into liposomes can therefore offer an efficient means of drug targeting to MPS cells. Physicochemical properties including size, charge and lipid composition can ha...

  19. Improved Delivery of Caffeic Acid through Liposomal Encapsulation

    OpenAIRE

    Katuwavila, Nuwanthi P.; A. D. L. Chandani Perera; V. Karunaratne; Gehan A. J. Amaratunga; D. Nedra Karunaratne

    2016-01-01

    Photoageing resulting from long term exposure of the skin to UV light can be minimized by scavenging the reactive photochemical intermediates with antioxidants. For effective photoprotection, the antioxidant must overcome the barrier properties of the skin and reach the target site in significant amounts. The present study aims to improve the skin penetration of caffeic acid, a very effective free radical scavenger, by encapsulating in liposomes. Caffeic acid loaded liposomes prepared using t...

  20. Liposome production by microfluidics: potential and limiting factors

    OpenAIRE

    Dario Carugo; Elisabetta Bottaro; Joshua Owen; Eleanor Stride; Claudio Nastruzzi

    2016-01-01

    This paper provides an analysis of microfluidic techniques for the production of nanoscale lipid-based vesicular systems. In particular we focus on the key issues associated with the microfluidic production of liposomes. These include, but are not limited to, the role of lipid formulation, lipid concentration, residual amount of solvent, production method (including microchannel architecture), and drug loading in determining liposome characteristics. Furthermore, we propose microfluidic archi...

  1. Anti-inflammatory activity of cationic lipids.

    Science.gov (United States)

    Filion, M C; Phillips, N C

    1997-10-01

    1. The effect of liposome phospholipid composition has been assumed to be relatively unimportant because of the presumed inert nature of phospholipids. 2. We have previously shown that cationic liposome formulations used for gene therapy inhibit, through their cationic component, the synthesis by activated macrophages of the pro-inflammatory mediators nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha). 3. In this study, we have evaluated the ability of different cationic lipids to reduce footpad inflammation induced by carrageenan and by sheep red blood cell challenge. 4. Parenteral (i.p. or s.c) or local injection of the positively charged lipids dimethyldioctadecylammomium bromide (DDAB), dioleyoltrimethylammonium propane (DOTAP), dimyristoyltrimethylammonium propane (DMTAP) or dimethylaminoethanecarbamoyl cholesterol (DC-Chol) significantly reduced the inflammation observed in both models in a dose-dependent manner (maximum inhibition: 70-95%). 5. Cationic lipids associated with dioleyol- or dipalmitoyl-phosphatidylethanolamine retained their anti-inflammatory activity while cationic lipids associated with dipalmitoylphosphatidylcholine (DPPC) or dimyristoylphosphatidylglycerol (DMPG) showed no anti-inflammatory activity, indicating that the release of cationic lipids into the macrophage cytoplasm is a necessary step for anti-inflammatory activity. The anti-inflammatory activity of cationic lipids was abrogated by the addition of dipalmitoylphosphatidylethanolamine-poly(ethylene)glycol-2000 (DPPE-PEG2000) which blocks the interaction of cationic lipids with macrophages. 6. Because of the significant role of protein kinase C (PKC) in the inflammatory process we have determined whether the cationic lipids used in this study inhibit PKC activity. The cationic lipids significantly inhibited the activity of PKC but not the activity of a non-related protein kinase, PKA. The synthesis of interleukin-6 (IL-6), which is not dependent on PKC activity for its

  2. Tuftsin-bearing liposomes as rifampin vehicles in treatment of tuberculosis in mice.

    OpenAIRE

    Agarwal, A.; Kandpal, H; Gupta, H. P.; N. B. Singh; Gupta, C M

    1994-01-01

    The antitubercular activity of rifampin was considerably increased when it was encapsulated in egg phosphatidylcholine liposomes. A further increase in the activity was observed when the macrophage activator tetrapeptide tuftsin was grafted on the surface of the drug-loaded liposomes. Intermittent treatments (twice weekly) with these preparations were significantly more effective than the continuous treatments. Rifampin delivered twice weekly for 2 weeks in tuftsin-bearing liposomes was at le...

  3. 硫酸长春新碱脂质体的质量评价研究%Quality evaluation of Vincristine Sulphate Liposomes

    Institute of Scientific and Technical Information of China (English)

    张雪冰; 李文静; 王杏林; 杨志强; 吴溪

    2015-01-01

    Objective To evaluate the quality of Vincristine Sulphate Liposome.Methods Vincristine sulphate was encapsulated in the liposomes using the pH gradient-dependent remote loading technique. The morphological examination of liposomes was observed with transmission electron microscopy. The encapsulation efficiency was determined by cation exchange resin column. Their pH value, particle size, Zeta potential, stability, andin vitrodeliveryof vincristine sulphate were investigated.Results The morphology of Vincristine Sulphate Liposome showed that liposomes were uniformity, good roundness. The particle size of the liposomes was about 120 nm, the Zeta potential was about 10 mV, and the encapsulation efficiency was above 90%. Vincristine sulphate liposomes did not occur significant changes under the light condition and at 4℃, 18℃, and 25℃ conditions. At 40℃, the encapsulation efficiency decreased.Conclusion The method is accurate and simple to evaluate the quality of Vincristine Sulphate Liposomes.%目的:评价硫酸长春新碱脂质体的质量。方法采用pH梯度法制备硫酸长春新碱脂质体。透射电镜观察脂质体的外观形态,阳离子交换树脂柱法测定包封率,并考察其pH值、粒径、Zeta电位、稳定性及体外释放规律。结果形态学观察结果显示,脂质体均匀圆整度良好。硫酸长春新碱脂质体粒径为120 nm左右,Zeta电位约为10 mV,包封率均在90%以上。光照、4℃、18℃、25℃条件下,脂质体各项指标无显著变化。40℃条件下,包封率明显降低。结论本法准确,操作简便,可用于硫酸长春新碱脂质体的质量评价。

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

    Energy Technology Data Exchange (ETDEWEB)

    Inoh, Yoshikazu; Furuno, Tadahide [School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650 (Japan); Hirashima, Naohide [Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603 (Japan); Kitamoto, Dai [National Institute of Advanced Industrial Science and Technology (AIST), Central 5, 1-1 Higashi, Tsukuba 305-8565 (Japan); Nakanishi, Mamoru, E-mail: mamoru@dpc.agu.ac.jp [School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650 (Japan)

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer We use MEL-A-containing cationic liposomes for siRNA delivery. Black-Right-Pointing-Pointer MEL-A-containing cationic liposomes can efficiently and rapidly deliver siRNA into the cytoplasm. Black-Right-Pointing-Pointer 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 Trade-Mark-Sign 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

  5. 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. PMID:22001930

  6. Liposomal SLA co-incorporated with PO CpG ODNs or PS CpG ODNs induce the same protection against the murine model of leishmaniasis.

    Science.gov (United States)

    Shargh, Vahid Heravi; Jaafari, Mahmoud Reza; Khamesipour, Ali; Jaafari, Iman; Jalali, Seyed Amir; Abbasi, Azam; Badiee, Ali

    2012-06-01

    First generation Leishmania vaccines consisting of whole killed parasites with or without adjuvants have reached phase 3 trial and failed to show enough efficacy mainly due to the lack of an appropriate adjuvant. In this study, the nuclease-resistant phosphorothioate CpG oligodeoxynucleotides (PS CpG) or nuclease-sensitive phosphodiester CpG ODNs (PO CpG) were used as adjuvants to enhance immunogenicity and rate of protection against leishmaniasis. Due to the susceptibility of PO CpG to nuclease degradation, an efficient liposomal delivery system was developed to protect them from degradation. 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP) as a cationic lipid was used because of its unique adjuvanticity and electrostatic interaction with negatively charged CpG ODNs. To evaluate the role of liposomal formulation in protection rate and enhanced immune response, BALB/c mice were immunized subcutaneously with liposomal soluble Leishmania antigens (SLA) co-incorporated with PO CpG (Lip-SLA-PO CpG), Lip-SLA-PS CpG, SLA+PO CpG, SLA+PS CpG, SLA or buffer. As criteria for protection, footpad swelling at the site of challenge, parasite loads, the levels of IFN-γ and IL-4, and the IgG subtypes were evaluated. The groups of mice receiving Lip-SLA-PO CpG or Lip-SLA-PS CpG showed a high protection rate compared with the control groups. In addition, there was no significant difference in immune response generation between mice immunized with PS CpG and the group receiving PO CpG when incorporated into the liposomes. The results suggested that liposomal form of PO CpG might be used instead of PS CpG in future vaccine formulations as an efficient adjuvant. PMID:22465747

  7. LIPOSOMES: AN OVERVIEW

    Directory of Open Access Journals (Sweden)

    Sipai Altaf Bhai. M

    2012-02-01

    Full Text Available Drug development technologies constituting innovations at the formulation end in the Pharmaceutical industry has received a lot of attention in past two decades. Drug delivery as an opportunity to extend product life cycles has indeed proved its place in the market with significant advantages of therapeutic gains as well as commercial success. Carrier technology offers an intelligent approach for drug delivery by coupling the drug to a carrier particle such as liposomes, microspheres, nanoparticles, etc. which modulates the release and absorption characteristics of the drug. Liposomes are well known to alter the bio distribution of entrapped substances by protecting the enclosed material. They are widely used as vehicles to target the specific molecule to specific organ. During the last few decades liposomes have attracted great interest as ideal models for biological membranes as well as efficient carriers for drugs, diagnostics, vaccines, nutrients and other bioactive agents. Many techniques and methodologies have involved for the manufacture of liposomes, on small and large scales, since their introduction to the scientific community around 40 years ago. This article intends to provide an overview of the advantages and disadvantages of liposome preparation methods,their stability, bio distribution and their uses as drug delivery systems. The conventional method of preparing liposomes is basically for the multilamellar vesicles (MLVs. However, other methods are used to reduce the size of these MLVs to small unilamellar vesicles (SUVs so as to increase their plasma lifetime and consequently increase the possibility of achieving greater tissue localisation. Some of these methods of size reduction are sonication and high pressure extrusion. Each of these methods has its own advantages and disadvantages. Large unilamellar vesicles (LUVs, on the other hand, are prepared mainly by detergent removal method and reverse phase extrusion technique. There

  8. Polymer Chemistry and Liposome Technology

    OpenAIRE

    Tirrell, David A.

    1988-01-01

    Polymer chemistry has a great deal to offer in the construction of synthetic liposomal membranes for use in biology and medicine. This chapter explores the preparation and properties of polymeric liposomes , with particular emphasis on the use of controlled polyelectrolyte adsorption to manipulate liposomal membrane properties.

  9. Preparation of protamine cationic nanobubbles and experimental study of their physical properties and in vivo contrast enhancement.

    Science.gov (United States)

    Tong, Hai-Peng; Wang, Luo-Fu; Guo, Yan-Li; Li, Lang; Fan, Xiao-Zhou; Ding, Jun; Huang, Hai-Yun

    2013-11-01

    In this study, we aimed to prepare a novel type of microbubble (MB), protamine cationic nanobubble (NB), to provide a new vector for tumor gene therapy. We prepared cationic NBs with protamine and other lipid components using mechanical oscillation. The protamine cationic NBs had a mean diameter of 521.2 ± 37.57 nm, a zeta potential of +18.5 mV, and a gene-carrying capacity of 15.69 μg androgen receptor (AR) siRNA per 10(8) NBs. The cationic NBs exhibited superior contrast enhancement for in vivo imaging compared with SonoVue (Bracco, Geneva, Switzerland), and their physical properties did not change significantly after 1 wk; meanwhile, the transfection efficiency of the cationic NBs in androgen-independent prostate cancer cells mediated by ultrasound irradiation was better than that of liposomes (82.17 ± 7.4% vs. 55.04 ± 5.4%, p < 0.01). Therefore, the protamine cationic NB can be considered for use as a novel type of gene-loading MB for ultrasound imaging and MB-mediated gene therapy of tumors. PMID:23932278

  10. Liposomal delivery of radionuclides for cancer diagnostics and radiotherapy

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa

    loading experiments and isothermal titration calorimetry (ITC) measurements. Various chelators, ionophores and lipophilic chelators were tested at different pH and temperature conditions. Liposomes passively accumulate in tumors due to the enhanced permeability and retention (EPR) effect. In Article I...... of PEGylated 64Cu-liposomes with and without TATE, and their ability to image NE tumors in tumor-bearing mice using PET. Further, we compare the liposome tumor accumulation and imaging capability with that of the radiolabeled somatostatin analog 64Cu-DOTA-TATE. During the past 30 years, ionophores......, a so called “unassisted” loading, excluding any use of ionophores and lipophilic chelators. Project IV presents results from this invention (Patent II), where a presentation of various parameters affecting the efficiency of the unassisted loading method is given. Section 5 summarizes the regulatory...

  11. On the phase diagram of reentrant condensation in polyelectrolyte-liposome complexation

    Science.gov (United States)

    Sennato, S.; Bordi, F.; Cametti, C.

    2004-09-01

    Complexation of polyions with oppositely charged spherical liposomes has been investigated by means of dynamic light scattering measurements and a well-defined reentrant condensation has been observed. The phase diagram of charge inversion, recently derived [T. T. Nguyen and B. I. Shklovskii, J. Chem. Phys. 115, 7298 (2001)] for the complexation of DNA with charged spherical macroions, has been employed in order to define the boundaries of the region where polyion-liposome complexes begin to condense, forming larger aggregates, and where aggregates dissolve again, towards isolated polyion-coated-liposome complexes. A reasonable good agreement is observed in the case of complexes formed by negatively charged polyacrylate sodium salt polyions and liposomes built up by cationic lipids (dioleoyltrimethylammoniumpropane), in an extended liposome concentration range.

  12. Liposomal encapsulation of dexamethasone modulates cytotoxicity, inflammatory cytokine response, and migratory properties of primary human macrophages

    NARCIS (Netherlands)

    Bartneck, M.; Peters, F.M.; Warzecha, K.T.; Bienert, M.; Bloois, van L.; Trautwein, C.; Lammers, T.G.G.M.; Tacke, F.

    2014-01-01

    The encapsulation of drugs into liposomes aims to enhance their efficacy and reduce their toxicity. Corticosteroid-loaded liposomes are currently being evaluated in patients suffering from rheumatoid arthritis, atherosclerosis, colitis, and cancer. Here, using several different fluorophore-labeled f

  13. Glycosaminoglycan-Mediated Selective Changes in the Aggregation States, Zeta Potentials, and Intrinsic Stability of Liposomes

    OpenAIRE

    Nyren-Erickson, Erin K; Haldar, Manas K.; Totzauer, Jessica R.; Ceglowski, Riley; Patel, Dilipkumar S.; Daniel L. Friesner; Srivastava, D. K.; Mallik, Sanku

    2012-01-01

    Though the aggregation of glycosaminoglycans (GAGs) in the presence of liposomes and divalent cations has been previously reported, the effect of different GAG species, as well as minor changes in GAG composition on the aggregates formed is yet unknown. If minor changes in GAG composition produce observable changes in liposome aggregate diameter or zeta potential, such a phenomenon may be used to detect potentially dangerous over-sulfated contaminants in heparin. We studied the mechanism of t...

  14. Intranasal delivery of cationic PLGA nano/microparticles-loaded FMDV DNA vaccine encoding IL-6 elicited protective immunity against FMDV challenge.

    Directory of Open Access Journals (Sweden)

    Gang Wang

    Full Text Available Mucosal vaccination has been demonstrated to be an effective means of eliciting protective immunity against aerosol infections of foot and mouth disease virus (FMDV and various approaches have been used to improve mucosal response to this pathogen. In this study, cationic PLGA (poly(lactide-co-glycolide nano/microparticles were used as an intranasal delivery vehicle as a means administering FMDV DNA vaccine encoding the FMDV capsid protein and the bovine IL-6 gene as a means of enhancing mucosal and systemic immune responses in animals. Three eukaryotic expression plasmids with or without bovine IL-6 gene (pc-P12A3C, pc-IL2AP12A3C and pc-P12AIL3C were generated. The two latter plasmids were designed with the IL-6 gene located either before or between the P12A and 3C genes, respectively, as a means of determining if the location of the IL-6 gene affected capsid assembly and the subsequent immune response. Guinea pigs and rats were intranasally vaccinated with the respective chitosan-coated PLGA nano/microparticles-loaded FMDV DNA vaccine formulations. Animals immunized with pc-P12AIL3C (followed by animals vaccinated with pc-P12A3C and pc-IL2AP12A3C developed the highest levels of antigen-specific serum IgG and IgA antibody responses and the highest levels of sIgA (secretory IgA present in mucosal tissues. However, the highest levels of neutralizing antibodies were generated in pc-IL2AP12A3C-immunized animals (followed by pc-P12AIL3C- and then in pc-P12A3C-immunized animals. pc-IL2AP12A3C-immunized animals also developed stronger cell mediated immune responses (followed by pc-P12AIL3C- and pc-P12A3C-immunized animals as evidenced by antigen-specific T-cell proliferation and expression levels of IFN-γ by both CD4+ and CD8+ splenic T cells. The percentage of animals protected against FMDV challenge following immunizations with pc-IL2AP12A3C, pc-P12AIL3C or pc-P12A3C were 3/5, 1/5 and 0/5, respectively. These data suggested that intranasal delivery

  15. Luteinizing hormone-releasing hormone receptor-mediated delivery of mitoxantrone using LHRH analogs modified with PEGylated liposomes

    Directory of Open Access Journals (Sweden)

    Yingna He

    2010-09-01

    Full Text Available Yingna He, Linhua Zhang, Cunxian SongKey Laboratory of Biomedical Material of Tianjin, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, ChinaAbstract: A sterically stabilized, mitoxantrone-loaded liposome, tailored to target luteinizing hormone-releasing hormone (LHRH receptor overexpressing cells, was developed to promote the efficiency of intracellular delivery of mitoxantrone through receptor-mediated endocytosis. Liposomes were prepared by lipid film hydration and an ultrasound dispersion process. Thiolated gonadorelin with affinity for the LHRH receptor was chemically coupled to N-[(3-maleimide-1-oxopropyl aminopropyl polyethylene glycol-carbamyl] distearoyl-l-phosphatidyl-ethanolamine via a thioether bond and subsequently inserted into polyethylene glycol-grafted liposomes. The liposome was characterized in terms of its size, ligand density, drug loading, and leakage properties. The targeting nature and antitumor effects of the liposomes were evaluated in vitro using cultured MCF-7 breast cancer cells. A protein assay of ligand coupling to the liposomal surface indicated that more than 60% of the LHRH peptides were inserted into the liposome bilayer. Up to 1.0 mg/mL of stable liposomal mitoxantrone loading was achieved, with approximately 98% of this being entrapped within the liposomes. In vitro cell culture studies revealed that the gonadorelin-modified liposomes bound to their target cells had significantly higher affinity and better antitumor efficiency than generic drug-loaded liposomes. These events were presumed to occur through specific interactions of the LHRH with its cognate receptors on the cell surface. It was concluded that the targeting properties of the delivery system would potentially improve the therapeutic benefits of mitoxantrone, as compared with nontargeted liposomes.Keywords: mitoxantrone, liposome, luteinizing hormone-releasing hormone receptor

  16. 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

    amount of negative charges in fluid liposomes reduces fluid liposomes-bacteria fusion when tested without calcium cations due to electric repulsion, but addition of calcium cations brings the fusion level of fluid liposomes to similar or higher levels. Among the negative phospholipids examined, DMPA gave the highest degree of fusion, DMPS and DMPG had intermediate fusion levels, and PI resulted in the lowest degree of fusion. Furthermore, the fluid liposomal encapsulated tobramycin was prepared, and the bactericidal effect occurred more quickly when bacteria were cultured with liposomal encapsulated tobramycin. Conclusion: The bactericidal potency of fluid liposomes is dramatically enhanced with respect to fusion ability when the fusogenic lipid, DOPE, is included. Regardless of changes in liposome composition, fluid liposomes-bacterium fusion is universally enhanced by calcium ions. The information obtained in this study will increase our understanding of fluid liposomal action mechanisms, and help in optimizing the new generation of fluid liposomal formulations for the treatment of pulmonary bacterial infections. Keywords: liposomes, fusion, bacteria, Pseudomonas aeruginosa, lipid composition

  17. Phototriggerable Liposomes: Current Research and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Anu Puri

    2013-12-01

    Full Text Available The field of cancer nanomedicine is considered a promising area for improved delivery of bioactive molecules including drugs, pharmaceutical agents and nucleic acids. Among these, drug delivery technology has made discernible progress in recent years and the areas that warrant further focus and consideration towards technological developments have also been recognized. Development of viable methods for on-demand spatial and temporal release of entrapped drugs from the nanocarriers is an arena that is likely to enhance the clinical suitability of drug-loaded nanocarriers. One such approach, which utilizes light as the external stimulus to disrupt and/or destabilize drug-loaded nanoparticles, will be the discussion platform of this article. Although several phototriggerable nanocarriers are currently under development, I will limit this review to the phototriggerable liposomes that have demonstrated promise in the cell culture systems at least (but not the last. The topics covered in this review include (i a brief summary of various phototriggerable nanocarriers; (ii an overview of the application of liposomes to deliver payload of photosensitizers and associated technologies; (iii the design considerations of photoactivable lipid molecules and the chemical considerations and mechanisms of phototriggering of liposomal lipids; (iv limitations and future directions for in vivo, clinically viable triggered drug delivery approaches and potential novel photoactivation strategies will be discussed.

  18. Molecular targeting of liposomal nanoparticles to tumor microenvironment

    Directory of Open Access Journals (Sweden)

    Zhao G

    2012-12-01

    Full Text Available Gang Zhao,1,2 B Leticia Rodriguez21Institute of Materia Medica, Shandong Academy of Medical Science, Shandong, China; 2Pharmaceutics Division, College of Pharmacy, The University of Texas at Austin, Austin, TX, USAAbstract: Liposomes are biodegradable and can be used to deliver drugs at a much higher concentration in tumor tissues than in normal tissues. Both passive and active drug delivery by liposomal nanoparticles can significantly reduce the toxic side effects of anticancer drugs and enhance the therapeutic efficacy of the drugs delivered. Active liposomal targeting to tumors is achieved by recognizing specific tumor receptors through tumor-specific ligands or antibodies coupled onto the surface of the liposomes, or by stimulus-sensitive drug carriers such as acid-triggered release or enzyme-triggered drug release. Tumors are often composed of tumor cells and nontumor cells, which include endothelial cells, pericytes, fibroblasts, stromal, mesenchymal cells, innate, and adaptive immune cells. These nontumor cells thus form the tumor microenvironment, which could be targeted and modified so that it is unfavorable for tumor cells to grow. In this review, we briefly summarized articles that had taken advantage of liposomal nanoparticles as a carrier to deliver anticancer drugs to the tumor microenvironment, and how they overcame obstacles such as nonspecific uptake, interaction with components in blood, and toxicity. Special attention is devoted to the liposomal targeting of anticancer drugs to the endothelium of tumor neovasculature, tumor associated macrophages, fibroblasts, and pericytes within the tumor microenvironment.Keywords: tumor microenvironment, endothelium, neovasculature, tumor-associated macrophages, cationic liposomes, ligand- or antibody-mediated targeting

  19. Enhanced transfection of tumor cells in vivo using “Smart” pH-sensitive TAT-modified pegylated liposomes

    OpenAIRE

    Kale, Amit A.; Torchilin, Vladimir P.

    2007-01-01

    Liposomes have been prepared loaded with DNA (plasmid encoding for the green fluorescent protein, GFP) and additionally modified with TATp and PEG, with PEG being attached to the liposome surface via both pH-sensitive hydrazone and non-pH-sensitive bonds. The pGFP-loaded liposomal preparations have been administered intratumorarly in tumor-bearing mice and the efficacy of tumor cell transfection was followed after 72 h. The administration of pGFP–TATp–liposomes with non-pH-sensitive PEG coati...

  20. Efficient intracellular drug-targeting of macrophages using stealth liposomes directed to the hemoglobin scavenger receptor CD163

    DEFF Research Database (Denmark)

    Etzerodt, Anders; Maniecki, Maciej Bogdan; Graversen, Jonas Heilskov;

    2012-01-01

    The hemoglobin scavenger receptor CD163 is exclusively expressed in the monocytic lineage and preferentially in tissue resident macrophages of the M2 phenotype and in macrophages in sites of inflammation and tumor growth. In the present study we have designed liposomes specifically targeting CD163...... by hydrophobic linkage of CD163-binding monoclonal antibodies to polyethylene glycol-coated liposomes ('stealth liposomes'). Targeting to the endocytic CD163 protein greatly increased the uptake of liposomes in CD163 transfected cells and macrophages as visualized by confocal microscopy and flow...... cytometry of cells exposed to CD163 targeting liposomes loaded with calcein. Strong cytotoxic effects were seen in CD163-expressing human monocytes by using the chemotherapeutic agent doxorubicin as cargo of the liposomes. In conclusion, the use of stealth liposomes modified to recognize CD163 is a...

  1. Silicone-stabilized liposomes as a possible novel nanostructural drug carrier.

    Science.gov (United States)

    Lewandowska-Łańcucka, Joanna; Mystek, Katarzyna; Gilarska, Adriana; Kamiński, Kamil; Romek, Marek; Sulikowski, Bogdan; Nowakowska, Maria

    2016-07-01

    Development of silicone stabilized liposomes which can serve as novel drug nanocarriers is presented. Silicone precursor 1,3,5,7-tetramethylcyclotetrasiloxane (D4(H)) was introduced into the bilayer of the cationic liposomes prepared from egg yolk phosphatidylocholine (PC) and double-tailed dimethyldioctadecylammonium bromide (DODAB). The silicone material was created inside of the liposomal bilayer in the base-catalyzed polycondensation process of the D4(H) what was confirmed employing (29)Si solid-state MAS NMR and FTIR measurements. Surfactant lysis experiments revealed that resulted systems can be effectively stabilized. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) measurements demonstrated that the silicone-stabilized liposomes have typical lipid vesicle's morphology and mean hydrodynamic diameters in the range of about 110nm. They have considerably lower tendency for aggregation than the pristine liposomes. The permeability of vesicles can be tuned by introducing various amounts of silicone precursor into the liposome bilayer, as confirmed in calcein-release studies. The effect of fetal bovine serum (FBS) on the stability of liposomes was also tested in in vitro studies. Biological studies revealed that resulted liposomes can be considered as possible drug nanocarriers because they are not toxic to human skin fibroblasts (HSFs) and mouse embryonic fibroblasts (MEFs). PMID:27022877

  2. The surface charge of liposomal adjuvants is decisive for their interactions with the Calu-3 and A549 airway epithelial cell culture models

    DEFF Research Database (Denmark)

    Ingvarsson, Pall Thor; Rasmussen, Ida Svahn; Viaene, Michelle; Irlik, Przemyslaw Jedrzej; Nielsen, Hanne Mørck; Foged, Camilla

    2014-01-01

    potential for mucosal vaccination via the airways. The purpose of this study was to investigate the importance of the liposomal surface charge on the interaction with lung epithelial cells. Thus, the cationic DDA in the liposomes was subjected to a step-wise replacement with the zwitterionic...

  3. Development of a liposomal nanodelivery system for nevirapine

    Directory of Open Access Journals (Sweden)

    Krishnan Uma M

    2010-07-01

    Full Text Available Abstract Background The treatment of AIDS remains a serious challenge owing to high genetic variation of Human Immunodeficiency Virus type 1 (HIV-1. The use of different antiretroviral drugs (ARV is significantly limited by severe side-effects that further compromise the quality of life of the AIDS patient. In the present study, we have evaluated a liposome system for the delivery of nevirapine, a hydrophobic non-nucleoside reverse transcriptase inhibitor. Liposomes were prepared from egg phospholipids using thin film hydration. The parameters of the process were optimized to obtain spherical liposomes below 200 nm with a narrow polydispersity. The encapsulation efficiency of the liposomes was optimized at different ratios of egg phospholipid to cholesterol as well as drug to total lipid. The data demonstrate that encapsulation efficiency of 78.14% and 76.25% were obtained at egg phospholipid to cholesterol ratio of 9:1 and drug to lipid ratio of 1:5, respectively. We further observed that the size of the liposomes and the encapsulation efficiency of the drug increased concomitantly with the increasing ratio of drug and lipid and that maximum stability was observed at the physiological pH. Thermal analysis of the drug encapsulated liposomes indicated the formation of a homogenous drug-lipid system. The magnitude of drug release from the liposomes was examined under different experimental conditions including in phosphate buffered saline (PBS, Dulbecco's Modified Eagle's Medium (DMEM supplemented with 10% fetal bovine serum or in the presence of an external stimulus such as low frequency ultrasound. Within the first 20 minutes 40, 60 and 100% of the drug was released when placed in PBS, DMEM or when ultrasound was applied, respectively. We propose that nevirapine-loaded liposomal formulations reported here could improve targeted delivery of the anti-retroviral drugs to select compartments and cells and alleviate systemic toxic side effects as a

  4. Cholesterol derived cationic lipids as potential non-viral gene delivery vectors and their serum compatibility.

    Science.gov (United States)

    Ju, Jia; Huan, Meng-Lei; Wan, Ning; Hou, Yi-Lin; Ma, Xi-Xi; Jia, Yi-Yang; Li, Chen; Zhou, Si-Yuan; Zhang, Bang-Le

    2016-05-15

    Cholesterol derivatives M1-M6 as synthetic cationic lipids were designed and the biological evaluation of the cationic liposomes based on them as non-viral gene delivery vectors were described. Plasmid pEGFP-N1, used as model gene, was transferred into 293T cells by cationic liposomes formed with M1-M6 and transfection efficiency and GFP expression were tested. Cationic liposomes prepared with cationic lipids M1-M6 exhibited good transfection activity, and the transfection activity was parallel (M2 and M4) or superior (M1 and M6) to that of DC-Chol derived from the same backbone. Among them, the transfection efficiency of cationic lipid M6 was parallel to that of the commercially available Lipofectamine2000. The optimal formulation of M1 and M6 were found to be at a mol ratio of 1:0.5 for cationic lipid/DOPE, and at a N/P charge mol ratio of 3:1 for liposome/DNA. Under optimized conditions, the efficiency of M1 and M6 is greater than that of all the tested commercial liposomes DC-Chol and Lipofectamine2000, even in the presence of serum. The results indicated that M1 and M6 exhibited low cytotoxicity, good serum compatibility and efficient transfection performance, having the potential of being excellent non-viral vectors for gene delivery. PMID:27072908

  5. Incorporation of a selective sigma-2 receptor ligand enhances uptake of liposomes by multiple cancer cells

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2012-08-01

    Full Text Available Yifei Zhang,1,* Yixian Huang,1,* Peng Zhang,1 Xiang Gao,1 Robert B Gibbs,2 Song Li1 1Center for Pharmacogenetics, 2Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA*These authors contributed equally to this workBackground: The sigma-2 receptor is an attractive target for tumor imaging and targeted therapy because it is overexpressed in multiple types of solid tumors, including prostate cancer, breast cancer, and lung cancer. SV119 is a synthetic small molecule that binds to sigma-2 receptors with high affinity and specificity. This study investigates the utility of SV119 in mediating the selective targeting of liposomal vectors in various types of cancer cells.Methods: SV119 was covalently linked with polyethylene glycol-dioleyl amido aspartic acid conjugate (PEG-DOA to generate a novel functional lipid, SV119-PEG-DOA. This lipid was utilized for the preparation of targeted liposomes to enhance their uptake by cancer cells. Liposomes with various SV119 densities (0, 1, 3, and 5 mole% were prepared and their cellular uptake was investigated in several tumor cell lines. In addition, doxorubicin (DOX was loaded into the targeted and unmodified liposomes, and the cytotoxic effect on the DU-145 cells was evaluated by MTT assay.Results: Liposomes with or without SV119-PEG-DOA both have a mean diameter of approximately 90 nm and a neutral charge. The incorporation of SV119-PEG-DOA significantly increased the cellular uptake of liposomes by the DU-145, PC-3, A549, 201T, and MCF-7 tumor cells, which was shown by fluorescence microscopy and the quantitative measurement of fluorescence intensity. In contrast, the incorporation of SV119 did not increase the uptake of liposomes by the normal BEAS-2B cells. In a time course study, the uptake of SV119 liposomes by DU-145 cells was also significantly higher at each time point compared to the unmodified liposomes. Furthermore, the DOX-loaded SV119 liposomes

  6. Boronated liposome development and evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Hawthorne, M.F. [Univ. of California, Los Angeles, CA (United States)

    1995-11-01

    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.

  7. Composition Influence on Pulmonary Delivery of Rifampicin Liposomes

    Directory of Open Access Journals (Sweden)

    Maria Letizia Manca

    2012-11-01

    Full Text Available The effects of lipid concentration and composition on the physicochemical properties, aerosol performance and in vitro toxicity activity of several rifampicin-loaded liposomes were investigated. To this purpose, six liposome formulations containing different amounts of soy phosphatidylcholine and hydrogenated soy phosphatidylcholine, with and without cholesterol and oleic acid, were prepared and fully characterized. Uni- or oligo-lamellar, small (~100 nm, negatively charged (~60 mV vesicles were obtained. Lipid composition affected aerosol delivery features of liposomal rifampicin; in particular, the highest phospholipid concentration led to a better packing of the vesicular bilayers with a consequent higher nebulization stability. The retention of drug in nebulized vesicles (NER% was higher for oleic acid containing vesicles (55% ± 1.4% than for the other samples (~47%. A549 cells were used to evaluate intracellular drug uptake and in vitro toxicity activity of rifampicin-loaded liposomes in comparison with the free drug. Cell toxicity was more evident when oleic acid containing liposomes were used.

  8. Preparation and evaluation of mafenide acetate liposomal formulation as eschar delivery system

    Directory of Open Access Journals (Sweden)

    Behzad Sharif Makhmalzadeh

    2011-12-01

    Full Text Available Mafenide acetate is a commonly known antimicrobial agent for wound infection. Permeability of mafenide acetate through eschar is very high and it may lead to systemic toxicity after topical application. We wish to investigate whether topical use of mafenide acetate – including vesicles could result in drug trapping in rat skin, in comparison to mafenide acetate aqueous solution. In this study, liposomes were prepared with two techniques: Solvent evaporation and Microencapsulation vesicular (MCV. We applied full factorial design for experimental design and data analysis. Drug/lipid ratio, hydration time, aqueous phase volume and homogenizer rpm were considered as independent variable, on the other hand, liposome size, drug loading, stability, drug release and skin permeability parameters as responses. The results demonstrate that liposome were multilamellar and multivesicular. Particle size and drug loading percentage of MCV liposome indicated burst sustained release profile. Burst effect in solvent evaporation liposome was more than MCV liposome. In conclusion, solvent evaporation liposome improved mafenide acetate partitioning through rat skin and decrease diffusion coefficient with increase particle size of liposome.

  9. Improved oral bioavailability of capsaicin via liposomal nanoformulation: preparation, in vitro drug release and pharmacokinetics in rats.

    Science.gov (United States)

    Zhu, Yuan; Wang, Miaomiao; Zhang, Jiajia; Peng, Wei; Firempong, Caleb Kesse; Deng, Wenwen; Wang, Qilong; Wang, Shicheng; Shi, Feng; Yu, Jiangnan; Xu, Ximing; Zhang, Weiming

    2015-04-01

    This study innovatively prepared an effective capsaicin-loaded liposome, a nanoformulation with fewer irritants, for oral administration. The in vitro and in vivo properties of the liposomal encapsulation were investigated and the potential possibility of oral administration evaluated. The liposomal agent composed of phospholipid, cholesterol, sodium cholate and isopropyl myristate was prepared using film-dispersion method. A level A in vitro-in vivo correlation (IVIVC) was established for the first time, which demonstrated an excellent IVIVC of both formulated and free capsaicin in oral administration. Physicochemical characterizations including mean particle size, zeta (ζ) potential and average encapsulation efficiency of capsaicin-loaded liposome were found to be 52.2 ± 1.3 nm, -41.5 ± 2.71 mv and 81.9 ± 2.43 %, respectively. In vivo, liposomal encapsulation allowed a 3.34-fold increase in relative bioavailability compared to free capsaicin. The gastric mucosa irritation studies indicated that the liposomal system was a safe carrier for oral administration. These results support the fact that capsaicin, an effective drug for the treatment of neuropathic pain, could be encapsulated in liposome for improved oral bioavailability. The excellent IVIVC of capsaicin-loaded liposome could also be a promising tool in liposomal formulation development with an added advantage of reduced animal testing. PMID:25231341

  10. Cell transfection in vitro and in vivo with nontoxic TAT peptide-liposome-DNA complexes

    Science.gov (United States)

    Torchilin, Vladimir P.; Levchenko, Tatyana S.; Rammohan, Ram; Volodina, Natalia; Papahadjopoulos-Sternberg, Brigitte; D'Souza, Gerard G. M.

    2003-02-01

    Liposomes modified with TAT peptide (TATp-liposomes) showed fast and efficient translocation into the cell cytoplasm with subsequent migration into the perinuclear zone. TATp-liposomes containing a small quantity (10 mol %) of a cationic lipid formed firm noncovalent complexes with DNA. Here, we present results demonstrating both in vitro and in vivo transfection with TATp-liposome-DNA complexes. Mouse NIH/3T3 fibroblasts and rat H9C2 cardiomyocytes were transfected with such complexes in vitro. The transfection with the TATp-liposome-associated pEGFP-N1 plasmid encoding for the green fluorescent protein (GFP) was high, whereas the cytotoxicity was lower than that of commonly used cationic lipid-based gene-delivery systems. Intratumoral injection of TATp-liposome-DNA complexes into the Lewis lung carcinoma tumor of mice also resulted in an expression of GFP in tumor cells. This transfection system should be useful for various protocols of cell treatment in vitro or ex vivo as well as for localized in vivo gene therapy.

  11. Effects of the protein corona on liposome-liposome and liposome-cell interactions.

    Science.gov (United States)

    Corbo, Claudia; Molinaro, Roberto; Taraballi, Francesca; Toledano Furman, Naama E; Sherman, Michael B; Parodi, Alessandro; Salvatore, Francesco; Tasciotti, Ennio

    2016-01-01

    A thorough understanding of interactions occurring at the interface between nanocarriers and biological systems is crucial to predict and interpret their biodistribution, targeting, and efficacy, and thus design more effective drug delivery systems. Upon intravenous injection, nanoparticles are coated by a protein corona (PC). This confers a new biological identity on the particles that largely determines their biological fate. Liposomes have great pharmaceutical versatility, so, as proof of concept, their PC has recently been implicated in the mechanism and efficiency of their internalization into the cell. In an attempt to better understand the interactions between nanocarriers and biological systems, we analyzed the plasma proteins adsorbed on the surface of multicomponent liposomes. Specifically, we analyzed the physical properties and ultrastructure of liposome/PC complexes and the aggregation process that occurs when liposomes are dispersed in plasma. The results of combined confocal microscopy and flow cytometry experiments demonstrated that the PC favors liposome internalization by both macrophages and tumor cells. This work provides insights into the effects of the PC on liposomes' physical properties and, consequently, liposome-liposome and liposome-cell interactions. PMID:27445473

  12. Serum insensitive, intranuclear protein delivery by the multipurpose cationic lipid SAINT-2

    NARCIS (Netherlands)

    van der Gun, Bemardina T. F.; Monami, Amlie; Laarmann, Sven; Rasko, Tamas; Slaska-Kiss, Krystyna; Weinhold, Elmar; Wasserkort, Reinhold; de Leij, Lou F. M. H.; Ruiters, Marcel H. J.; Kiss, Antal; McLaughlin, Pamela M. J.

    2007-01-01

    Cationic liposomal compounds are widely used to introduce DNA and siRNA into viable cells, but none of these compounds are also capable of introducing proteins. Here we describe the use of a cationic amphiphilic lipid SAINT-2:DOPE for the efficient delivery of proteins into cells (profection). Label

  13. Silica-Coated Liposomes for Insulin Delivery

    Directory of Open Access Journals (Sweden)

    Neelam Dwivedi

    2010-01-01

    Full Text Available Liposomes coated with silica were explored as protein delivery vehicles for their enhanced stability and improved encapsulation efficiency. Insulin was encapsulated within the fluidic phosphatidylcholine lipid vesicles by thin film hydration at pH 2.5, and layer of silica was formed above lipid bilayer by acid catalysis. The presence of silica coating and encapsulated insulin was identified using confocal and electron microscopy. The native state of insulin present in the formulation was evident from Confocal Micro-Raman spectroscopy. Silica coat enhances the stability of insulin-loaded delivery vehicles. In vivo study shows that these silica coated formulations were biologically active in reducing glucose levels.

  14. In vivo evaluation of PEGylated {sup 64}Cu-liposomes with theranostic and radiotherapeutic potential using micro PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Petersen, Anncatrine Luisa; Andresen, Thomas Lars [Technical University of Denmark, Department of Micro- and Nanotechnology, Lyngby (Denmark); Technical University of Denmark, Center for Nanomedicine and Theranostics, Lyngby (Denmark); Henriksen, Jonas Rosager [Technical University of Denmark, Center for Nanomedicine and Theranostics, Lyngby (Denmark); Technical University of Denmark, Department of Chemistry, Lyngby (Denmark); Binderup, Tina; Hag, Anne Mette; Kjaer, Andreas [University of Copenhagen, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet and Cluster for Molecular Imaging, Faculty of Health Sciences, Copenhagen (Denmark); Elema, Dennis Ringkjoebing [Technical University of Denmark, Center for Nanomedicine and Theranostics, Lyngby (Denmark); Technical University of Denmark, Center for Nuclear Technologies, Hevesy Laboratory, Roskilde (Denmark); Rasmussen, Palle Hedengran [Technical University of Denmark, Center for Nuclear Technologies, Hevesy Laboratory, Roskilde (Denmark)

    2016-05-15

    The objective of this study was to evaluate the potential of PEGylated {sup 64}Cu-liposomes in clinical diagnostic positron emission tomography (PET) imaging and PEGylated {sup 177}Lu-liposomes in internal tumor radiotherapy through in vivo characterization and dosimetric analysis in a human xenograft mouse model. Liposomes with 5 and 10 mol% PEG were characterized with respect to size, charge, and {sup 64}Cu- and {sup 177}Lu-loading efficiency. The tumor imaging potential of {sup 64}Cu-loaded liposomes was evaluated in terms of in vivo biodistribution, tumor accumulation and tumor-to-muscle (T/M) ratios, using PET imaging. The potential of PEGylated liposomes for diagnostic and therapeutic applications was further evaluated through dosimetry analysis using OLINDA/EXM software. The {sup 64}Cu-liposomes were used as biological surrogates to estimate the organ and tumor kinetics of {sup 177}Lu-liposomes. High remote loading efficiency (>95 %) was obtained for both {sup 64}Cu and {sup 177}Lu radionuclides with PEGylated liposomes, and essentially no leakage of the encapsulated radionuclide was observed upon storage and after serum incubation for 24 h at 37 C. The 10 mol% PEG liposomes showed higher tumor accumulation (6.2 ± 0.2 %ID/g) than the 5 mol% PEG liposomes, as evaluated by PET imaging. The dosimetry analysis of the {sup 64}Cu-liposomes estimated an acceptable total effective dose of 3.3.10{sup -2} mSv/MBq for diagnostic imaging in patients. A high absorbed tumor dose (114 mGy/MBq) was estimated for the potential radiotherapeutic {sup 177}Lu-liposomes. The overall preclinical profile of PEGylated {sup 64}Cu-liposomes showed high potential as a new PET theranostic tracer for imaging in humans. Dosimetry results predicted that initial administered activity of 200 MBq of {sup 64}Cu-liposomes should be acceptable in patients. Work is in progress to validate the utility of PEGylated {sup 64}Cu-liposomes in a clinical research programme. The high absorbed tumor dose

  15. Biophysical characterization of V3-lipopeptide liposomes influencing HIV-1 infectivity

    International Nuclear Information System (INIS)

    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

  16. Effects of Headgroups and Serum on Gene Transfection of Alkaline Amino Acid Based Cationic Lipids

    Institute of Scientific and Technical Information of China (English)

    LI Li; YANG Yang; NIE Yu; HE Bin; GU Zhong-wei

    2009-01-01

    Three cationic lipids with lysylated(l), histidylated(2), and arginylated(3) headgroups and cholesterol hy-drophobic moiety were synthesized. The average sizes of liposomes and lipoplexes were around 100 and 160 nm, re-spectively. The gene transfection efficiency of the three lipoplexes loaded with pGL3 or pORF-LacZ was compared on 293T cells in the presence or the absence of serum. The transfection efficiency of the three lipoplexes in a se-rum-free medium was 2 to 3-fold higher than that of dioleoyl-trimethylammonium propane(DOTAP). In the presence of serum, however, most of the lipoplexes showed lower transfection activities; only lipoplex 3 retained its high transfection efficiency.

  17. Positron Emission Tomography Based Elucidation of the Enhanced Permeability and Retention Effect in Dogs with Cancer Using Copper-64 Liposomes

    DEFF Research Database (Denmark)

    Hansen, Anders Elias; Petersen, Anncatrine Luisa; Henriksen, Jonas Rosager; Børresen, Betina; Rasmussen, Palle; Elema, Dennis Ringkjøbing; Rosenschöld, Per Munck af; Kristensen, Annemarie T.; Kjær, Andreas; Andresen, Thomas Lars

    2015-01-01

    large animals and humans with spontaneously developed cancer. In the present paper, we describe a novel loading method of copper-64 into PEGylated liposomes and use these liposomes to evaluate the EPR-effect in 11 canine cancer patients with spontaneous solid tumors by PET/CT imaging. We thereby provide...

  18. 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

  19. Functional coating of liposomes using a folate–polymer conjugate to target folate receptors

    Directory of Open Access Journals (Sweden)

    Watanabe K

    2012-07-01

    Full Text Available Kazuo Watanabe, Makoto Kaneko, Yoshie MaitaniInstitute of Medical Chemistry, Hoshi University, Tokyo, JapanAbstract: Folate-polymer-coated liposomes were developed for targeted chemotherapy using doxorubicin (DXR as a model drug. Folate-poly(L-lysine (F–PLL conjugates with a folate modification degree of 16.7 mol% on epsilon amino groups of PLL were synthesized. DXR-loaded anionic liposomes were coated with F–PLL, and the cellular association of F–PLL-coated liposomes was evaluated by flow cytometry, and confocal microscopy in human nasopharyngeal carcinoma KB cells overexpressing folate receptors (FRs, and human lung adenocarcinoma A549 cells [FR (-]. The existence of a polymer layer on the surface of F–PLL-coated liposomes was confirmed by zeta potential analysis. The KB cellular association of F–PLL-coated liposomal DXR was increased compared with that of PLL-coated liposomes and was inhibited in the presence of free folic acid. Twofold higher cytotoxicity of F–PLL-coated liposomal DXR was observed compared with that of the PLL-coated liposomal DXR in KB cells, but not in A549 cells, suggesting the presence of FR-mediated endocytosis. These results indicated that folate-targeted liposomes were prepared successfully by coating the folate–polymer conjugate F–PLL. This novel preparation method of folate-targeted liposomes is expected to provide a powerful tool for the development of a folate-targeting drug nanodevice as coating with ligand–polymer conjugates can be applicable to many kinds of particles, as well as to lipid-based particles.Keywords: cellular association, folate-targeting, liposome, poly-L-lysine, polymer coating, tumor targeting

  20. Carcinogenesis response modulation induced by gelonin encapsulated in liposome.

    Science.gov (United States)

    Alam, Anis; Nakhuru, K S; Singha, L I

    2008-08-01

    The effectiveness of gelonin to arrest protein synthesis, thereby limiting the growth of cancer cells was studied by encapsulating it into liposomes. The protein was extracted from the seeds of Indian plant Gelonium multiflorum by ammonium sulfate precipitation and purified using cation-exchange and gel-filtration chromatography. Biological activity of purified gelonin was determined using a rabbit reticulocyte lysate assay in the cell-free translational experiments. Gelonin was encapsulated in conventional liposomes prepared by the dry film method in order to retain biological activity of the entrapped protein. Carcinogenesis was induced in Swiss albino mice by intravenous administration of DBN (10 mg kg(-1) body weight) at weekly intervals. Marker enzyme assays (GGT, AChE, and GST), GSH levels, cell proliferation assay, hepatocyte DNA analysis, histological examination of micro sections of liver tissues were parameters used to monitor carcinogenesis induction, and regression in mice. From the in vitro experiments conducted, it was observed that gelonin upon its encapsulation into liposome, resulted in significant destruction of the transformed liver cells by its cytotoxic effects that arrest protein synthesis. Various parameters studied to monitor regression also suggested mass cell destruction to liver upon administration of liposomal gelonin in mice exposed to DBN. PMID:18500656

  1. Intranasal Delivery of Cationic PLGA Nano/Microparticles- Loaded FMDV DNA Vaccine Encoding IL-6 Elicited Protective Immunity against FMDV Challenge

    OpenAIRE

    Gang Wang; Li Pan; Yongguang Zhang; Yonglu Wang; Zhongwang Zhang; Jianliang Lü; Peng Zhou; Yuzhen Fang; Shoutian Jiang

    2011-01-01

    Mucosal vaccination has been demonstrated to be an effective means of eliciting protective immunity against aerosol infections of foot and mouth disease virus (FMDV) and various approaches have been used to improve mucosal response to this pathogen. In this study, cationic PLGA (poly(lactide-co-glycolide)) nano/microparticles were used as an intranasal delivery vehicle as a means administering FMDV DNA vaccine encoding the FMDV capsid protein and the bovine IL-6 gene as a means of enhancing m...

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

    Science.gov (United States)

    Smith, Cartney E; Kong, Hyunjoon

    2014-04-01

    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. PMID:24635565

  3. Propulsion of liposomes using bacterial motors

    International Nuclear Information System (INIS)

    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)

  4. Novel mucus-penetrating liposomes as a potential oral drug delivery system: preparation, in vitro characterization, and enhanced cellular uptake

    Directory of Open Access Journals (Sweden)

    Li X

    2011-12-01

    Full Text Available Xiuying Li1, Dan Chen1, Chaoyi Le2, Chunliu Zhu1, Yong Gan1, Lars Hovgaard3, Mingshi Yang41Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; 2University of Toronto Mississauga Campus, Ontario, Canada; 3Oral Formulation Development, Novo Nordisk A/S, Maalov; 4Department of Pharmaceutics and Analytical Chemistry, University of Copenhagen, Copenhagen, DenmarkBackground: The aim of this study was to investigate the intestinal mucus-penetrating properties and intestinal cellular uptake of two types of liposomes modified by Pluronic F127 (PF127.Methods: The two types of liposomes, ie, PF127-inlaid liposomes and PF127-adsorbed liposomes, were prepared by a thin-film hydration method followed by extrusion, in which coumarin 6 was loaded as a fluorescence marker. A modified Franz diffusion cell mounted with the intestinal mucus of rats was used to study the diffusion characteristics of the two types of PF127 liposomes. Cell uptake studies were conducted in Caco-2 cells and analyzed using confocal laser scanning microcopy as well as flow cytometry.Results: The diffusion efficiency of the two types of PF127-modified liposomes through intestinal rat mucus was 5–7-fold higher than that of unmodified liposomes. Compared with unmodified liposomes, PF127-inlaid liposomes showed significantly higher cellular uptake of courmarin 6. PF127-adsorbed liposomes showed a lower cellular uptake. Moreover, and interestingly, the two types of PF127-modified liposomes showed different cellular uptake mechanisms in Caco-2 cells.Conclusion: PF127-inlaid liposomes with improved intestinal mucus-penetrating ability and enhanced cellular uptake might be a potential carrier candidate for oral drug delivery.Keywords: Pluronic F127, mucus-penetrating, particles, liposomes, oral drug delivery

  5. Encapsulation of Liposomes within pH Responsive Microspheres for Oral Colonic Drug Delivery

    Directory of Open Access Journals (Sweden)

    M. J. Barea

    2012-01-01

    Full Text Available A novel liposome-in-microsphere (LIM formulation has been created comprising drug-loaded liposomes within pH responsive Eudragit S100 microspheres. The liposomes contained the model drug 5-ASA and were coated with chitosan in order to protect them during encapsulation within the microspheres and to improve site-specific release characteristics. In vitro drug release studies showed that LIMs prevented drug release within simulated stomach and small intestine conditions with subsequent drug release occurring in large intestine conditions. The formulation therefore has potential for oral colonic drug delivery.

  6. Ligand-exchange chromatographic separation of polycyclic aromatic hydrocarbons and polycyclic aromatic sulfur heterocycles on a chelating silica gel loaded with palladium (II) or silver (I) cations

    Energy Technology Data Exchange (ETDEWEB)

    Pyell, U.; Schober, S.; Stork, G. [Fachbereich Chemie der Philipps-Universitaet Marburg (Germany)

    1997-12-01

    2-Amino-1-cyclopentene-1-dithiocarboxylic acid silica gel (ACDA-SG) loaded with Ag(I) or Pd(II) ions has been examined for the group fractionation of polycyclic aromatic sulfur heterocycles (PASH) from polycyclic aromatic hydrocarbons (PAH) via ligand-exchange chromatography in the normal phase mode. It is shown that metal loading has a great impact on the selectivity of ACDA-SG for PASH and PAH. Pd(II) loaded ACDA-SG proved to be suitable for the group isolation of PASH from the aromatic fractions of petroleum mixtures (number of condensed rings{<=}3). (orig.) With 3 figs., 2 tabs., 14 refs.

  7. Comparative study of liposomes, transfersomes, ethosomes and cubosomes for transcutaneous immunisation

    DEFF Research Database (Denmark)

    Rattanapak, Teerawan; Young, Katie; Rades, Thomas;

    2012-01-01

    Objectives Lipid colloidal vaccines, including liposomes, transfersomes, ethosomes and cubosomes, were formulated, characterised and investigated for their ability to enhance penetration of a peptide vaccine through stillborn piglet skin in vitro. Methods Liposomes and transfersomes were formulated...... using a film-hydration method, ethosomes using a modified reverse phase method and cubosomes using a lipid precursor method. The size, zeta potential, peptide loading and interfacial behaviour of the formulations were characterised. Skin penetration studies were performed using Franz diffusion cells...

  8. Functional coating of liposomes using a folate–polymer conjugate to target folate receptors

    OpenAIRE

    Watanabe K.; Kaneko M; Maitani Y

    2012-01-01

    Kazuo Watanabe, Makoto Kaneko, Yoshie MaitaniInstitute of Medical Chemistry, Hoshi University, Tokyo, JapanAbstract: Folate-polymer-coated liposomes were developed for targeted chemotherapy using doxorubicin (DXR) as a model drug. Folate-poly(L-lysine) (F–PLL) conjugates with a folate modification degree of 16.7 mol% on epsilon amino groups of PLL were synthesized. DXR-loaded anionic liposomes were coated with F–PLL, and the cellular association of F–PLL-coated l...

  9. Absorption and fluorescence studies of curcumin bound to liposomes and lymphocytes: effect of γ- irradiation

    International Nuclear Information System (INIS)

    Absorption and fluorescence spectral changes in curcumin were employed to follow its binding to liposomes and lymphocytes. The association constants indicated high affinity of curcumin to liposomes. Tumor lymphocytes show mere intense fluorescence of curcumin over the normal lymphocytes. The loss of curcumin in cells after γ-irradiation could be followed by reduction in curcumin fluorescence. The studies indicate that such fluorescence changes can be used as markers to understand the preferential loading of curcumin to cells. (author)

  10. Liposomes in biology and medicine

    OpenAIRE

    Schwendener, R.

    2007-01-01

    Drug delivery systems (DDS) have become important tools for the specific delivery of a large number of drug molecules. Since their discovery in the 1960s liposomes were recognized as models to study biological membranes and as versatile DDS of both hydrophilic and lipophilic molecules. Liposomes--nanosized unilamellar phospholipid bilayer vesicles--undoubtedly represent the most extensively studied and advanced drug delivery vehicles. After a long period of research and development efforts, l...

  11. Studies on the tumor cells binding mechanism of the long-circulating liposomes loading docetaxel mediated by folic acid receptor%叶酸受体介导多西他赛长循环脂质体与肿瘤细胞结合机理的研究

    Institute of Scientific and Technical Information of China (English)

    苑振贵; 陈大为; 张守堂; 苏书华

    2011-01-01

    目的 研究叶酸受体介导多西他赛长循环脂质体与肿瘤细胞的结合机理.方法 采用薄膜分散法制备脂质体,采用荧光法、流式细胞仪和荧光显微镜检测脂质体与 MCF-7 细胞、Hela 细胞的结合.结果 叶酸受体介导多西他赛长循环脂质体与 MCF-7 细胞的结合量大于 Hela 细胞;游离叶酸可竞争抑制叶酸受体介导多西他赛长循环脂质体与 MCF-7 细胞的结合;荧光显微镜下,MCF-7细胞可见明亮绿色荧光,而 Hela 细胞中只有微弱绿色荧光.结论 叶酸受体介导多西他赛长循环脂质体是通过叶酸介导的细胞内化而进入细胞.%Objective To investigate the tumor ceils binding mechanism of the long-circulating liposomes loading docetaxel mediated by folic acid receptor(FoI-PEG-DTXL). Methods In this study, the long-circulating liposomes loading docetaxel mediated by folic acid receptor were prepared by conventional rotary-evaporated film-ultrasonication method. The flow cytometer and fluorescence microscopy were used to investigate the binding efficacy of FoI-PEG-DTXL against MCF-7 cells and Hela cells. Results After incubated with FoI-PEG-DTXL, the binding amount on MCF-7 cells was higher than that on Hela cells. The binding of Fol-PEG-DTXL could be inhabited by the addition of the free folic acid. Furthermore, a bright green fluorescence was observed on the MCF-7 cells, and the not clear green fluorescence was found on the Hela cells.Conclusions The liposomes are internalized into cells mediated by folic acid.

  12. Liposomal nanocarriers for plasminogen activators.

    Science.gov (United States)

    Koudelka, Stepan; Mikulik, Robert; Mašek, Josef; Raška, Milan; Turánek Knotigová, Pavlína; Miller, Andrew D; Turánek, Jaroslav

    2016-04-10

    Several plasminogen activators (PAs) have been found effective in treating different thromboembolic diseases. However, administration of conventional thrombolytic therapy is limited by a low efficacy of present formulations of PAs. Conventional treatments using these therapeutic proteins are associated with several limitations including rapid inactivation and clearance, short half-life, bleeding complications or non-specific tissue targeting. Liposome-based formulations of PAs such as streptokinase, tissue-plasminogen activator and urokinase have been developed to improve the therapeutic efficacy of these proteins. Resulting liposomal formulations were found to preserve the original activity of PAs, promote their selective delivery and improve thrombus targeting. Therapeutic potential of these liposome-based PAs has been demonstrated successfully in various pre-clinical models in vivo. Reductions in unwanted side effects (e.g., hemorrhage or immunogenicity) as well as enhancements of efficacy and safety were achieved in comparison to currently existing treatment options based on conventional formulations of PAs. This review summarizes present achievements in: (i) preparation of liposome-based formulations of various PAs, (ii) development of PEGylated and targeted liposomal PAs, (iii) physico-chemical characterization of these developed systems, and (iv) testing of their thrombolytic efficacy. We also look to the future and the imminent arrival of theranostic liposomal formulations to move this field forward. PMID:26876783

  13. 阳离子脂质体介导BFGF/GFP基因对药物性耳蜗损害的防治作用%Protective and rescue effects of cationic liposome - mediated bFGF/GFP on Gentamicin - induced ototoxicity in guinea pig

    Institute of Scientific and Technical Information of China (English)

    尹金淑; 翟所强; 郭维; 胡吟燕; 时利

    2003-01-01

    目的探讨阳离子脂质体(天然碱性脂SA)携带碱性成纤维细胞生长因子/绿色荧光蛋白(bFGF/GFP)基因在豚鼠耳蜗中的表达,以及对庆大霉素所致耳蜗损害的防治作用.方法将36只豚鼠分为3组,预防组右耳园窗注入SA-bFGF/GFP复合物后次日肌肉注射庆大霉素150mg.kg-1.d-18天,治疗组先用庆大霉素8 d后次日右耳给药,对照组单用庆大霉素8 d.分别于实验前后及处死前行听觉脑干诱发电位(ABR)测试.荧光显微镜下观察耳蜗GFP的表达;用耳蜗琥珀酸脱氢酶染色铺片,扫描电镜观察毛细胞的缺失情况.结果荧光显微镜下见双侧耳蜗均有GFP表达.预防和治疗组处死前的双耳ABR阈值与对照组比较差异有显著意义(P<0.01,P<0.05),耳蜗内外毛细胞缺失数与对照组比较差异有显著意义(P<0.01,P<0.05).结论SA脂质体介导的bFGF/GFP基因单耳给药双侧耳蜗均有高效表达,并对庆大霉素所致的耳蜗损害有防治作用.%Objectiye To observe the expression of cationic liposome (Stearylamine SA) mediated bFGF/GFP gene, and evaluate the efficacy of bFGF against the damage of Gentamicin in guinea pig cochlea. Methods 36 guinea pigs were divided into 3 groups. The guinea pigs in the preventive group were inoculated SA- bFGF/GFP complexes into cochleae via round window of the right ear, and were subsequently injected with Gentamicin 150mg. Kg-1 .d-1 for 8 days. The animals in the remedial group were previously administrated Gentamicin for 8 days and then received infusion of SA- bFGF/GFP complexes from nextday. The animals in the control group were only injected with Gentamicin for 8 days. Auditory brainstem response (ABR) was measured preceding test, after test and before the animals were sacrificed, respectively. ~ expression of GFP in cochlea was observed by a fluorescent microscope. The surface preparation of cochlea was made and stained with NBT for counting the absent outer and inner hair cells

  14. Co-cultivation of keratinocyte-human mesenchymal stem cell (hMSC) on sericin loaded electrospun nanofibrous composite scaffold (cationic gelatin/hyaluronan/chondroitin sulfate) stimulates epithelial differentiation in hMSCs: In vitro study.

    Science.gov (United States)

    Bhowmick, Sirsendu; Scharnweber, Dieter; Koul, Veena

    2016-05-01

    Fortifying the scaffold with bioactive molecules and glycosaminoglycans (GAGs), is an efficient way to design new generation tissue engineered biomaterials. In this study, we evaluated the synergistic effect of electrospun nanofibrous composite scaffold (cationic gelatin/hyaluronan/chondroitin sulfate) loaded with sericin and, contact co-culture of human mesenchymal stem cells (hMSCs)-keratinocytes on hMSCs' differentiation towards epithelial lineage. Cationic gelatin is prepared with one step novel synthesis process by grafting quaternary ammonium salts to the backbone of gelatin. Release kinetics studies showed that Fickian diffusion is the major release mechanism for both GAGs and sericin/gelatin. In vitro biocompatibility of the electrospun scaffold was evaluated in terms of LDH and DNA quantification assay on human foreskin fibroblast, human keratinocyte and hMSC. Significant proliferation (∼ 4-6 fold) was detected after culturing all three cell on the electrospun scaffold containing sericin. After 5 days of contact co-culture, results revealed that electrospun scaffold containing sericin promote epithelial differentiation of hMSC in terms of several protein markers (keratin 14, ΔNp63α and Pan-cytokeratin) and gene expression of some dermal proteins (keratin 14, ΔNp63α). Findings of this study will foster the progress of current skin tissue engineering scaffolds by understanding the skin regeneration and wound healing process. PMID:26946262

  15. Hyaluronic acid liposomal gel sustains delivery of a corticoid to the inner ear.

    Science.gov (United States)

    El Kechai, Naila; Mamelle, Elisabeth; Nguyen, Yann; Huang, Nicolas; Nicolas, Valérie; Chaminade, Pierre; Yen-Nicolaÿ, Stéphanie; Gueutin, Claire; Granger, Benjamin; Ferrary, Evelyne; Agnely, Florence; Bochot, Amélie

    2016-03-28

    The inner ear is one of the most challenging organs for drug delivery, mainly because of the blood-perilymph barrier. Therefore, local rather than systemic drug delivery methods are being developed for inner ear therapy. In this work, we have evaluated the benefit of a hyaluronic acid liposomal gel for sustained delivery of a corticoid to the inner ear after local injection into the middle ear in a guinea pig model. The liposomal gel was easily injectable as a result of the shear-thinning behavior of hyaluronic acid. A prolonged residence time at the site of injection as well as in the round window were achieved without any negative effect on the hearing thresholds of the animals. The presence of liposomes in the formulation resulted in sustained release of the drug in the perilymph for 30days and promoted the conversion of the prodrug loaded within the liposomes (dexamethasone phosphate) into its active form (dexamethasone). In this way, therapeutic doses were attained in the perilymph. A small amount of intact liposomes was visualized in the perilymph, whereas the main proportion of liposomes seemed to be trapped in the round window resulting in a reservoir effect. Thus, the administration of hyaluronic acid liposomal gel to the middle ear is an efficient strategy for delivering corticoids to the inner ear in a sustained manner. PMID:26860286

  16. 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. PMID:27289315

  17. Encapsulation and release of a hydrophobic drug from hydroxyapatite coated liposomes.

    Science.gov (United States)

    Xu, Qingguo; Tanaka, Yasuhiro; Czernuszka, Jan T

    2007-06-01

    Hydroxyapatite (HA) coated liposomes (HACL) have been successfully manufactured and filled with a model hydrophobic (lipophilic) drug, indomethacin (IMC). These HACL particles have been characterized in terms of particle size and zeta-potential. The liposomes are formed from 1,2-dimyristoyl-sn-glycero-3-phosphate (DMPA) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Altering their relative proportions caused the zeta-potential to change from -38.8 to -67.0 mV, with a concomitant change in phase transition temperature from 36.4 to 53.3 degrees C. These changes also affect the drug loading efficiency. The release profiles of IMC have been measured. HA coating of the liposome reduces the release rate of IMC over uncoated liposomes. Under the present experimental conditions 70% of the drug is released after approximately 5h from the liposome, but coating with HA changes this time to over 20 h. Perhaps most importantly, it has been observed that for uncoated liposomes, IMC is released at a greater rate at pH=7.4 than at pH=4. However, coating with HA reduced the rate at pH=7.4 compared to pH=4. This behaviour arises because IMC is more soluble under basic conditions, but HA is more soluble under acidic conditions. This behaviour shows that it is now possible to have environmental control over the release of drugs from HA-coated liposomes. PMID:17331574

  18. Delivering anti-cancer drugs with endosomal pH-sensitive anti-cancer liposomes.

    Science.gov (United States)

    Moku, Gopikrishna; Gulla, Suresh Kumar; Nimmu, Narendra Varma; Khalid, Sara; Chaudhuri, Arabinda

    2016-04-22

    Numerous prior studies have been reported on the use of pH-sensitive drug carriers such as micelles, liposomes, peptides, polymers, nanoparticles, etc. that are sensitive to the acidic (pH = ∼6.5) microenvironments of tumor tissues. Such systems have been primarily used in the past as effective drug/gene/microRNA carriers for releasing their anti-cancer payloads selectively to tumor cells/tissues. Herein, we report on the development of new liposomal drug carriers prepared from glutamic acid backbone-based cationic amphiphiles containing both endosomal pH-sensitive histidine as well as cellular uptake & solubility enhancing guanidine moieties in their polar head-group regions. The most efficient one among the four presently described endosomal pH-sensitive liposomal drug carriers not only effectively delivers potent anti-cancer drugs (curcumin & paclitaxel) to mouse tumor, but also significantly contributes to inhibiting mouse tumor growth. The findings in the in vitro mechanistic studies are consistent with apoptosis of tumor cells being mediated through increased cell cycle arrest in the G2/M phase. Findings in the FRET assay and in vitro drug release studies conducted with the liposomes of the most efficient pH-sensitive lipid demonstrated its pH dependent fusogenic and controlled curcumin release properties. Importantly, the presently described liposomal formulation of curcumin & paclitaxel enhanced overall survivability of tumor bearing mice. To the best of our knowledge, the presently described system (curcumin, paclitaxel and liposomal carrier itself) is the first of its kind pH-sensitive liposomal formulation of potent chemotherapeutics in which the liposomal drug itself exhibits significant mouse tumor growth inhibition properties. PMID:26806172

  19. Novel Cholesterol-Based Cationic Lipids as Transfecting Agents of DNA for Efficient Gene Delivery

    Directory of Open Access Journals (Sweden)

    Jia Ju

    2015-03-01

    Full Text Available The design, synthesis and biological evaluation of the cationic lipid gene delivery vectors based on cholesterol and natural amino acids lysine or histidine are described. Cationic liposomes composed of the newly synthesized cationic lipids 1a or 1b and neutral lipid DOPE (1,2-dioleoyl-l-α-glycero-3-phosphatidyl-ethanolamine exhibited good transfection efficiency. pEGFP-N1 plasmid DNA was transferred into 293T cells by cationic liposomes formed from cationic lipids 1a and 1b, and the transfection activity of the cationic lipids was superior (1a or parallel (1b to that of the commercially available 3β-[N-(N',N'-dimethylaminoethyl-carbamoyl] cholesterol (DC-Chol derived from the same cholesterol backbone with different head groups. Combined with the results of agarose gel electrophoresis, transfection experiments with various molar ratios of the cationic lipids and DOPE and N/P (+/− molar charge ratios, a more effective formulation was formed, which could lead to relatively high transfection efficiency. Cationic lipid 1a represents a potential agent for the liposome used in gene delivery due to low cytotoxicity and impressive gene transfection activity.

  20. Liposomal drug delivery in multimodal cancer therapy

    OpenAIRE

    2011-01-01

    Encapsulating cytostatics into lipid vesicles, i.e. liposomes, improves tumour drug accumulation and reduce adverse effects. Liposomal doxorubicin (DXR) has been used in the treatment of a variety of cancers and may also be suitable for combining with other treatment modalities. By modulating liposomal membranes, liposomes can be made ultrasound (US) sensitive releasing encapsulated drug in tumour tissue upon external US stimulation and may thereby improve therapeutic outcome. Moreover, as DX...

  1. Development of metal cation compound-loaded S-doped TiO2 photocatalysts having a rutile phase under visible light

    OpenAIRE

    Ohno, T; Murakami, N.; Tsubota, T.; Nishimura, H.

    2008-01-01

    We have synthesized S (S4+)-doped TiO2 photocatalysts having a rutile phase. Rutile S-doped TiO2 photocatalysts loaded with metal ion compounds (Fe3+, Rh3+, Cu2+, Co3+, Ni2+, Cr3+) have also been prepared (S-doped TiO2-Mn+). The metal ions were adsorbed on the surfaces of S-doped TiO2 nanoparticles by impregnation methods (IM) or photodeposition methods (PH). The photocatalytic activities of S-doped TiO2 for oxidation of acetaldehyde in gas phase were drastically improved after adsorbing trea...

  2. Fortification of dark chocolate with spray dried black mulberry (Morus nigra) waste extract encapsulated in chitosan-coated liposomes and bioaccessability studies.

    Science.gov (United States)

    Gültekin-Özgüven, Mine; Karadağ, Ayşe; Duman, Şeyma; Özkal, Burak; Özçelik, Beraat

    2016-06-15

    Fine-disperse anionic liposomes containing black mulberry (Morus nigra) extract (BME) were prepared by high pressure homogenization at 25,000 psi. Primary liposomes were coated with cationic chitosan (0.4, w/v%) using the layer-by-layer depositing method and mixed with maltodextrin (MD) (20, w/v%) prior to spray drying. After that, spray dried liposomal powders containing BME were added to chocolates with alkalization degrees (pH 4.5, 6, 7.5) at conching temperatures of 40 °C, 60 °C, and 80 °C. The results showed that, compared to spray dried extract, chitosan coated liposomal powders provided better protection of anthocyanin content in both increased temperature and pH. In addition, encapsulation in liposomes enhanced in vitro bioaccessability of anthocyanins. Chocolate was fortified with encapsulated anthocyanins maximum 76.8% depending on conching temperature and pH. PMID:26868567

  3. Dowex anion exchanger-loaded-baker's yeast as bi-functionalized biosorbents for selective extraction of anionic and cationic mercury(II) species

    International Nuclear Information System (INIS)

    Dowex anion exchanger-immobilized-baker's yeast [Dae-yeast] were synthesized and potentially applied as environmental friendly biosorbents to evaluate the up-take process of anionic and cationic mercury(II) species as well as other metal ions. Optimization of mass ratio of Dowex anion exchanger versus yeast (1:1-1:10) in presence of various interacting buffer solutions (pH 4.0-9.0) was performed and evaluated. Surface modification of [Dae-yeast] was characterized by scanning electron microscopy (SEM) and infrared spectroscopy. The maximum metal biosorption capacity values of [Dae-yeast] towards mercury(II) were found in the range of 0.800-0.960, 0.840-0.950 and 0.730-0.900 mmol g-1 in presence of buffer solutions pH 2.0, 4.0 and 7.0, respectively. Three possible and different mechanisms are proposed to account for the biosorption of mercury and mercuric species under these three buffering conditions based on ion exchange, ion pair and chelation interaction processes. Factors affecting biosorption of mercury from aqueous medium including the pH effect of aqueous solutions (1.0-7.0), shaking time (1-30 min) and interfering ions were searched. The potential applications of modified biosorbents for selective biosorption and extraction of mercury from different real matrices including dental filling waste materials, industrial waste water samples and mercury lamp waste materials were also explored. The results denote to excellent percentage extraction values, from nitric acid as the dissolution solvent with a pH 2.0, as determined in the range of 90.77-97.91 ± 3.00-5.00%, 90.00-93.40 ± 4.00-5.00% and 92.31-100.00 ± 3.00-4.00% for the three tested samples, respectively.

  4. Cationic lioposomes with folic acid as targeting ligand for gene delivery.

    Science.gov (United States)

    Cui, Shao-Hui; Zhi, De-Fu; Zhao, Yi-Nan; Chen, Hui-Ying; Meng, Yao; Zhang, Chuan-Min; Zhang, Shu-Biao

    2016-08-15

    In our previous Letter, we have carried out the synthesis of a novel DDCTMA cationic lipid which was formulated with DOPE for gene delivery. Herein, we used folic acid (FA) as targeting ligand and cholesterol (Chol) as helper lipid instead of DOPE for enhancing the stability of the liposomes. These liposomes were characterized by dynamic laser scattering (DLS), transmission electron microscopy (TEM) and agarose gel electrophoresis assays of pDNA binding affinity. The lipoplexes were prepared by using different weight ratios of DDCTMA/Chol (1:1, 2:1, 3:1, 4:1) liposomes and different concentrations of FA (50-200μg/mL) combining with pDNA. The transfection efficiencies of the lipoplexes were evaluated using pGFP-N2 and pGL3 plasmid DNA against NCI-H460 cells in vitro. Among them, the optimum gene transfection efficiency with DDCTMA/Chol (3:1)/FA (100μg/mL) was obtained. The results showed that FA could improve the gene transfection efficiencies of DDCTMA/Chol cationic liposome. Our results also convincingly demonstrated FA (100μg/mL)-coated DDCTMA/Chol (3:1) cationic liposome could serve as a promising candidate for the gene delivery. PMID:27426864

  5. Glycosaminoglycan-mediated selective changes in the aggregation states, zeta potentials, and intrinsic stability of liposomes.

    Science.gov (United States)

    Nyren-Erickson, Erin K; Haldar, Manas K; Totzauer, Jessica R; Ceglowski, Riley; Patel, Dilipkumar S; Friesner, Daniel L; Srivastava, D K; Mallik, Sanku

    2012-11-20

    Though the aggregation of glycosaminoglycans (GAGs) in the presence of liposomes and divalent cations has been previously reported, the effects of different GAG species and minor changes in GAG composition on the aggregates that are formed are yet unknown. If minor changes in GAG composition produce observable changes in the liposome aggregate diameter or zeta potential, such a phenomenon may be used to detect potentially dangerous oversulfated contaminants in heparin. We studied the mechanism of the interactions between heparin and its oversulfated glycosaminoglycan contaminants with liposomes. Herein, we demonstrate that Mg(2+) acts to shield the incoming glycosaminoglycans from the negatively charged phosphate groups of the phospholipids and that changes in the aggregate diameter and zeta potential are a function of the glycosaminoglycan species and concentration as well as the liposome bilayer composition. These observations are supported by TEM studies. We have shown that the organizational states of the liposome bilayers are influenced by the presence of GAG and excess Mg(2+), resulting in a stabilizing effect that increases the T(m) value of DSPC liposomes; the magnitude of this effect is also dependent on the GAG species and concentration present. There is an inverse relationship between the percent change in aggregate diameter and the percent change in aggregate zeta potential as a function of GAG concentration in solution. Finally, we demonstrate that the diameter and zeta potential changes in POPC liposome aggregates in the presence of different oversulfated heparin contaminants at low concentrations allow for an accurate detection of oversulfated chondroitin sulfate at concentrations of as low as 1 mol %. PMID:23102026

  6. Filter-extruded liposomes revisited

    DEFF Research Database (Denmark)

    Hinna, Askell; Steiniger, Frank; Hupfeld, Stefan; Stein, Paul C.; Kuntsche, Judith; Brandl, Martin

    (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...

  7. 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. PMID:26794740

  8. Asialoglycoprotein receptor and liposome synergistically mediate the gene transfer into primary rat hepatocytes

    Institute of Scientific and Technical Information of China (English)

    李崇辉; 温守明; 翟海峰; 孙曼霁

    1999-01-01

    Gene transfer into primary rat hepatocytes was performed by employing cationic liposome as DNA carrier and the specific ligand of hepatic asialoglycoprotein receptor (ASGPR), asialofetuin, as liver-targeting ligand. The resuits showed that asialofetuin, when added to the gene transfer complexes, could significantly increase the hepatocyte transfeetion efficiency, and alleviate the cellular toxicity of Lipofectin. Several synthetic ligands of ASGPR (galactosyl albumin) could also increase the transfection efficiency of hepatocyte like asialofetuin. It was proved that ASGPR and cationic liposome could synergistically mediate the gene transfer into primary rat hepatoeytes. This novel gene delivery system provided a safer, more simple and efficient gene transfer method for primary hepatocytes, and showed prospecting application in hepatic gene therapy.

  9. Encapsulating contact allergens in liposomes, ethosomes, and polycaprolactone may affect their sensitizing properties.

    Science.gov (United States)

    Madsen, Jakob Torp; Vogel, Stefan; Johansen, Jeanne Duus; Andersen, Klaus Ejner

    2011-06-01

    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-delivery systems: liposomes, ethosomes, and polycaprolactone particles. The results show that the drug-delivery systems are not sensitizers in themselves. Encapsulating the hydrophilic contact allergen potassium dichromate in all three drug-delivery systems did not affect the sensitizing capacity of potassium 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 for encapsulating isoeugenol in polycaprolactone (1100 ± 406) compared with a formulation in acetone:olive oil (4491 ± 819) and in liposomes (3668 ± 950). Further, the size of DNCB-loaded liposomes did not affect the sensitizing properties. These results suggest that modern dermal drug-delivery systems may in some cases magnify or decrease the sensitizing capacity of the encapsulated contact allergen. PMID:21198410

  10. The development of poly-L-arginine-coated liposomes for gene delivery

    OpenAIRE

    Opanasopit P; Tragulpakseerojn J; Apirakaramwong A; Ngawhirunpat T; Rojanarata T; Ruktanonchai U

    2011-01-01

    Praneet Opanasopit1, Jintana Tragulpakseerojn1, Auayporn Apirakaramwong1, Tanasait Ngawhirunpat1, Theerasak Rojanarata1, Uracha Ruktanonchai21Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand; 2National Nanotechnology Center, Thailand Science Park, Pathumthani, Thailand Abstract: In this study, liposomes coated with cationic polymers, poly-L-arginine (PLA), were assessed as a promising gene transfer system in human cervical carcinoma (HeLa) cells and human h...

  11. In vitro and in vivo activities of ticarcillin-loaded nanoliposomes with different surface charges against Pseudomonas aeruginosa (ATCC 29248

    Directory of Open Access Journals (Sweden)

    Gharib Amir

    2012-10-01

    Full Text Available Abstract Background Pseudomonas aeruginosa exhibits multiple antibiotic resistance mechanisms. Different studies have shown that entrapment of antibiotics into liposomes could increase their anti-Pseudomonas activity. The objectives of this study were to prepare ticarcillin loaded-nanoliposomes with variable surface charges and evaluate their in vitro and in vivo efficacies against Pseudomonas aeruginosa (ATCC 29248. Methods Ticarcillin-loaded nanoliposomes with positive, negative and neutral surface charges were prepared by extrusion method. Ticarcillin encapsulation efficacies for different formulations were measured by HPLC method. Minimum inhibitory concentration (MIC of ticarcillin nanoliposomal forms against strain ATCC 29248 were determined by broth dilution method. The killing rate of Pseudomonas aeruginosa was exposed to various concentrations of ticarcillin in free and nanoliposomal forms were analyzed. Ultimately, in vivo therapeutic efficacy of nanoliposomes in burned mice skin infected with strain ATCC 29248 was investigated. Results The encapsulation efficacies for ticarcillin-loaded cationic nanoliposomes were significantly higher (76% ± 0.17 than those of neutral (55% ± 0.14 and anionic (43% ± 0.14 nanoliposomes. The MIC of free, cationic, neutral and anionic nanoliposomal forms of ticarcillin against ATCC 29248 were to 24, 3, 6 and 48 mg/L, respectively. The killing rates of ticarcillin-loaded cationic nanoliposomes were higher than those of free and other drug formulations. Treatment by ticarcillin-loaded nanoliposomes with positive, neutral and negative surface charges resulted in almost 100, 60 and 20% survival rates, respectively. Conclusion Our data suggested that cationic ticarcillin-loaded nanoliposomes because of high effectiveness would be a good choice to treatment of Pseudomonas aeruginosa infections.

  12. Luteinizing hormone-releasing hormone receptor-mediated delivery of mitoxantrone using LHRH analogs modified with PEGylated liposomes

    OpenAIRE

    Sun, Hongfan

    2010-01-01

    Yingna He, Linhua Zhang, Cunxian SongKey Laboratory of Biomedical Material of Tianjin, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, ChinaAbstract: A sterically stabilized, mitoxantrone-loaded liposome, tailored to target luteinizing hormone-releasing hormone (LHRH) receptor overexpressing cells, was developed to promote the efficiency of intracellular delivery of mitoxantrone through receptor-mediated endocytosis. Liposome...

  13. 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.

  14. A liposomal formulation for the oral application of the investigational hepatitis B drug Myrcludex B.

    Science.gov (United States)

    Uhl, P; Helm, F; Hofhaus, G; Brings, S; Kaufman, C; Leotta, Karin; Urban, S; Haberkorn, U; Mier, W; Fricker, G

    2016-06-01

    The aim of this study was the development of a liposomal formulation containing specific tetraether lipids for the oral administration of the investigational hepatitis B peptide drug Myrcludex B. For this purpose, tetraether lipids were extracted from the extremophilic archaeon Sulfolobus acidocaldarius and purified in order to obtain the desired glycerylcaldityltetraether lipids (GCTE). Myrcludex B was synthesized by solid-phase synthesis and incorporated into liposomes containing 5mol% of GCTE. These liposomes showed a size, polydispersity index and zeta potential comparable to the standard liposomes. Cryo-EM micrographs of both liposomal formulations displayed low lamellarity, the prerequisite for high drug loading capacity. Long term storage of the GCTE-liposomes was achieved by freeze-drying using 100-500mM sucrose or trehalose as lyoprotectors. The lyophilized product showed high stability with a recovery rate of 82.7±1.6% of intact Myrcludex B observed after storage for 3months at -20°C as compared to a recovery rate of 83.3±1.3% directly after the freeze-drying process. In vivo, the GCTE-liposomal formulation led to substantial enhancement of the liver uptake of iodine-131-labeled Myrcludex B in Wistar rats. 3h after oral application, approximately 7% of the initial dose (corresponding to a 3.5-fold increase compared to the free peptide) could be detected in the liver. In summary, the GCTE-liposomes enabled efficient oral administration of Myrcludex B and provided long term storage by freeze-drying. PMID:27049970

  15. Size of thermosensitive liposomes influences content release.

    Science.gov (United States)

    Hossann, Martin; Wang, Tungte; Wiggenhorn, Michael; Schmidt, Rebecca; Zengerle, Anja; Winter, Gerhard; Eibl, Hansjörg; Peller, Michael; Reiser, Maximilian; Issels, Rolf D; Lindner, Lars H

    2010-11-01

    Thermosensitive liposomes (TSL) in combination with regional hyperthermia represent a powerful tool for tumor specific drug delivery. The objective of this study was to investigate the influence of vesicle size on the biophysical properties of TSL. TSL were composed of DPPC/DSPC/1,2-dipalmitoyl-sn-glycero-3-phosphoglyceroglycerol (DPPG(2)) 50:20:30 (mol/mol) (DPPG(2)-TSL) and DPPC/P-Lyso-PC/DSPE-PEG2000 90:10:4 (mol/mol) (PEG/Lyso-TSL) with encapsulated fluorescent dye carboxyfluorescein, anticancer drug doxorubicin or magnetic resonance contrast agent gadodiamide. Extrusion was performed with polycarbonate filters of distinct pore size to obtain TSL with different diameters (50 to 200nm). Phase transition temperature (T(m)) of the bilayer forming phospholipids was not influenced by vesicle size in the tested range. However, vesicle size had a major impact on in vitro content release properties of TSL in the investigated temperature range between 30 and 45°C. Generally, vesicle size was inversely related to content release properties with increased content release rates for decreased vesicle sizes. Size dependency of content release properties varied between all tested formulations and DPPG(2)-TSL were generally less affected by size changes in the range of 100 to 150nm as compared to PEG/Lyso-TSL. Independent from gadodiamide release, vesicle size influenced the signal intensity of DPPG(2)-TSL also at temperatures below T(m) due to improved water exchange for smaller vesicles. Liposomes around 100nm in size are routinely used in vivo, hence a quality control for TSL preparations is required prior to use. Even small changes in size or a wider size distribution might affect stability and release properties and thus yield in decreased efficacy or unwanted side effects of drug loaded TSL during in vivo applications. PMID:20727921

  16. Photodynamic ultradeformable liposomes: Design and characterization.

    Science.gov (United States)

    Montanari, J; Perez, A P; Di Salvo, F; Diz, V; Barnadas, R; Dicelio, L; Doctorovich, F; Morilla, M J; Romero, E L

    2007-02-01

    Hydrophobic ([tetrakis(2,4-dimetil-3-pentyloxi)-phthalocyaninate]zinc(II)) (ZnPc) and hydrophilic ([tetrakis(N,N,N-trimethylammoniumetoxi)-phthalocyaninate]zinc(II) tetraiodide) (ZnPcMet) phthalocyanines were synthesized and loaded in ultradeformable liposomes (UDL) of soybean phosphatidylcholine and sodium cholate (6:1, w/w, ratio), resulting 100 nm mean size vesicles of negative Zeta potential, with encapsulation efficiencies of 85 and 53%, enthalpy of phase transition of 5.33 and 158 J/mmol for ZnPc and ZnPcMet, respectively, indicating their deep and moderate partition into UD matrices. Matrix elasticity of UDL-phthalocyanines resulted 28-fold greater than that of non-UDL, leaking only 25% of its inner aqueous content after passage through a nanoporous barrier versus 100% leakage for non-UDL. UDL-ZnPc made ZnPc soluble in aqueous buffer while kept the monomeric state, rendering singlet oxygen quantum yield (Phi(Delta)) similar to that obtained in ethanol (0.61), whereas UDL-ZnPcMet had a four-fold higher Phi(Delta) than that of free ZnPcMet (0.21). Free phthalocyanines were non-toxic at 1 and 10 microM, both in dark or upon irradiation at 15 J/cm2 on Vero and J-774 cells (MTT assay). Only liposomal ZnPc at 10 microM was toxic for J-774 cells under both conditions. Additionally, endo-lysosomal confinement of the HPTS dye was kept after irradiation at 15 J/cm2 in the presence of UDL-phtalocyanines. This could lead to improve effects of singlet oxygen against intra-vesicular pathogen targets inside the endo-lysosomal system. PMID:17157460

  17. Hyaluronic acid-coated liposomes for targeted delivery of paclitaxel, in-vitro characterization and in-vivo evaluation.

    Science.gov (United States)

    Ravar, Fatemeh; Saadat, Ebrahim; Gholami, Mehdi; Dehghankelishadi, Pouya; Mahdavi, Mehdi; Azami, Samira; Dorkoosh, Farid A

    2016-05-10

    Breast cancer is the leading cause of cancer death in women. Chemotherapy is regarded as the most essential strategy in inhibiting the proliferation of tumor cells. Paclitaxel is a widely used taxane; however, the side effects of available Cremophor-based formulations and also the limitations of passive targeting uncovered an essential need to develop tumor-specific targeted nanocarriers. A hyaluronic acid targeted liposomal formulation of paclitaxel was prepared in which, hyaluronic acid was electrostatistically attracted to the surface of liposomes. Liposomes, had a particle size of 106.4±3.2nm, a weakly negative zeta potential of -9.7±0.8mV and an acceptable encapsulation efficiency of 92.1±1.7%. The release profile of liposomes in buffer showed that 95% of PTX was released during 40h. Confocal laser scanning microscopy and flow cytometry analysis showed the greater cellular internalization of coumarin-loaded liposomes compared to free coumarin. MTT assay on 4T1 and T47D cells demonstrated the stronger cytotoxic activity of liposomes in comparison to free paclitaxel. Cell cycle analysis showed that cells were mainly blocked at G2/M phases after 48h treatment with liposomes. In vivo real time imaging on 4T1 tumor-bearing mice revealed that the liposomal formulation mainly accumulated in the tumor area. Liposomes also had better antitumor efficacy against Cremophor-based formulation. In conclusion, hyaluronic acid targeted paclitaxel liposome can serve as a promising targeted formulation of paclitaxel for future cancer chemotherapy. PMID:26968799

  18. Adjuvant effects of liposomes containing lipid A: enhancement of liposomal antigen presentation and recruitment of macrophages.

    OpenAIRE

    Verma, J N; Rao, M.; Amselem, S; Krzych, U; Alving, C R; Green, S J; Wassef, N M

    1992-01-01

    Liposomes containing lipid A induced potent humoral immune responses in mice against an encapsulated malaria antigen (R32NS1) containing NANP epitopes. The immune response was not enhanced by lipid A alone or by empty liposomes containing lipid A. Experiments to investigate the adjuvant mechanisms of liposomes and lipid A revealed that liposome-encapsulated R32NS1 was actively presented by bone marrow-derived macrophages to NANP-specific cloned T cells. The degree of presentation was related ...

  19. Comparison of Conventional Chemotherapy, Stealth Liposomes and Temperature-Sensitive Liposomes in a Mathematical Model

    OpenAIRE

    GASSELHUBER, ASTRID; Dreher, Matthew R.; Rattay, Frank; Bradford J. Wood; Haemmerich, Dieter

    2012-01-01

    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 ...

  20. 多肽修饰载紫杉醇脂质体靶向A549肺癌干细胞的研究%Study on the ability of specific-binding peptide modified liposome loaded paclitaxel targeting A549 lung cancer stem cell

    Institute of Scientific and Technical Information of China (English)

    蔡华荣; 江跃全

    2014-01-01

    Objective To prepare CD133 specific-binding peptide conjugated liposome loaded paclitaxel and evaluate the efficiency of cellular uptake and the ability of inhibiting A549 lung cancer stem cell.Methods Liposomes were prepared by film-ultrasonic method.The partical size,zeta-potential and entrapment efficiency of liposomes were evaluated.Cellular uptake effciency of A549 lung cancer stem cell for liposomes were explored.The anti-proliferation efficiency of TLP-PTX to A549 lung cancer stem cell was evaluated by MTT assay.Tumor spheroids were used to evaluate anti-tumor ability of TLP-PTX to A549 lung cancer stem cell. Results The particle diameter of TLP-PTX was (115.8 ±8.3)nm and the entrapment efficiency of PTX was 88.5%.CD133 specific-binding peptide could enhance the efficiency of cellar uptake.The uptaken efficiency of TLP by A549 lung cancer stem cell were 2.6 times higher than that of LP(P<0.05 ).The MTT Results showed that the toxicity of TLP-PTX on A549 lung cancer stem cell was significantly stronger than LP-PTX and paclitaxel solution(P<0.05 ).The tumor inhibition test results showed that TLP-PTX has good anti-tumor effect. Conclusion TLP-PTX can specifically recognize the surface marker CD133 of A549 lung cancer stem cell,facilitate liposomes into cells and inhibit A549 lung cancer stem cell proliferation.TLP-PTX is an effective drug delivery system targeting to A549 lung cancer stem cell.%目的:制备与肺癌干细胞标志物CD133具有高度亲和力的多肽修饰载紫杉醇脂质体(CD133 specific-binding peptide conjugated paclitaxel loaded liposome,TLP-PTX),考察TLP-PTX与A549肺癌干细胞的结合能力及其对A549肺癌干细胞和肺癌干细胞移植瘤的抑制作用。方法采用薄膜分散法制备TLP-PTX,观察其粒径,电位及紫杉醇的包封率等理化性质。采用细胞摄取实验和肿瘤球穿透实验考察TLP-PTX与A549肺癌干细胞的亲和力。通过MTT实验和肺癌干细胞肿瘤球抑制实

  1. Application of Liposomes in Some Dairy Products.

    Science.gov (United States)

    Khanniri, E; Bagheripoor-Fallah, N; Sohrabvandi, S; Mortazavian, A M; Khosravi-Darani, K; Mohammad, R

    2016-01-01

    The application of liposomes as potential carriers to deliver food components is considerably an innovative technology. While the application of liposome technology has been very limited to date, researches indicating the potential of liposomes for improving the flavor of ripened cheese using accelerated methods, the targeted delivery of functional food ingredients, the synergistic delivery of ascorbic acid and tocopherols for promoting antioxidant activity in foods, and the stabilization of minerals (such as iron) in milk have been performed. In the food industry, liposomes and nanoliposomes have been employed to encapsulate flavoring and nutritive agents, and also, they have been suitable candidates to deliver antimicrobials. In this paper, application of lipase, proteinase, nisin, and flavor-containing liposomes in products during the processing (such as cheese maturity) as well as the application of liposomes-encapsulated micronutrients (such as iron) in milk are reviewed. PMID:25574577

  2. 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

  3. Liposomes - experiment of magnetic resonance imaging application

    International Nuclear Information System (INIS)

    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

  4. Liposomes in Double-Emulsion Globules

    OpenAIRE

    Wang, Qing; Tan, Grace; Lawson, Louise B.; John, Vijay T.; Papadopoulos, Kyriakos D.

    2010-01-01

    Tubular liposomes containing a hydrophilic model compound (fluorescein sodium salt, FSS) were entrapped inside the internal aqueous phase (W1) of water-in-oil-in-water (W1/O/W2) double-emulsion globules. Our hypothesis was that the oil membrane of double emulsions can function as a layer of protection to liposomes and their contents and thus better control their release. Liposomes were prepared in bulk, and their release was observed microscopically from individual double-emulsion globules. T...

  5. Liposomal Encapsulated Rhodomyrtone: A Novel Antiacne Drug

    OpenAIRE

    Julalak Chorachoo; Thanaporn Amnuaikit; Voravuthikunchai, Supayang P.

    2013-01-01

    Rhodomyrtone isolated from the leaves of Rhodomyrtus tomentosa possesses antibacterial, anti-inflammatory, and anti-oxidant activities. Since rhodomyrtone is insoluble in water, it is rather difficult to get to the target sites in human body. Liposome exhibited ability to entrap both hydrophilic and hydrophobic compounds and easily penetrate to the target site. The present study aimed to develop a novel liposomal encapsulated rhodomyrtone formulations. In addition, characterization of liposom...

  6. Design of liposomal formulations for cell targeting

    OpenAIRE

    Nogueira, E.; Gomes, Andreia C.; Preto, Ana; Cavaco-Paulo, Artur

    2015-01-01

    Liposomes have gained extensive attention as carriers for a wide range of drugs due to being both nontoxic and biodegradable as they are composed of substances naturally occurring in biological membranes. Active targeting for cells has explored specific modification of the liposome surface by functionalizing it with specific targeting ligands in order to increase accumulation and intracellular uptake into target cells. None of the Food and Drug Administration-licensed liposomes or lipid nanop...

  7. Synthesis and characterization of liposomes nano-composite-particles with hydrophobic magnetite as a MRI probe

    Science.gov (United States)

    Han, Limin; Zhou, Xingping

    2016-07-01

    Nano-magnetic liposomes (MLs) consist of liposomes and magnetic nanoparticles (MNPs). Due to the active surfaces of liposomes, various functional groups can be attached for ligand-specific targeting. Here, we describe synthesis of magnetic nano-composite liposomes (HMLs) by a thin film dispersing method, based on hydrophobic magnetite (Fe3O4) nanoparticles. The results showed that the particle diameter of the HMLs containing Fe3O4sbnd OA NPs at a final Fe loading of 11.02 g/mol phosphatidylcholine (POPC) mainly in a sandwich-structure was 125.3 ± 12.9 nm determined by transmission electron microscopy (TEM) and dynamic light scattering (DLS). While the initial Fe concentration in the solution varied from 0.25 to 3.0 mg/mL, an effective Fe3O4 NPs loading was achieved, with encapsulation efficiency (EE%) from 91.0% to 71.0%. Subsequently, the HMLs were confirmed to be quite cytocompatible and hemocompatible in the applied concentration range by MTT and hemolysis assays. We also found that HMLs had more advantages than those liposomes with hydrophilic Fe3O4 NPs by comparing their EE% and r2 relaxivity. Finally, it was concluded that the analyzed Fe concentration in HMLs was sufficient to produce a pronouncedly weak signal for MRI in vitro to enhance the contrast between tumors and normal tissues.

  8. An interaction of helicid with liposome biomembrane

    International Nuclear Information System (INIS)

    An interaction of helicid with phosphatidylcholine liposome biomembrane was studied by transmission electron microscopy, UV-vis, fluorescence, Raman and 31P NMR spectra. The results indicate that most of helicid molecules associate with liposomes at their surface and some of them penetrate the liposomes and locate in the hydrophobic regions of the membrane. The distribution coefficient KD between liposome phases and aqueous phases is 13.5. The liposome becomes more dispersive and stable in the presence of helicid. The microenvironmental micropolarity and the microhydrophobicity of liposome membrane decrease with the increase of helicid concentration. The interaction of helicid molecules with liposome results in a slight decrease of the membrane longitudinal order, and an increase of the membrane lateral order. A model for the interaction of helicid with liposome biomembrane is proposed on the basis of the change of microenvironment parameters of liposome including the micropolarity, microhydrophobicity and membrane order. The change of microenvironment parameters results mainly from hydrogen bonding interaction between the hydroxyl groups of the pyranoside rings of helicid molecules and the polar head groups of phosphatidylcholine.

  9. DNA controlled assembly of liposomes

    DEFF Research Database (Denmark)

    Vogel, Stefan; Jakobsen, Ulla; Simonsen, Adam Cohen

    2009-01-01

    DNA-encoding of solid nanoparticles requires surfacechemistry, which is often tedious and not generally applicable. In the present study non-covalently attached DNA are used to assemble soft nanoparticles (liposomes) in solution. This process displays remarkably sharp thermal transitions from...... assembled to disassembled state for which reason this method allows easy and fast detection of polynucleotides (e.g. DNA or RNA), including single nucleotide polymorphisms as well as insertions and deletions....

  10. Positron emission tomography evaluation of somatostatin receptor targeted (64)Cu-TATE-liposomes in a human neuroendocrine carcinoma mouse model

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa; Binderup, Tina; Jølck, Rasmus Irming;

    2012-01-01

    -liposomes without TATE. PEGylated liposomes with or without TATE accumulated at significantly higher quantities in NETs (5.1±0.3 and 5.8±0.2 %ID/g, respectively) than the free peptide (64)Cu-DOTA-TATE (1.4±0.3 %ID/g) 24h post-injection. Importantly, (64)Cu-loaded PEGylated liposomes with TATE showed significantly...... higher tumor-to-muscle (T/M) ratio (12.7±1.0) than the control-liposomes without TATE (8.9±0.9) and the (64)Cu-DOTA-TATE free peptide (7.2±0.3). The higher T/M ratio of the PEGylated liposomes with TATE suggests some advantage of active targeting of NETs, although no absolute benefit in tumor...... image NETs was evaluated using PET. Additionally, the liposome accumulation and imaging capability was compared with free radiolabelled TATE peptide administered as (64)Cu-DOTA-TATE. The presence of TATE on the liposomes resulted in a significantly faster initial blood clearance in comparison to control...

  11. Two cholesterol derivative-based PEGylated liposomes as drug delivery system, study on pharmacokinetics and drug delivery to retina

    Science.gov (United States)

    Geng, Shengyong; Yang, Bin; Wang, Guowu; Qin, Geng; Wada, Satoshi; Wang, Jin-Ye

    2014-07-01

    In this study, two cholesterol derivatives, (4-cholesterocarbonyl-4‧-(N,N,N-triethylamine butyloxyl bromide) azobenzene (CAB) and 4-cholesterocarbonyl-4‧-(N,N-diethylamine butyloxyl) azobenzene (ACB), one of which is positively charged while the other is neutral, were synthesized and incorporated with phospholipids and cholesterol to form doxorubicin (DOX)-loaded liposomes. PEGylation was achieved by including 1,2-distearoyl-sn-glycero-3-phosphatiylethanol-amine-N-[methoxy-(polyethylene glycol)-2000 (DSPE-PEG2000). Our results showed that PEGylated liposomes displayed significantly improved stability and the drug leakage was decreased compared to the non-PEGylated ones in vitro. The in vivo study with rats also revealed that the pharmacokinetics and circulation half-life of DOX were significantly improved when liposomes were PEGylated (p cholesterol derivative ACB played some role in improving liposomes’ stability in systemic circulation compared to the conventional PC liposome and the positively charged CAB liposome, with or without PEGylation. In addition, in the case of local drug delivery, the positively charged PEG-liposome not only delivered much more of the drug into the rats’ retinas (p , but also maintained much longer drug retention time compared to the neutral PEGylated liposomes.

  12. Biophysical studies on chitosan-coated liposomes.

    Science.gov (United States)

    Mady, Mohsen M; Darwish, Mirhane M; Khalil, Safaa; Khalil, Wafaa M

    2009-10-01

    Liposomes have been used as delivery vehicles for stabilizing drugs, overcoming barriers to cellular and tissue uptake, and for directing their contents toward specific sites in vivo. Chitosan is a biological macromolecule derived from crustacean shells and has several emerging applications in drug development, obesity control, and tissue engineering. In the present work, the interaction between chitosan and dipalmitoyl phosphatidylcholine (DPPC) liposomes was studied by transmission electron microscopy (TEM), zeta potential, solubilization using the nonionic detergent octylglucoside (OG), as well as Fourier transform infrared (FTIR) spectroscopy and viscosity measurements. The coating of DPPC liposomes by a chitosan layer was confirmed by electron microscope images and the zeta potential of liposomes. Coating of liposome by chitosan resulted in an increase in liposomal size by addition of a layer of 92 +/- 27.1 nm. The liposomal zeta potential became increasingly positive as chitosan concentration increased from 0.1 to 0.3% w/v, then it held at a relatively constant value. The amount of detergent needed to completely solubilize the liposomal membrane was increased after coating of liposomes with chitosan, indicating an increased membrane resistance to the detergent and hence a change in the natural membrane permeation properties. In the analysis of FTIR spectra of DPPC, the symmetric and antisymmetric CH(2) (at 2,800-3,000 cm(-1)) bands and the C=O (at 1,740 cm(-1)) stretching band were investigated in the absence and presence of the chitosan. It was concluded that appropriate combining of the liposomal and chitosan characteristics might be utilized for the improvement of the therapeutic efficacy of liposomes as a drug delivery system. PMID:19649627

  13. Development of the Liposomes Entrapped Ultrasound Imaging Gas (``Bubble Liposomes'') as Novel Gene Delivery Carriers

    Science.gov (United States)

    Suzuki, Ryo; Tanaka, Kumiko; Sawamura, Kaori; Takizawa, Tomoko; Utoguchi, Naoki; Negishi, Yoichi; Hagisawa, Kohsuke; Nishioka, Toshihiko; Maruyama, Kazuo

    2006-05-01

    Recently, microbubbles and ultrasound have been investigated with a view to improving the transfection efficiency of nonviral delivery systems for gene by cavitation. However, microbubbles had some problems in terms of stability and targeting ability. To solve these problems, we paid attention to liposomes that had many advantages such as stable and safe in vivo and easy to modify targeting ligand. Previously, we have represented that liposomes are good drug and gene delivery carriers. In addition, we developed that the liposomes ("Bubble liposomes") were entrapped with perfluoropropane known as ultrasound imaging gas. In this study, we assessed about feasibility of "Bubble liposomes" as gene delivery tool utilized cavitation by ultrasound irradiation. "Bubble liposomes" could effectively deliver plasmid DNA to cells by combination of ultrasound irradiation without cyototoxicity. This result suggested that "Bubble liposomes" might be a new class of tool for gene delivery.

  14. Mild Hyperthermia and Thermosensitive Liposomes for Chemotherapy

    NARCIS (Netherlands)

    L. Li (Li)

    2013-01-01

    textabstractLiposomes are nano-sized drug carriers widely used to deliver chemotherapeutic compounds in cancer treatments. While prolonging drug retention in circulation and preventing certain toxic side-effects, liposomal drugs still need to overcome matters on specific accumulation in the tumor an

  15. Anomalous freezing behavior of nanoscale liposomes

    DEFF Research Database (Denmark)

    Spangler, E. J.; Kumar, P. B. S.; Laradji, M.

    2012-01-01

    The effect of the finite size of one-component liposomes on their phase behavior is investigated via simulations of an implicit-solvent model of self-assembled lipid bilayers. We found that the high curvature of nanoscale liposomes has a significant effect on their freezing behavior. While the lo...

  16. Phospholipase A(2)-susceptible liposomes of anticancer double lipid-prodrugs.

    Science.gov (United States)

    Arouri, Ahmad; Mouritsen, Ole G

    2012-03-12

    A novel approach to anticancer drug delivery is presented based on lipid-like liposome-forming anticancer prodrugs that are susceptible to secretory phospholipase A(2) (sPLA(2)) that is overexpressed in several cancer types. The approach provides a selective unloading of anticancer drugs at the target tissues, as well as circumvents the necessity for "conventional" drug loading. In our attempts to improve the performance of the liposomes in vivo, several PEGylated and non-PEGylated liposomal formulations composed of a retinoid prodrug premixed with the sPLA(2)-hydrolyzable DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) were prepared. Besides favorably modifying the physicochemical properties of the liposomes, the incorporation of DPPC and PEG-lipids in the liposomes should substantially enhance the enzymatic activity, as concluded from literature. In addition, one can reap benefits from the presumed permeability enhancing effect of the liberated fatty acids and lysolipids. The size distribution of the prepared liposomes as well as their phase behavior, enzymatic hydrolysis, and cytotoxicity, in the presence and absence of sPLA(2), were determined. The liposomes were around 100nm in diameter and in the gel/fluid coexistence region at 37°C. The enzymatic hydrolysis of the prodrug was pronouncedly accelerated upon the premixing with DPPC, and the hydrolysis was further enhanced by PEGylation. Interestingly, the faster hydrolysis of the prodrug and the released fatty acids and lysolipids from DPPC did not improve the cytotoxicity of the mixture; the effect of combining the prodrug with DPPC was additive and not synergistic. The data presented here question the significance of the permeability enhancing effects claimed for fatty acids and lysolipids at the target cell membrane, and whether these effects can be achieved using physiologically achievable concentrations of fatty acids and lysolipids. PMID:21946258

  17. A diaCEST MRI approach for monitoring liposomal accumulation in tumors.

    Science.gov (United States)

    Chan, Kannie W Y; Yu, Tao; Qiao, Yuan; Liu, Qiang; Yang, Ming; Patel, Himatkumar; Liu, Guanshu; Kinzler, Kenneth W; Vogelstein, Bert; Bulte, Jeff W M; van Zijl, Peter C M; Hanes, Justin; Zhou, Shibin; McMahon, Michael T

    2014-04-28

    Nanocarrier-based chemotherapy allows preferential delivery of therapeutics to tumors and has been found to improve the efficacy of cancer treatment. However, difficulties in tracking nanocarriers and evaluating their pharmacological fates in patients have limited judicious selection of patients to those who might most benefit from nanotherapeutics. To enable the monitoring of nanocarriers in vivo, we developed MRI-traceable diamagnetic Chemical Exchange Saturation Transfer (diaCEST) liposomes. The diaCEST liposomes were based on the clinical formulation of liposomal doxorubicin (i.e. DOXIL®) and were loaded with barbituric acid (BA), a small, organic, biocompatible diaCEST contrast agent. The optimized diaCEST liposomal formulation with a BA-to-lipid ratio of 25% exhibited 30% contrast enhancement at B1=4.7μT in vitro. The contrast was stable, with ~80% of the initial CEST signal sustained over 8h in vitro. We used the diaCEST liposomes to monitor the response to tumor necrosis factor-alpha (TNF-α), an agent in clinical trials that increases vascular permeability and uptake of nanocarriers into tumors. After systemic administration of diaCEST liposomes to mice bearing CT26 tumors, we found an average diaCEST contrast at the BA frequency (5ppm) of 0.4% at B1=4.7μT while if TNF-α was co-administered the contrast increased to 1.5%. This novel approach provides a non-radioactive, non-metallic, biocompatible, semi-quantitative, and clinically translatable approach to evaluate the tumor targeting of stealth liposomes in vivo, which may enable personalized nanomedicine. PMID:24548481

  18. Scintigraphic evaluation of 99mTc labelled liposomal dispersion containing tropicamide for ocular delivery

    International Nuclear Information System (INIS)

    Full text: Bioavailability of drug administered topically in the liquid dosage form to the eye is limited due to rapid pre corneal clearance resulting from solution drainage and also spillage from palpebral fissure. With the objective of improving utilisation of drug by increasing its residence time in eye, topicamide, a mydriatic and cycloplegic agent was encapsulated into liposomes. Multi lamellar liposomes were prepared from soya phosphatidylcholine in combination with cholesterol, employing conventional lipid film hydration technique. Liposome dispersion was labelled with 99mTc-pertechnetate about 50 μCi in 15 μl of preparation was instilled in the eyes of the rabbit and dacryoscintigraphy was performed on a gamma camera fitted with a pinhole collimator. Dynamic and static images were taken. Three regions of interest namely conjunctival space, lacrimal sac and naso-lacrimal duct were marked and radioactivity in these regions over 10 minutes period was computed and compared with 99mTc-DTPA in aqueous phase. From these studies it was evident that there was increase in the residence time of liposome-bound radioactivity. Further, there was slower drainage of activity into lacrimal sac and nasolacrimal duct compared to 99mTc-DTPA. The half clearance times of activity in conjunctival space for Tc-DTPA, empty liposomes and drug-loaded liposomes were 3.22,15.21 and 16.8 min, respectively, while for lacrimal sac the values were 13.94, 29.09 and 29.2 min, respectively. This characteristic of the liposome-bound drug may be important in prolonging the therapeutic effect observed by us in rabbits

  19. Do plasma proteins distinguish between liposomes of varying charge density?

    KAUST Repository

    Capriotti, Anna Laura

    2012-03-01

    Cationic liposomes (CLs) are one of the most employed nonviral nanovector systems in gene therapy. However, their transfection efficiency is strongly affected by interactions with plasma components, that lead to the formation of a "protein corona" onto CL surface. The interactions between nanoparticles entering the body and biomolecules have an essential role for their biodistribution. Because the knowledge of proteins adsorbed onto vector surface could be useful in the screening of new, more efficient and more biocompatible liposomal formulations, the behavior of three CLs with different membrane charge densities was investigated. The proteins of the three coronas were identified by nano-liquid chromatography-tandem mass spectrometry, and quantified with label-free spectral counting strategy. Fibrinogen displayed higher association with CLs with high membrane charge density, while apolipoproteins and C4b-binding protein with CLs with low membrane charge density. These results are discussed in terms of the different lipid compositions of CLs and may have a deep biological impact for in vivo applications. Surface charge of nanoparticles is emerging as a relevant factor determining the corona composition after interaction with plasma proteins. Remarkably, it is also shown that the charge of the protein corona formed around CLs is strongly related to their membrane charge density. © 2012 Elsevier B.V.

  20. Influence of massage and occlusion on the ex vivo skin penetration of rigid liposomes and invasomes

    DEFF Research Database (Denmark)

    Trauer, S.; Richter, H.; Kuntsche, Judith;

    2014-01-01

    Liposomes are frequently described as drug delivery systems for dermal and transdermal applications. Recently, it has been shown that particulate substances penetrate effectively into hair follicles and that the follicular penetration depth can be increased by massaging the skin, which simulates...... the in vivo movement of hairs in the hair follicles. In the present study, massage was applied to skin mounted to Franz diffusion cells. By means of confocal laser scanning microscopy, the influence of massage and occlusion on the follicular penetration depths of rigid and flexible liposomes loaded...... with a hydrophilic and lipophilic dye was investigated. The application of massage increased follicular penetration significantly. Occlusion resulted in an increased follicular penetration depth only for rigid liposomes, whereas invasomes did not penetrate more effectively if occlusion was applied. The...

  1. The potential of transferrin-pendant-type polyethyleneglycol liposomes encapsulating decahydrodecaborate-1B (GB-10) as 1B-carriers for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Purpose: To evaluate GB-10-encapsulating transferrin (TF)-pendant-type polyethyleneglycol (PEG) liposomes as tumor-targeting 1B-carriers for boron neutron capture therapy. Methods and Materials: A free mercaptoundecahydrododecaborate-1B (BSH) or decahydrodecaborate-1B (GB-10) solution, bare liposomes, PEG liposomes, or TF-PEG liposomes were injected into SCC VII tumor-bearing mice, and 1B concentrations in the tumors and normal tissues were measured by γ-ray spectrometry. Meanwhile, tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all intratumor proliferating cells, then injected with these 1B-carriers containing BSH or GB-10 in the same manner. Right after thermal neutron irradiation, the response of quiescent (Q) cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. The frequency in the total tumor cells was determined from the BrdU nontreated tumors. Results: Transferrin-PEG liposomes showed a prolonged retention in blood circulation, low uptake by reticuloendothelial system, and the most enhanced accumulation of 1B in solid tumors. In general, the enhancing effects were significantly greater in total cells than Q cells. In both cells, the enhancing effects of GB-10-containing 1B-carriers were significantly greater than BSH-containing 1B-carriers, whether loaded in free solution or liposomes. In both cells, whether BSH or GB-10 was employed, the greatest enhancing effect was observed with TF-PEG liposomes followed in decreasing order by PEG liposomes, bare liposomes, and free BSH or GB-10 solution. In Q cells, the decrease was remarkable between PEG and bare liposomes. Conclusions: In terms of biodistribution characteristics and tumor cell-killing effect as a whole, including Q cells, GB-10 TF-PEG liposomes were regarded as promising 1B-carriers

  2. The structure and behavior of the NA-CATH antimicrobial peptide with liposomes.

    Science.gov (United States)

    Du, Haijuan; Samuel, Robin L; Massiah, Michael A; Gillmor, Susan D

    2015-10-01

    Naja atra cathelicidin (NA-CATH) is a 34-amino acid highly cationic peptide identified in Chinese cobras to possess potent toxicity against gram-negative and gram-positive bacteria and low toxicity against host cells. Here, we report the NMR solution structure of the full-length NA-CATH peptide and its interaction with liposomes. The structure shows a well-defined α-helix between residues Phe3 to Lys23, on which one surface is lined by the side-chains of one arginine and 11 lysine residues, while the other side is populated by hydrophobic residues. The last eleven amino acids, which are predominately aromatic and hydrophobic in nature, have no defined structure. NMR data reveal that these residues do not interact with the hydrophobic residues of the helix, indicating that the C-terminal residues have random conformations. Fluorescence requenching experiments, in which liposomes serve as a mimic of the bacterial membranes, result in fluorophore leakage that is consistent with a membrane thinning or transient pore formation mechanism. NMR titration studies of the peptide-liposome interaction reveal that the peptide is in fast exchange with the liposome, consistent with the fluorescent studies. These data indicate that full length NA-CATH possesses a helical segment and unstructured C-terminal tail that disrupts the bilayer to induce leakage and lysing. PMID:26205847

  3. Application of liposomal technologies for delivery of platinum analogs in oncology

    Directory of Open Access Journals (Sweden)

    Liu D

    2013-08-01

    Full Text Available Demin Liu1, Chunbai He1, Andrew Z Wang2, Wenbin Lin1 1Department of Chemistry, University of Chicago, Chicago, IL, USA; 2Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA Abstract: Platinum-based chemotherapy, such as cisplatin, oxaliplatin, and carboplatin, is one of the most widely utilized classes of cancer therapeutics. While highly effective, the clinical applications of platinum-based drugs are limited by their toxicity profiles as well as suboptimal pharmacokinetic properties. Therefore, one of the key research areas in oncology has been to develop novel platinum analog drugs and engineer new platinum drug formulations to improve the therapeutic ratio further. Such efforts have led to the development of platinum analogs including nedaplatin, heptaplatin, and lobaplatin. Moreover, reformulating platinum drugs using liposomes has resulted in the development of L-NDPP (Aroplatin™, SPI-77, Lipoplatin™, Lipoxal™, and LiPlaCis®. Liposomes possess several attractive biological activities, including biocompatibility, high drug loading, and improved pharmacokinetics, that are well suited for platinum drug delivery. In this review, we discuss the various platinum drugs and their delivery using liposome-based drug delivery vehicles. We compare and contrast the different liposome platforms as well as speculate on the future of platinum drug delivery research. Keywords: liposome, platinum analog, drug delivery, cancer

  4. Liposomes incorporating cyclodextrin-drug inclusion complexes: Current state of knowledge.

    Science.gov (United States)

    Gharib, Riham; Greige-Gerges, Hélène; Fourmentin, Sophie; Charcosset, Catherine; Auezova, Lizette

    2015-09-20

    Cyclodextrins (CDs) are cyclic oligosaccharides, consisting of glucopyranose units, which are able to form host-guest inclusion complexes with lipophilic molecules. The ability of CD to increase drug solubility may be used to increase drug entrapment in the aqueous compartment of liposomes and liposomes can protect CD/drug inclusion complexes until drug release. Liposomes are phospholipid vesicles composed of lipid bilayers enclosing one or more aqueous compartments. They have been widely used as safe and effective carriers for both hydrophilic and lipophilic drugs. However, lipophilic drugs incorporated in the membrane bilayers can be rapidly released, which limits the effectiveness of this drug delivery system. The coupling of both delivery systems by encapsulating CD/drug inclusion complex into liposomes is proposed to circumvent the drawbacks of each separate system. Here, we review the literature regarding the encapsulation of CD/drug inclusion complex into conventional, deformable and double loaded liposomes. The review highlights the characteristics of these systems and presents the advantages and disadvantages of each one. PMID:26050903

  5. In Vitro and in Vivo Activities of Ticarcillin-Loaded Nanoliposomes with Different Surface Charges Against Pseudomonas Aeruginosa (ATCC 29248

    Directory of Open Access Journals (Sweden)

    Zohreh Faezizadeh

    2012-10-01

    Full Text Available Background:Pseudomonas aeruginosa exhibits multiple antibiotic resistance mechanisms. Different studies have shown that entrapment of antibiotics into liposomes could increase their anti-Pseudomonas activity. The objectives of this study were to prepare ticarcillin loadednanoliposomes with variable surface charges and evaluate their in vitro and in vivo efficacies against Pseudomonas aeruginosa (ATCC 29248.Methods:Ticarcillin-loaded nanoliposomes with positive, negative and neutral surface charges were prepared by extrusion method. Ticarcillin encapsulation efficacies for different formulationswere measured by HPLC method. Minimum inhibitory concentration (MIC of ticarcillin nanoliposomal forms against strain ATCC 29248 were determined by broth dilution method.The killing rate of Pseudomonas aeruginosa was exposed to various concentrations of ticarcillin in free and nanoliposomal forms were analyzed. Ultimately, in vivo therapeutic efficacy of nanoliposomes in burned mice skin infected with strain ATCC 29248 was investigated.Results:The encapsulation efficacies for ticarcillin-loaded cationic nanoliposomes were significantly higher (76%±0.17 than those of neutral (55%±0.14 and anionic (43%±0.14 nanoliposomes.The MIC of free, cationic, neutral and anionic nanoliposomal forms of ticarcillin against ATCC 29248 were to 24, 3, 6 and 48 mg/L, respectively. The killing rates of ticarcillinloaded cationic nanoliposomes were higher than those of free and other drug formulations.Treatment by ticarcillin-loaded nanoliposomes with positive, neutral and negative surface charges resulted in almost 100, 60 and 20% survival rates, respectively.Conclusion:Our data suggested that cationic ticarcillin-loaded nanoliposomes because of high effectiveness would be a good choice to treatment of Pseudomonas aeruginosa infections.

  6. 整合素受体和细胞穿膜肽共修饰紫杉醇脂质体抑制食管癌Ec9706细胞的研究%The Inhibition Effect of RGD and R8 Co-modified Paclitaxel Loaded Liposome on the Esophagus Carcinoma EC9706 Cells

    Institute of Scientific and Technical Information of China (English)

    吕行; 印滇

    2014-01-01

    目的:制备整合素受体RGD和细胞穿膜肽R8共修饰载紫杉醇( PTX)脂质体( RGD/R8-LP-PTX),对其理化性质进行表征,并观察脂质体与食管癌Ec9706细胞的亲和力和增殖抑制作用。方法:采用薄膜分散法制备RGD/R8-LP-PTX,观察脂质体的粒径,电位以及包封率;通过定量细胞摄取实验观察食管癌Ec9706细胞对RGD/R8-LP的摄取效率以及对脂质体摄取的影响因素。定性共聚焦实验观察肿瘤细胞对脂质体的摄取。 MTT实验观察RGD/R8-LP-PTX对食管癌Ec9706细胞的细胞毒性;构建食管癌Ec9706细胞肿瘤球模型,观察脂质体对肿瘤球的生长抑制能力。结果: RGD/R8-LP-PTX的粒径在124.8±9.4 nm,电位为21.35±3.55 mV。食管癌Ec9706细胞对RGD/R8-LP的摄取以及 RGD/R8-LP-PTX 对食管癌 Ec9706细胞的增殖抑制率具有时间依赖性;食管癌Ec9706细胞对RGD/R8-LP的摄取效率显著高于R8-LP、RGD-LP和LP,差异有统计学意义(P<0.01);在给药48 h后,R8-LP-PTX、RGD-LP-PTX和LP-PTX的细胞存活率分别是RGD/R8-LP-PTX组的1.6倍、1.7倍和2.2倍,差异有统计学意义(P<0.01)。给药7天后,生理盐水组肿瘤球持续生长,体积增大1.48倍,LP-PTX组肿瘤球体积增大到原体积的1.12倍, RGD/R8-LP-PTX组、R8-LP-PTX组和 RGD-LP-PTX组肿瘤球体积减小到原体积的36%、59%和64%,差异具有统计学意义(P<0.01)。结论:整合素受体RGD和细胞穿膜肽R8共修饰载紫杉醇(PTX)脂质体能够有效穿透肿瘤细胞膜进入肿瘤细胞,是一种有效的食管癌化疗靶向给药系统。%Objective: To prepare RGD and R8 co-modified paclitaxel loaded liposome(RGD/R8-LP-PTX)for EC9706 cells’ treatment. Methods: The co-modified liposome was prepared by film-ultrasonic method. The appearance, particle size,Zeta potential were evaluated. The cellular uptake by EC9706 cells in vitro was used to evaluate the targeting efficiency. The anti-proliferation efficiency of

  7. Cyclic RGD peptide-modified liposomal drug delivery system: enhanced cellular uptake in vitro and improved pharmacokinetics in rats

    Directory of Open Access Journals (Sweden)

    Chen Z

    2012-07-01

    Full Text Available Zhongya Chen,1,2 Jiaxin Deng,1,2 Yan Zhao,1,2 Tao Tao1,21National Pharmaceutical Engineering Research Center, 2Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of ChinaBackground: Integrins αvβ3 and αvβ5, both of which specifically recognize the Arg-Gly-Asp (RGD motif, are overexpressed on many solid tumors and in tumor neovasculature. Thus, coupling the RGD motif to the liposomal surface for achieving active targeting can be a promising strategy for the treatment of tumors.Methods: Cyclo(Arg-Gly-Asp-D-Phe-Cys (cRGD was covalently coupled with the liposomal membrane surface, followed by coating with poly(ethylene glycol (PEG using the post-insertion technique. The coupling efficiency of cRGD was determined. Doxorubicin as a model anticancer drug was loaded into liposomes using an ammonium sulfate gradient method to investigate the encapsulation efficiency, cellular uptake by the integrin-overexpressing human glioma cell line U87MG in vitro, and pharmacokinetic properties in Sprague-Dawley rats.Results: cRGD was conjugated to the liposomal surface by a thiol-maleimide coupling reaction. The coupling efficiency reached 98%. The encapsulation efficiency of doxorubicin in liposomes was more than 98%. The flow cytometry test result showed that cRGD-modified liposomes (RGD-DXRL-PEG had higher cell uptake by U87MG cells, compared with nontargeted liposomes (DXRL-PEG. The cellular uptake was significantly inhibited in the presence of excess free cRGD. Both the targeted (t1/2 = 24.10 hours and non-targeted (t1/2 = 25.32 hours liposomes showed long circulating properties in rat plasma. The area under the curve of the targeted and nontargeted liposomes was 6.4-fold and 8.3-fold higher than that of doxorubicin solution, respectively.Conclusion: This study indicates preferential targeting and long circulating properties for cRGD-modified liposomes in vivo, which could be used as

  8. RGD peptide conjugated liposomal drug delivery system for enhance therapeutic efficacy in treating bone metastasis from prostate cancer.

    Science.gov (United States)

    Wang, Fangfang; Chen, Lei; Zhang, Rui; Chen, Zhongping; Zhu, Li

    2014-12-28

    Targeting αvβ3 integrin is particularly promising for the treatment of bone metastases by targeting integrin-rich tumor cells and by inhibiting integrin-involved bone metastases. In this work, a liposomal drug delivery system conjugated with cyclic arginine-glycine-aspartic acid-tyrosine-lysine peptide (cRGDyk) as αvβ3 integrin ligand was thus developed to improve therapeutic efficacy in a mice model of bone metastasis from prostate cancer. The resultant liposomes were characterized in terms of size, morphology, zeta potential, stability, drug encapsulation percentage and loading efficiency, and drug release. Compared with free cisplatin and cRGDyk-free liposomes, cRGDyk conjugated liposomes showed significantly higher cellular uptake and higher cytotoxicity of loaded cisplatin, as evidenced by in vitro cell experiments. In vivo results revealed that free cisplatin and free cRGDyk could relieve tumor-induced pain but had no contributions to tumor regression and overall survival improvement. cRGDyk-free liposomal drug system with prolonged blood circulation time could accumulated in the tumor sites in the bone through enhanced permeability and retention (EPR) effects and however, did not exhibit desirable therapeutic efficacy superior to free cisplatin and free cRGDyk. This strongly suggested that ERP effects were not effective in treating metastases. By taking advantages of targeted drug delivery and synergistic antitumor activity of cRGDyk and loaded cisplatin, cRGDyk conjugated liposomal drug system could inhibit osteoclastic and osteoblastic bone lesions, relieve pain, and improve overall survival. Inspired by their enhanced therapeutic efficacy and low organ toxicity, cRGDyk conjugated liposomes could serve as an effective drug system for targeted and synergistic therapy of bone metastases. PMID:25456829

  9. Preparation, characterization and in vitro evaluation of sterically stabilized liposome containing a naphthalenediimide derivative as anticancer agent.

    Science.gov (United States)

    Parise, Amelia; Milelli, Andrea; Tumiatti, Vincenzo; Minarini, Anna; Neviani, Paolo; Zuccari, Guendalina

    2015-01-01

    The aim of this study was to incorporate a new naphthalenediimide derivative (AN169) with a promising anticancer activity into pegylated liposomes to an extent that allows its in vitro and in vivo testing without use of toxic solvent. AN169-loaded liposomes were prepared using the thin-film hydration method and characterized for size, polydispersity index, drug content and drug release. We examined their lyophilization ability in the presence of cryoprotectants (trehalose, sucrose and lysine) and the long-term stability of the lyophilized products stored at 4 °C for 3 and 6 months by particle size changes and drug leakage. AN169 was successfully loaded into liposomes with an entrapment efficiency of 87.3 ± 2.5%. The hydrodynamic diameter of these liposomes after sonication was ∼ 145 nm with a high degree of monodispersity. Trehalose was found to be superior to the other lyoprotectants. In particular, trehalose 1:10 lipid:cryoprotectant molar ratio may provide stable lyophilized liposomes with the conservation of physicochemical properties upon freeze-drying and long-term storage conditions. We also assessed their in vitro antitumor activity in human cancer cell lines (HTLA-230 neuroblastoma, Mel 3.0 melanoma, OVCAR-3 ovarian carcinoma and SV620 prostate cancer cells). However, only after 72 h incubation, loaded liposomes showed almost the same IC50 as free AN169. In conclusion, we developed a stable lyophilized liposomal formulation for intravenous administration of AN169 as anticancer drug, with the advantage of avoiding the use of potentially toxic solubilizing agents for future in vivo experiments. PMID:24286206

  10. Quantifying the effects of melittin on liposomes.

    Science.gov (United States)

    Popplewell, J F; Swann, M J; Freeman, N J; McDonnell, C; Ford, R C

    2007-01-01

    Melittin, the soluble peptide of bee venom, has been demonstrated to induce lysis of phospholipid liposomes. We have investigated the dependence of the lytic activity of melittin on lipid composition. The lysis of liposomes, measured by following their mass and dimensions when immobilised on a solid substrate, was close to zero when the negatively charged lipids phosphatidyl glycerol or phosphatidyl serine were used as the phospholipid component of the liposome. Whilst there was significant binding of melittin to the liposomes, there was little net change in their diameter with melittin binding reversed upon salt injection. For the zwitterionic phosphatidyl choline the lytic ability of melittin is dependent on the degree of acyl chain unsaturation, with melittin able to induce lysis of liposomes in the liquid crystalline state, whilst those in the gel state showed strong resistance to lysis. By directly measuring the dimensions and mass changes of liposomes on exposure to melittin using Dual Polarisation Interferometry, rather than following the florescence of entrapped dyes we attained further information about the initial stages of melittin binding to liposomes. PMID:17092481

  11. PREPARATION, CHARACTERIZATION AND EVALUATION OF HEPATOPROTECTIVE ACTIVITY OF AN INTRAVENOUS LIPOSOMAL FORMULATION OF BIS-DEMETHOXY CURCUMIN ANALOGUE (BDMCA

    Directory of Open Access Journals (Sweden)

    PREPARATION, CHARACTERIZATION AND EVALUATION OF HEPATOPROTECTIVE ACTIVITY OF AN INTRAVENOUS LIPOSOMAL FORMULATION OF BIS-DEMETHOXY CURCUMIN ANALOGUE (BDMCA

    2009-12-01

    Full Text Available The aim of study was to prepare small unilamellar vesicles (SUVs incorporating BDMCA that can injected by intravenousroute and further, evaluate hepatoprotective activity of the formulation. SUV liposomes were prepared using thin filmhydration followed by sonication method. Soya lecithin was used as lipid and stearyl amine was used as cationic chargeinducer. In the preparation of liposomes, process and formulation parameters were standardized. After preparation SUVswere characterized for physicochemical properties, particle size, zetapotential, percent drug entrapment, in vitro drugrelease and the drug-polymer interaction. The sustenance of drug release into the plasma after intravenous BDMCA SUVadministration was determined. Hepatoprotective activity was evaluated in CCl4 treated rats. The liposomal formulationswere successfully prepared using thin film hydration followed by sonication method. The desired encapsulation wasachieved by increase in the area of the lipid film formed. The size of SUVs obtained was 327 nm. FTIR results indicate therewas no interaction between lipid and drug. In vitro release data showed that the release was sustained for 10 days in vitroand could be described as diffusion-controlled. The liposomal formulations were able to sustain the release of drug in vivoalso. Liposomal formulations showed better hepatoprotective activity to the drug compared to its solution form.

  12. Liposome imaging agents in personalized medicine

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa; Hansen, Anders Elias; Gabizon, Alberto;

    2012-01-01

    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...... arena where we 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 of radiolabeled liposomes for imaging as a tool in personalized medicine....

  13. Studies on liposomes with Chlorophyll for monitoring the electromagnetic influence at molecular level

    International Nuclear Information System (INIS)

    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

  14. Elucidating the mechanisms of protein antigen adsorption to the CAF/NAF liposomal vaccine adjuvant systems

    DEFF Research Database (Denmark)

    Hamborg, Mette; Rose, Fabrice; Jorgensen, Lene;

    2014-01-01

    The reverse vaccinology approach has recently resulted in the identification of promising protein antigens, which in combination with appropriate adjuvants can stimulate customized, protective immune responses. Although antigen adsorption to adjuvants influences vaccine efficacy and safety, little...... attractive interaction with the zwitterionic liposomes. In contrast, the net cationic lysozyme showed very little interaction with either types of liposome. Adsorption of α-lactalbumin altered its tertiary structure, affected lipid membrane packing below and above the phase transition temperature, and...... way vaccine antigens are presented to antigen-presenting cells, and may play an important role for the efficacy of the vaccine-induced immune response. These studies thus exemplify the importance of characterizing the molecular interactions between the vaccine antigen and adjuvant along with...

  15. Enhanced anticancer potency using an acid-responsive ZnO-incorporated liposomal drug-delivery system

    Science.gov (United States)

    Tripathy, Nirmalya; Ahmad, Rafiq; Ko, Hyun Ah; Khang, Gilson; Hahn, Yoon-Bong

    2015-02-01

    The development of stimuli-responsive nanocarriers is becoming important in chemotherapy. Liposomes, with an appropriate triggering mechanism, can efficiently deliver their encapsulated cargo in a controlled manner. We explored the use of acid-sensitive zinc oxide nanoparticles (ZNPs) as modulators of the responsive properties of liposomes. Nanocomplexes formed by the incorporation of ZNPs in liposomes (ZNP-liposomes) were designed to demonstrate the pH-responsive release of a drug (daunorubicin) without premature drug leakage and with the maintenance of the relevant therapeutic concentrations. The nanocomplexes were spherical in shape with a narrow size distribution and showed a high drug-encapsulating efficiency. Under acidic conditions, the ZNP-liposome nanocomplexes released the loaded drug more rapidly than bare liposomes. Using flow cytometry, confocal microscopy and an MTT assay, we demonstrated that these nanocomplexes were readily taken up by cancer cells, resulting in significantly enhanced cytotoxicity. On exposure to the acidic conditions inside cancer cells, the ZNPs rapidly decomposed, releasing the entrapped drug molecules from the ZNP-liposome nanocomplexes, producing widespread cytotoxic effects. The incorporated ZNPs were multimodal in that they not only resulted in a pH-responsive drug-delivery system, but they also had a synergistic chemo-photodynamic anticancer action. This design provides a significant step towards the development of multimodal liposome structures.The development of stimuli-responsive nanocarriers is becoming important in chemotherapy. Liposomes, with an appropriate triggering mechanism, can efficiently deliver their encapsulated cargo in a controlled manner. We explored the use of acid-sensitive zinc oxide nanoparticles (ZNPs) as modulators of the responsive properties of liposomes. Nanocomplexes formed by the incorporation of ZNPs in liposomes (ZNP-liposomes) were designed to demonstrate the pH-responsive release of a drug

  16. Enhanced Cellular Delivery and Biocompatibility of a Small Layered Double Hydroxide–Liposome Composite System

    Directory of Open Access Journals (Sweden)

    Haiyan Dong

    2014-11-01

    Full Text Available The various classes of gene delivery vectors possess distinct advantages and disadvantages, each of which impacts on cargo loading, delivery and, ultimately, its function. With this in mind, herein we report on a small layered double hydroxide (sLDH–liposome composite system, drawing upon the salient features of LDH and liposome classes of vectors, while avoiding their inherent shortfalls when used independently. sLDH–liposome composites were prepared by the hydration of freeze-dried matrix method. These composite systems, with a Z-average size of ≈200 nm, exhibited low cytotoxicity and demonstrated good suspension stability, both in water and cell culture medium after rehydration. Our studies demonstrate that short dsDNAs/ssDNAs were completely bound and protected in the composite system at an sLDH:DNA mass ratio of 20:1, regardless of the approach to DNA loading. This composite system delivered DNA to HCT-116 cells with ≈3-fold greater efficiency, when compared to sLDH alone. Our findings point towards the sLDH-liposome composite system being an effective and biocompatible gene delivery system.

  17. LIPOSOME AS A POTENTIAL DRUG DELIVERY SYSTEM: A REVIEW

    Directory of Open Access Journals (Sweden)

    Dash Tapaswi Rani

    2013-01-01

    Full Text Available Liposomes are microscopic phospholipid vescicles made of lipid bilayer which are the drug carrier for improving the delivery of therapeutic agents. Research on liposome technology has progressed from conventional vesicles (“first-generation liposomes” to “second-generation liposomes”, in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modified surfaces have also been developed using several molecules, such as glycolipids or sialic acid. A significant step in the development of long-circulating liposomes came with inclusion of the synthetic polymer poly-(ethylene glycol (PEG in liposome composition. Due to advancement in liposomal technology a number of liposomal formulations are available in market for clinical use, with gene delivery and cancer therapy and some formulations are under clinical trial. Reformulation of drugs in liposomes has provided an opportunity to enhance the therapeutic indices of various agents mainly through alteration in their biodistribution. This review discusses the basic principles of liposome structures and preparations, evaluation parameters of liposomal formulation, pharmacokinetics of liposomes and liposome-encapsulated drugs, the potential applications of liposomes in drug delivery with examples of formulations approved for clinical use, and the problems associated with further exploitation of this drug delivery system.

  18. Liposomes containing glycocholate as potential oral insulin delivery systems: preparation, in vitro characterization, and improved protection against enzymatic degradation

    Directory of Open Access Journals (Sweden)

    Niu M

    2011-06-01

    Full Text Available Mengmeng Niu1, Yi Lu1, Lars Hovgaard2, Wei Wu11School of Pharmacy, Fudan University, Shanghai, People's Republic of China; 2Oral Formulation Development, Novo Nordisk A/S, Maalov, DenmarkBackground: Oral delivery of insulin is challenging and must overcome the barriers of gastric and enzymatic degradation as well as low permeation across the intestinal epithelium. The present study aimed to develop a liposomal delivery system containing glycocholate as an enzyme inhibitor and permeation enhancer for oral insulin delivery.Methods: Liposomes containing sodium glycocholate were prepared by a reversed-phase evaporation method followed by homogenization. The particle size and entrapment efficiency of recombinant human insulin (rhINS-loaded sodium glycocholate liposomes can be easily adjusted by tuning the homogenization parameters, phospholipid:sodium glycocholate ratio, insulin:phospholipid ratio, water:ether volume ratio, interior water phase pH, and the hydration buffer pH.Results: The optimal formulation showed an insulin entrapment efficiency of 30% ± 2% and a particle size of 154 ± 18 nm. A conformational study by circular dichroism spectroscopy and a bioactivity study confirmed the preserved integrity of rhINS against preparative stress. Transmission electron micrographs revealed a nearly spherical and deformed structure with discernable lamella for sodium glycocholate liposomes. Sodium glycocholate liposomes showed better protection of insulin against enzymatic degradation by pepsin, trypsin, and a-chymotrypsin than liposomes containing the bile salt counterparts of sodium taurocholate and sodium deoxycholate.Conclusion: Sodium glycocholate liposomes showed promising in vitro characteristics and have the potential to be able to deliver insulin orally.Keywords: liposomes, glycocholate, insulin, enzymatic degradation, oral

  19. Preparation, biodistribution and neurotoxicity of liposomal cisplatin following convection enhanced delivery in normal and F98 glioma bearing rats.

    Directory of Open Access Journals (Sweden)

    Tianyao Huo

    Full Text Available The purpose of this study was to evaluate two novel liposomal formulations of cisplatin as potential therapeutic agents for treatment of the F98 rat glioma. The first was a commercially produced agent, Lipoplatin™, which currently is in a Phase III clinical trial for treatment of non-small cell lung cancer (NSCLC. The second, produced in our laboratory, was based on the ability of cisplatin to form coordination complexes with lipid cholesteryl hemisuccinate (CHEMS. The in vitro tumoricidal activity of the former previously has been described in detail by other investigators. The CHEMS liposomal formulation had a Pt loading efficiency of 25% and showed more potent in vitro cytotoxicity against F98 glioma cells than free cisplatin at 24 h. In vivo CHEMS liposomes showed high retention at 24 h after intracerebral (i.c. convection enhanced delivery (CED to F98 glioma bearing rats. Neurotoxicologic studies were carried out in non-tumor bearing Fischer rats following i.c. CED of Lipoplatin™ or CHEMS liposomes or their "hollow" counterparts. Unexpectedly, Lipoplatin™ was highly neurotoxic when given i.c. by CED and resulted in death immediately following or within a few days after administration. Similarly "hollow" Lipoplatin™ liposomes showed similar neurotoxicity indicating that this was due to the liposomes themselves rather than the cisplatin. This was particularly surprising since Lipoplatin™ has been well tolerated when administered intravenously. In contrast, CHEMS liposomes and their "hollow" counterparts were clinically well tolerated. However, a variety of dose dependent neuropathologic changes from none to severe were seen at either 10 or 14 d following their administration. These findings suggest that further refinements in the design and formulation of cisplatin containing liposomes will be required before they can be administered i.c. by CED for the treatment of brain tumors and that a formulation that may be safe when given

  20. Liposomes as delivery systems for antineoplastic drugs

    Science.gov (United States)

    Medina, Luis Alberto

    2014-11-01

    Liposome drug formulations are defined as pharmaceutical products containing active drug substances encapsulated within the lipid bilayer or in the interior aqueous space of the liposomes. The main importance of this drug delivery system is based on its drastic reduction in systemic dose and concomitant systemic toxicity that in comparison with the free drug, results in an improvement of patient compliance and in a more effective treatment. There are several therapeutic drugs that are potential candidates to be encapsulated into liposomes; particular interest has been focused in therapeutic and antineoplastic drugs, which are characterized for its low therapeutic index and high systemic toxicity. The use of liposomes as drug carriers has been extensively justified and the importance of the development of different formulations or techniques to encapsulate therapeutic drugs has an enormous value in benefit of patients affected by neoplastic diseases.

  1. Liposomal Simvastatin Attenuates Neointimal Hyperplasia in Rats

    OpenAIRE

    Afergan, Eyal; Ben David, Meital; Epstein, Hila; Koroukhov, Nickolay; Gilhar, Dalia; Rohekar, Keren; Danenberg, Haim D.; Golomb, Gershon

    2010-01-01

    Monocytes, macrophages, and inflammation play a key role in the process of neointimal proliferation and restenosis. The present study evaluated whether systemic and transient depletion of monocytes could be obtained by a single intravenous (IV) injection of simvastatin liposomes, for the inhibition of neointima formation. Balloon-injured carotid artery rats (n = 30) were randomly assigned to treatment groups of free simvastatin, simvastatin in liposomes (3 mg/kg), and saline (control). Stenos...

  2. PREPARATION OF LIPOSOMES CONTAINING WHEY PROTEINS

    Directory of Open Access Journals (Sweden)

    A. Suha Yalçın

    2010-01-01

    Full Text Available Aim: In recent years, it has been shown that whey and its components have a number of health-promoting effects. We aimed to isolate fractions containing whey proteins using chromatography and then to prepare antioxidant liposomes in order to obtain a gel suitable for cosmetic preparations.Methods: Fractionation of whey proteins was achieved by extraction, filtration and centrifugation followed by liquid chromatography. The antioxidant activities of the fractions was determined by their copper ion reducing capacity. Gel electrophoresis was used to analyze the proteins. Liposomes were made by the thin film hydration method.Results and Conclusion: Using Sephadex G-50 chromatography, two fractions were obtained. The first fraction contained major whey proteins, while the second fraction had small peptides. We have then determined the antioxidant activities of these fractions. The first fraction had the highest antioxidant activity. We prepared liposomes containing whey protein fractions and analyzed their sizes. Then, we investigated the liposome structures under a light microscope, electron microscope and atomic force microscope. Finally, we prepared a cosmetic formula from liposomes containing the whey fractions. We believe that preparing antioxidant liposomes containing whey proteins will be an important contribution to the cosmetic formulas for dermal applications.

  3. 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.

  4. 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.

  5. Effect of surface-potential modulators on the opening of lipid pores in liposomal and mitochondrial inner membranes induced by palmitate and calcium ions.

    Science.gov (United States)

    Belosludtsev, Konstantin N; Belosludtseva, Natalia V; Agafonov, Alexey V; Penkov, Nikita V; Samartsev, Victor N; Lemasters, John J; Mironova, Galina D

    2015-10-01

    The effect of surface-potential modulators on palmitate/Ca2+-induced formation of lipid pores was studied in liposomal and inner mitochondrial membranes. Pore formation was monitored by sulforhodamine B release from liposomes and swelling of mitochondria. ζ-potential in liposomes was determined from electrophoretic mobility. Replacement of sucrose as the osmotic agent with KCl decreased negative ζ-potential in liposomes and increased resistance of both mitochondria and liposomes to the pore inducers, palmitic acid, and Ca2+. Micromolar Mg2+ also inhibited palmitate/Ca2+-induced permeabilization of liposomes. The rate of palmitate/Ca2+-induced, cyclosporin A-insensitive swelling of mitochondria increased 22% upon increasing pH from 7.0 to 7.8. At below the critical micelle concentration, the cationic detergent cetyltrimethylammonium bromide (10 μM) and the anionic surfactant sodium dodecylsulfate (10-50 μM) made the ζ-potential less and more negative, respectively, and inhibited and stimulated opening of mitochondrial palmitate/Ca2+-induced lipid pores. Taken together, the findings indicate that surface potential regulates palmitate/Ca2+-induced lipid pore opening. PMID:26014488

  6. Preliminary radiochemical and biological studies on the liposome encapsulated platinum-[125I]iodohistamine complex

    International Nuclear Information System (INIS)

    The platinum-iodohistamine complex with in vitro cytostatic activity toward colon and mammary cancer cells has been synthesised recently in our laboratory. The pharmacokinetics of radioactive complex analogues, labelled with I-131 and I-125, has been examined in murine model of spontaneous mammary adenocarcinoma. The present work is devoted to the examination of the potential use of liposomes as a carrier system for the radioactive platinum-[*I]iodohistamine complex in vivo. Encapsulations of the Pt-125I]iodohistamine were studied using a different molar ratio of the complex and liposomes with positive surface charge, as well as various incubation procedures. Biodistribution of the initial and the liposomal form of the complex were studied in C3H tumour-bearing mice with spontaneously developed and transplantable (16C) mammary adenocarcinoma. Comparative biodistribution studies in C3H/16C mice and in mice with spontaneously developed mammary tumour have shown that in the former model pharmacokinetics of the Pt-[125 I]iodohistamine complex is more predictable and more similar to that observed for cisplatin. Therefore, the transplantable tumour model is more advantageous for the complex and its liposomal form evaluation. In C3H/16C mice, significant differences in the biodistribution between the radioactive platinum complex and its liposomal form were observed. The concentration of the activity in blood after 2 h p.i.v. was two times lower for the encapsulated complex, and the uptake of the radioactivity by liver, spleen, and lungs was twice as high as that obtained for the free Pt-[125I]iodohistamine preparation. The radioactivity in tumour was almost constant for liposomal platinum complex (ca. 2% ID/g), although it was two times lower compared to the initial platinum complex. The results of the present study indicate that platinum-[*I]iodohistamine can be efficiently incorporated into cationic liposomes (c. 40%). However, the uptake of the encapsulated complex by

  7. Surface Charge Density Determines the Efficiency of Cationic Gemini Surfactant Based Lipofection

    Science.gov (United States)

    Ryhänen, Samppa J.; Säily, Matti J.; Paukku, Tommi; Borocci, Stefano; Mancini, Giovanna; Holopainen, Juha M.; Kinnunen, Paavo K. J.

    2003-01-01

    The efficiencies of the binary liposomes composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine and cationic gemini surfactant, (2S,3R)-2,3-dimethoxy-1,4-bis(N-hexadecyl-N,N-dimethylammonium)butane dibromide as transfection vectors, were measured using the enhanced green fluorescent protein coding plasmid and COS-1 cells. Strong correlation between the transfection efficiency and lipid stoichiometry was observed. Accordingly, liposomes with XSR−1 ≥ 0.50 conveyed the enhanced green fluorescent protein coding plasmid effectively into cells. The condensation of DNA by liposomes with XSR−1 > 0.50 was indicated by static light scattering and ethidium bromide intercalation assay, whereas differential scanning calorimetry and fluorescence anisotropy of diphenylhexatriene revealed stoichiometry dependent reorganization in the headgroup region of the liposome bilayer, in alignment with our previous Langmuir-balance study. Surface charge density and the organization of positive charges appear to determine the mode of interaction of DNA with (2S,3R)-2,3-dimethoxy-1,4-bis(N-hexadecyl-N,N-dimethylammonium)butane dibromide/1,2-dimyristoyl-sn-glycero-3-phosphocholine liposomes, only resulting in DNA condensation when XSR−1 > 0.50. Condensation of DNA in turn seems to be required for efficient transfection. PMID:12524311

  8. Effect of quaternization degree of N-trimethyl chitosan on in vitro properties of pyridostigmine bromide-loaded liposomes%N-三甲基壳聚糖的季铵化程度对溴吡斯的明包衣脂质体体外性质的影响

    Institute of Scientific and Technical Information of China (English)

    郑文钺; 何文

    2013-01-01

    目的 考察N-三甲基壳聚糖(TMC)的季铵化程度(DQ)对TMC包衣溴吡斯的明脂质体(PB-L)体外性质的影响.方法 逆向蒸发法制备PB-L,以DQ分别为20%、40%及60%的TMC(即TMC20、TMC40、TMC60)对其进行包覆.对其形态进行观察,测定其粒径、Zeta电位及包封率,并对其体外释药特性进行考察.结果 TMC包衣PB-L外观呈圆整球形,具有明显的包衣层;TMC包衣后,PB-L粒径增加,且随DQ的增大而增大;包衣后PB-L的Zeta电位由负转正,且随DQ的增大而增大;DQ对包封率无显著性影响,平均包封率为(61.73±1.27)%(n=3);与未包衣PB-L相比,TMC包衣PB-L缓释性更显著,且释药速度随DQ的增大而降低.结论 DQ对TMC包衣PB-L的体外性质具有显著的影响.%Objective To investigate the effect of quatemization degree( DQ) of N-trimethyl chitosan(TMC) on the in vitro properties of pyridostigmine bromide-loaded liposomes ( PB-L) . Methods The PB-L was prepared by reverse phase evaporation coated by TMC with various DQ(TMC20,TMC40 and TMC60) . The morphology, size, Zeta potential, entrapment efficiency and in vitro drug release of TMC-coated PB-L were compared. Results TMC-coated PB-L showed spherical morphology with notable coating layer. After coating,the size was increased and showed positive correlation with DQ. The Zeta potential changed from negative to positive after TMC coating and showed positive correlation with DQ as well. DQ showed no significant effect on the average entrapment efficiency with the average value of (61.73 ± 1. 27) %(n = 3). Compared with un-coated PB-L, the in vitro sustained release property was more significant after TMC coating and with the increase of DQ,the release rate was decreased. Conclusion The DQ of TMC exhibits significant effect on the in vitro properties of TMC-coated PB-L.

  9. LIPOSOMAL GEL AS OCULAR DELIVERY SYSTEM FOR DICLOFENAC SODIUM: IN- VITRO AND IN-VIVO STUDIES

    Directory of Open Access Journals (Sweden)

    O. A. Sammour , Md. A. Mahdy , Hanan M. Elnahas* and Ayman A. Mowafy

    2013-01-01

    Full Text Available The aim of this work is to formulate topically effective controlled release ophthalmic liposomal gel for targeting diclofenac sodium to the eye in an attempt to heal the inflamed tissue of ocular ulcerative area. Large unilamellar vesicles (LUVs and multilamellar vesicles (MLVs gel formulations composing of phosphatidylcholine (PC and cholesterol (CH in the molar ratios of (7:2; 7:4 and 7:7 with or without stearylamine (SA or dicetylphosphate (DP were prepared using reversed-phase evaporation and lipid film hydration methods respectively. The prepared liposomal systems were evaluated for their entrapment efficiency, morphological characters, physical stability, particle size and drug release rate .LUVs entrapped greater amount of drug than MLVs. Drug loading was increased by increasing CH content as well as by inclusion of SA into the lipid bilayer. Drug release rate showed an order of negatively > neutral > positively charged liposomes, which is the reverse of results of drug loading efficiency. Physical stability study indicated that 92.56%, 84.11%, 76.41% and 91.1%, 82.19% and 75.54% of diclofenac sodium was retained in positive, negative, and neutral MLVs and LUVs respectively after storing for 120 days at refrigeration temperature. The in vivo anti-inflammatory activity was evaluated using a thermal technique , results showed that the percentage of healed ulcers were 12.5%, 35%, 67.5%, 82.5%, 85%, 87.5% and 95% for negative control, positive control, 0.5% carbopol 934 gel, LUVs liposomes suspension, MLVs liposomes suspension, LUVs and MLVs gels, respectively.

  10. Improved stability and skin permeability of sodium hyaluronate-chitosan multilayered liposomes by Layer-by-Layer electrostatic deposition for quercetin delivery.

    Science.gov (United States)

    Jeon, Soha; Yoo, Cha Young; Park, Soo Nam

    2015-05-01

    Layer-by-Layer (LbL) technology, based on the electrostatic interaction of polyelectrolytes, is used to improve the stability of drug delivery systems. In the present study, we developed multilayered liposomes with up to 10 alternating layers based on LbL deposition of hyaluronate-chitosan for transdermal delivery. Dihexadecyl phosphate was used to provide liposomes with a negative charge; the liposomes were subsequently coated with cationic chitosan (CH) followed by anionic sodium hyaluronate (HA). The resulting particles had a cumulative size of 528.28±29.22nm and an alternative change in zeta potential. Differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) revealed that the multilayered liposomes formed a spherical polyelectrolyte complex (PEC) after deposition. Observations in size distribution after 1 week found that the particles coated with even layers of polyelectrolytes, hyaluronate and chitosan (HA-CH), were more stable than the odd layers. Membrane stability in the presence of the surfactant Triton X-100 increased with an increase in bilayers as compared to uncoated liposomes. An increase in the number of bilayers deposited on the liposomal surface resulted in a sustained release of quercetin, with release kinetics that fit the Korsmeyer-Peppas model. In an in vitro skin permeation study, negatively charged (HA-CH)-L and positively charged CH-L were observed to have similar skin permeability, which were superior to uncoated liposomes. These results indicate that multilayered liposomes properly coated with polyelectrolytes of HA and CH by electrostatic interaction improve stability and can also function as potential drug delivery system for the transdermal delivery of the hydrophobic antioxidant quercetin. PMID:25819360

  11. Urinary microalbumin measurement using a homogeneous liposomal immunoassay.

    Science.gov (United States)

    Frost, S J; Chakraborty, J; Firth, G B

    1996-08-14

    A homogeneous colorimetric immunoassay which has been developed for urinary microalbumin utilizes complement-mediated immunolysis of liposomes containing the dye, sulphorhodamine B. Unlike a previously described model complement-mediated liposomal assay for serum albumin (Frost et al., 1994) which was competitive, this assay uses a sandwich-type format and Fab' (antialbumin)-coated liposomes to increase the assay sensitivity. The liposomal assay, performed using a Cobas Bio analyser (Roche, Welwyn Garden City, UK), gave an acceptable correlation with a radioimmunoassay (NETRIA, London, UK): r = 0.94; y (liposomal assay) = 1.09 x (radioimmunoassay) - 1.54 mg/1. The imprecisions of the assays were similar and matrix effects due to the use of urine samples were determined to be acceptably small. The assay demonstrates the advantage of using Fab'-coated liposomes in sandwich-type liposomal immunoassays over liposomes coated with intact antibody, which failed to elicit complement-mediated immunolysis. PMID:8765163

  12. Effect of diglucosamine on the entrapment of protein into liposomes.

    Science.gov (United States)

    Murakami, S; Ono, T; Sakai, S; Ijima, H; Kawakami, K

    2006-01-01

    Liposomes, which had entrapped bovine serum albumin (BSA), were modified with diglucosamine by two methods. The liposome was prepared by a freeze-thawing method in the presence of the disaccharide, or the disaccharide was added to the liposome prepared in advance without it. To examine the effects of diglucosamine, the morphology, mean particle size, and zeta potential of both liposomes were compared with those of BSA-entrapping liposome prepared without the disaccharide. Diglucosamine caused no remarkable change in shape and no aggregation of the liposome. The presence of the disaccharide was confirmed on the surfaces of modified liposomes, and the entrapment of BSA into the liposomes was increased by the disaccharide. The entrapment behavior was affected by the way the disaccharide was added, and the difference in the way the BSA was entrapped was also indicated. PMID:16753965

  13. Anaphylaxis to Pegylated Liposomal Doxorubicin: A Case Report

    Science.gov (United States)

    Sharma, LR; Subedi, A; Shah, BK

    2014-01-01

    Liposomal doxorubicin is used for the treatment of various cancers like epithelial ovarian cancers, multiple myeloma and sarcomas. We report the first case of anaphylaxis to pegylated liposomal doxorubicin. PMID:25429486

  14. Anaphylaxis to Pegylated Liposomal Doxorubicin: A Case Report

    OpenAIRE

    Sharma, LR; A. Subedi; Shah, BK

    2014-01-01

    Liposomal doxorubicin is used for the treatment of various cancers like epithelial ovarian cancers, multiple myeloma and sarcomas. We report the first case of anaphylaxis to pegylated liposomal doxorubicin.

  15. Enhanced Transdermal Delivery of Diclofenac Sodium via Conventional Liposomes, Ethosomes, and Transfersomes

    OpenAIRE

    Saeed Ghanbarzadeh; Sanam Arami

    2013-01-01

    The aim of this study was to improve the transdermal permeation of Diclofenac sodium, a poorly water-soluble drug, employing conventional liposomes, ethosomes, and transfersomes. The prepared formulations had been characterized for the loaded drug amount and vesicle size. The prepared vesicular systems were incorporated into 1% Carbopol 914 gel, and a survey of in vitro drug release and drug retention into rat skin has been done on them using a modified Franz diffusion cell. The cumulative am...

  16. Generation of superparamagnetic liposomes revealed as highly efficient MRI contrast agents for in vivo imaging.

    Science.gov (United States)

    Martina, Marie-Sophie; Fortin, Jean-Paul; Ménager, Christine; Clément, Olivier; Barratt, Gillian; Grabielle-Madelmont, Cécile; Gazeau, Florence; Cabuil, Valérie; Lesieur, Sylviane

    2005-08-01

    Maghemite (gamma-Fe2O3) nanocrystals stable at neutral pH and in isotonic aqueous media were synthesized and encapsulated within large unilamellar vesicles of egg phosphatidylcholine (EPC) and distearoyl-SN-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE-PEG(2000), 5 mol %), formed by film hydration coupled with sequential extrusion. The nonentrapped particles were removed by flash gel exclusion chromatography. The magnetic-fluid-loaded liposomes (MFLs) were homogeneous in size (195 +/- 33 hydrodynamic diameters from quasi-elastic light scattering). Iron loading was varied from 35 up to 167 Fe(III)/lipid mol %. Physical and superparamagnetic characteristics of the iron oxide particles were preserved after liposome encapsulation as shown by cryogenic transmission electron microscopy and magnetization curve recording. In biological media, MFLs were highly stable and avoided ferrofluid flocculation while being nontoxic toward the J774 macrophage cell line. Moreover, steric stabilization ensured by PEG-surface-grafting significantly reduced liposome association with the macrophages. The ratios of the transversal (r2) and longitudinal (r1) magnetic resonance (MR) relaxivities of water protons in MFL dispersions (6 < r2/r1 < 18) ranked them among the best T2 contrast agents, the higher iron loading the better the T2 contrast enhancement. Magnetophoresis demonstrated the possible guidance of MFLs by applying a magnetic field gradient. Mouse MR imaging assessed MFLs efficiency as contrast agents in vivo: MR angiography performed 24 h after intravenous injection of the contrast agent provided the first direct evidence of the stealthiness of PEG-ylated magnetic-fluid-loaded liposomes. PMID:16045355

  17. Liposomes as vehicles for water insoluble platinum-based potential drug

    DEFF Research Database (Denmark)

    Kaluđerović, Goran N; Dietrich, Andrea; Kommera, Harish;

    2012-01-01

    Formulation of liposome delivery system loaded with water insoluble 2-(4-(tetrahydro-2H-pyran-2-yloxy)-undecyl)-propane-1,3-diamminedichloroplatinum(II), LipoTHP-C11 was carried out. The particle size distributions were determined by dynamic light scattering and asymmetrical flow field-flow fract......, toxicity against normal fibroblasts was examined. LipoTHP-C11 may be used as an attractive candidate for further assessment in vivo as antitumor agent....

  18. Stimulation of cation transport in mitochondria by gramicidin and truncated derivatives

    International Nuclear Information System (INIS)

    Gramicidin and the truncated derivatives desformylgramicidin (desfor) and des(formylvalyl)gramicidin (desval) stimulate monovalent cation transport in rat liver mitochondria. Cation fluxes were compared indirectly from the effect of cations on the membrane potential at steady state (state 4) or from the associated stimulation of electron transport. Rb+ transport was measured directly from the uptake of 86Rb. The truncated gramicidins show enhanced selectivity for K+ and Rb+ when compared to gramicidin. Moreover, the pattern of selectivity within the alkali cation series is altered. The cation fluxes through the truncated derivatives are more strongly dependent on the cation concentration. The presence of high concentrations of permeating cation enhances the transport of other cations through the truncated derivative channels, suggesting that cations are required for stabilizing the channel structure. In high concentrations of KCl, desfor and desval are nearly as effective as gramicidin in collapsing the mitochondrial membrane potential, and consequently, in the uncoupling of oxidative phosphorylation and enhancement of ATP hydrolysis. Preliminary experiments with liposomes show that 86Rb exchange is stimulated by desfor and desval almost to the same extend at gramicidin. These results strongly suggest that the truncated gramicidins form a novel conducting channel which differs from the gramicidin head-to-head, single-stranded β6.3-helical dimer (channel) in its conductance characteristic and its structure. On the basis of the secondary structure of the truncated derivatives, the authors suggest that the antiparallel double-stranded helix dimer (pore) is a likely alternative structure for this novel channel

  19. Liposomal dry powders as aerosols for pulmonary delivery of proteins

    OpenAIRE

    Lu, Dongmei; Hickey, Anthony J.

    2005-01-01

    The purpose of this research was to develop liposomal dry powder aerosols for protein delivery. The delivery of stable protein formulations is essential for protein subunit vaccine delivery, which requires local delivery to macrophages in the lungs. β-Glucuronidase (GUS) was used as a model protein to evaluate dry powder liposomes as inhaled delivery vehicles. Dimyristoyl phosphatylcholine:cholesterol (7∶3) was selected as the liposome composition. The lyophilization of liposomes, micronizati...

  20. Inhalable liposomal dry powder of gemcitabine-HCl: Formulation, in vitro characterization and in vivo studies.

    Science.gov (United States)

    Gandhi, Manit; Pandya, Tosha; Gandhi, Ravi; Patel, Sagar; Mashru, Rajashree; Misra, Ambikanandan; Tandel, Hemal

    2015-12-30

    Pulmonary drug delivery system facilitates local instillation of anticancer drugs to lungs which has proven to be pioneering approach for treatment of lung cancer. This approach led the groundwork for delivering liposomal formulation directly to lungs. Gemcitabine-HCl is currently considered as most effective drug for management of lung cancer. However, its application is limited owing to its metabolism by enzymes present in plasma resulting in reduced efficacy and higher toxicity. In present study, lyophilisation technique was used to convert liposomes into dry powder inhaler, which was formulated using emulsification solvent evaporation technique. The physicochemical properties including size, morphology, entrapment efficiency, loading efficiency etc. of formulated liposomes were evaluated. The prepared liposomal DPI (LDPI) formulations were then examined for solid state characteristics and aerosol performance using cascade impactor. From all the formulations prepared, the LDPI formulated using trehalose as cryoprotectant presented required properties along with desirable deposition pattern. Finally, the optimized formulation was selected for in vitro cell line studies; in vivo studies and stability study. This formulated inhalable particles offers a promising approach for the management of lung cancer through regional chemotherapy. PMID:26453787

  1. Liposomes Size Engineering by Combination of Ethanol Injection and Supercritical Processing.

    Science.gov (United States)

    Santo, Islane Espirito; Campardelli, Roberta; Albuquerque, Elaine Cabral; Vieira De Melo, Silvio A B; Reverchon, Ernesto; Della Porta, Giovanna

    2015-11-01

    Supercritical fluid extraction using a high-pressure packed tower is proposed not only to remove the ethanol residue from liposome suspensions but also to affect their size and distribution leading the production of nanosomes. Different operating pressures, temperatures, and gas to liquid ratios were explored and ethanol was successfully extracted up to a value of 400 ppm; liposome size and distribution were also reduced by the supercritical processing preserving their integrity, as confirmed by Z-potential data and Trasmission Electron Microscopy observations. Operating at 120 bar and 38°C, nanosomes with a mean diameter of about 180 ± 40 nm and good storage stability were obtained. The supercritical processing did not interfere on drug encapsulation, and no loss of entrapped drug was observed when the water-soluble fluorescein was loaded as a model compound. Fluorescein encapsulation efficiency was 30% if pure water was used during the supercritical extraction as processing fluid; whereas an encapsulation efficiency of 90% was obtained if the liposome suspension was processed in water/fluorescein solution. The described technology is easy to scale up to an industrial production and merge in one step the solvent extraction, liposome size engineering, and an excellent drug encapsulation in a single operation unit. PMID:26211426

  2. N-isopropylacrylamide copolymers for the preparation of pH-sensitive liposomes and polymeric micelles.

    Science.gov (United States)

    Leroux, J; Roux, E; Le Garrec, D; Hong, K; Drummond, D C

    2001-05-14

    Hydrophobically-modified copolymers of N-isopropylacrylamide bearing a pH-sensitive moiety were investigated for the preparation of pH-responsive liposomes and polymeric micelles. The copolymers having the hydrophobic anchor randomly distributed within the polymeric chain were found to more efficiently destabilize egg phosphatidylcholine (EPC)/cholesterol liposomes than the alkyl terminated polymers. Release of both a highly-water soluble fluorescent contents marker, pyranine, and an amphipathic cytotoxic anti-cancer drug, doxorubicin, from copolymer-modified liposomes was shown to be dependent on pH, the concentration of copolymer, the presence of other polymers such as polyethylene glycol, and the method of preparation. Both polymers were able to partially stabilize EPC liposomes in human serum. These polymers were found to self-assemble to form micelles. The critical association concentration was low (9--34 mg/l) and influenced by the position of the alkyl chains. In phosphate buffered saline, the micelles had a bimodal size distribution with the predominant population having a mean diameter of 35 nm. The polymeric micelles were studied as a delivery system for the photosensitizer aluminum chloride phthalocyanine, (AlClPc), currently evaluated in photodynamic therapy. pH-Responsive polymeric micelles loaded with AlClPc were found to exhibit increased cytotoxicity against EMT-6 mouse mammary cells in vitro than the control Cremophor EL formulation. PMID:11389986

  3. MRI shows clodronate-liposomes attenuating liverinjuryinratswithsevereacutepancreatitis

    Institute of Scientific and Technical Information of China (English)

    Jian-Xin Zhang; Sheng-Chun Dang; Yong Zhang; Xin Sha; Li-Rong Zhang; Chuan-She Wei; Min Chen; De-Li Jiang

    2010-01-01

    BACKGROUND: Studies have revealed that macrophages play an important role in the development of severe acute pancreatitis (SAP). Activated macrophages can lead to a systemic inlfammatory response, induce lipid peroxidation, impair membrane structure, result in injury to the liver and the other extrahepatic organs, and eventually result in multiple organ dysfunction syndrome by promoting excessive secretion of cytokines. Liver injury can further aggravate the systemic inlfammatory response and increase mortality by affecting the metabolism of toxins and the release of excessive inlfammatory mediators. Clodronate is a synthetic bisphosphonate, which is often used for treating bone changes caused by osteoporosis and other factors. In the current study, we created liposomes containing superparamagnetic iron oxide particles (SPIOs) for macrophage labeling and magnetic resonance imaging, using a novel method that can bind the clodronate to induce apoptosis and deplete macrophages. METHODS: Superparamagnetic Fe3O4 nanoparticles were prepared by chemical coprecipitation. SPIO-containing liposomes and SPIO-clodronate-containing liposomes were prepared by the thin iflm method. SAP models were prepared by injection of sodium taurocholate (2 ml/kg body weight) into the subcapsular space of the pancreas. Sprague-Dawley rats were randomly divided into a control group, a SAP plus SPIO-liposome group, and a SAP plus SPIO-clodronate-containing group. Two and six hours after SAP models were available, T2-weighted MRI scans (in the same plane) of the livers of rats in each group were performed. At the end of the scans, 2 ml of blood was taken from the superior mesenteric vein to measure the levels of serum amylase, ALT, AST, TNF-α, and IL-6. Pathological changes in the liver and pancreas were assessed. RESULTS: Transmission electron microscopy showed that the liposomes had a uniform size. No pathological changes in the pancreata of rats in the control group were noted. The

  4. Physico-chemical characterization of liposomes and drug substance-liposome interactions in pharmaceutics using capillary electrophoresis and electrokinetic chromatography

    DEFF Research Database (Denmark)

    Franzen, Ulrik; Østergaard, Jesper

    2012-01-01

    electrophoresis and liposome electrokinetic chromatography for the characterization of liposomes in a pharmaceutical context. Capillary electrophoretic techniques have been used for the measurement of electrophoretic mobility, which provides information on liposome surface charge, size and membrane permeability...... of liposomes. The use of liposome electrokinetic chromatography and capillary electrophoresis for determination of liposome/water partitioning and characterization of drug-liposome interactions is reviewed. A number of studies indicate that capillary electrophoresis may have a role in the...... characterization of liposome drug delivery systems, e.g., for the investigation of encapsulation efficiency and drug leakage. The well-known characteristics of capillary electrophoresis, i.e., low sample volume requirement, high separation efficiency in aqueous media without a stationary phase, minimal sample...

  5. Liposomes for scintigraphic imaging: optimization of in vivo behavior

    Energy Technology Data Exchange (ETDEWEB)

    Boerman, O.C.; Oyen, W.J.G.; Corstens, F.H.M. [Univ. Hospital Nijmegen (Netherlands). Dept. of Nuclear Medicine; Storm, G. [Utrecht Univ. (Netherlands). Utrecht Inst. for Pharmaceutics

    1998-12-01

    Liposomes, microscopic lipid vesicles consisting of concentric phospholipid bilayers enclosing discrete aqueous spaces, have been investigated extensively as carriers for drugs in attempts to achieve selective deposition and/or reduced toxicity. Liposomes radiolabeled with gamma emitters ({sup 67}Ga, {sup 111}In and {sup 99m}Tc) have been used for imaging purposes. Liposomes as formulated in the past, are rapidly taken up by cells of the mononuclear phagocyte system, primarily those located in liver and spleen. However, it has been shown during the last two decades that in vivo behavior of liposomes can be modulated by modifying their formulation. The size and the lipid composition have a major influence on the blood clearance rate, hepatic uptake and splenic uptake of liposomes. The development of long circulating liposomes, in particular coating of the bilayer with polyethyleneglycol (PEG) resulted in liposomes that oppose recognition by the MPS, thus displaying even longer circulatory half-lives. By carefully adjusting the liposomal formulation, the in vivo characteristics of liposomes can be tailored such that they become suitable vehicles for imaging various pathological processes in vivo. Liposomes have been proposed for tumor imaging, for infection imaging and as blood pool markers. Here, the factors that determine the in vivo behavior of liposomes and the current status of liposome-based radiopharmaceuticals are reviewed.

  6. Liposomes for scintigraphic imaging: optimization of in vivo behavior.

    Science.gov (United States)

    Boerman, O C; Oyen, W J; Corstens, F H; Storm, G

    1998-12-01

    Liposomes, microscopic lipid vesicles consisting of concentric phospholipid bilayers enclosing discrete aqueous spaces, have been investigated extensively as carries for drugs in attempts to achieve selective deposition and/or reduced toxicity. Liposomes radiolabeled with gamma emitters (67Ga, 111In and 99mTc) have been used for imaging purposes. Liposomes as formulated in the past, are rapidly taken up by cells of the mononuclear phagocyte system, primarily those located in liver and spleen. However, it has been shown during the last two decades that the in vivo behavior of liposomes can be modulated by modifying their formulation. The size and the lipid composition have a major influence on the blood clearance rate, hepatic uptake and splenic uptake of liposomes. The development of long circulating liposomes, in particular coating of the bilayer with polyethyleneglycol (PEG) resulted in liposomes that oppose recognition by the MPS, thus displaying even longer circulatory half-lives. By carefully adjusting the liposomal formulation, the in vivo characteristics of liposomes can be tailored such that they become suitable vehicles for imaging various pathological processes in vivo. Liposomes have been proposed for tumor imaging, for infection imaging and as blood pool markers. Here, the factors that determine the in vivo behavior of liposomes and the current status of liposome-based radiopharmaceuticals are reviewed. PMID:9973842

  7. 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

  8. Miniaturized bioanalytical systems: enhanced performance through liposomes.

    Science.gov (United States)

    Edwards, Katie A; Bolduc, Olivier R; Baeumner, Antje J

    2012-08-01

    Biorecognition-element labeled liposomes are simple and versatile tools used to amplify signals for the detection of analytes of environmental, clinical, food safety, and national security interest. Relying on measurement of encapsulated species via electrochemical or spectroscopic techniques, or properties inherent to liposomes themselves (such as mass, refractive index, or charge), many advances have been made in both bench-scale and microfluidic applications. Some of these measurement techniques are inherently sensitivity limited, but through the inclusion of liposomes, reduced limits of detection potentially broaden the utility towards otherwise challenging levels of analytes. Other advances took advantage of the hydrophobic environment required by many biorecognition elements to expand the target selectivity range or utilized the amphipathic nature of the lipid bilayer to provide enhanced separation capabilities. Novel handling approaches included wavelength-specific release of contents encapsulated within thermosensitive liposomes or application of electric fields to move, concentrate, and strategically lyse liposomes. These and other topics are discussed in terms of either present incorporation or adaptation to microfluidic devices. PMID:22673065

  9. Cationic Polyene Phospholipids as DNA Carriers for Ocular Gene Therapy

    Directory of Open Access Journals (Sweden)

    Susana Machado

    2014-01-01

    Full Text Available Recent success in the treatment of congenital blindness demonstrates the potential of ocular gene therapy as a therapeutic approach. The eye is a good target due to its small size, minimal diffusion of therapeutic agent to the systemic circulation, and low immune and inflammatory responses. Currently, most approaches are based on viral vectors, but efforts continue towards the synthesis and evaluation of new nonviral carriers to improve nucleic acid delivery. Our objective is to evaluate the efficiency of novel cationic retinoic and carotenoic glycol phospholipids, designated C20-18, C20-20, and C30-20, to deliver DNA to human retinal pigmented epithelium (RPE cells. Liposomes were produced by solvent evaporation of ethanolic mixtures of the polyene compounds and coformulated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE or cholesterol (Chol. Addition of DNA to the liposomes formed lipoplexes, which were characterized for binding, size, biocompatibility, and transgene efficiency. Lipoplex formulations of suitable size and biocompatibility were assayed for DNA delivery, both qualitatively and quantitatively, using RPE cells and a GFP-encoding plasmid. The retinoic lipoplex formulation with DOPE revealed a transfection efficiency comparable to the known lipid references 3β-[N-(N′,N′-dimethylaminoethane-carbamoyl]-cholesterol (DC-Chol and 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (EPC and GeneJuice. The results demonstrate that cationic polyene phospholipids have potential as DNA carriers for ocular gene therapy.

  10. Nanomedicine for glaucoma: liposomes provide sustained release of latanoprost in the eye

    Directory of Open Access Journals (Sweden)

    Natarajan JV

    2012-01-01

    Full Text Available Jayaganesh V Natarajan1*, Marcus Ang2*, Anastasia Darwitan1, Sujay Chattopadhyay3, Tina T Wong2, Subbu S Venkatraman1 1Materials Science and Engineering, Nanyang Technological University, Singapore; 2Singapore Eye Research Institute, Singapore; 3Polymer Division, Indian Institute of Technology Roorkee, India*These authors contributed equally to this workPurpose: To report the development and therapeutic evaluation of a liposomal nanocarrier for sustained release of latanoprost, in the rabbit eye.Methods: We fabricated latanoprost-loaded egg-phosphatidylcholine (EggPC liposomes using the film hydration technique. The delivery vehicles were nano-sized (Z avg = 109 ± 18 nm, had a narrow poly dispersity index (PDI = 0.19 ± 0.04, and a very high loading efficiency (94% ± 5%. Based on in vitro data, we evaluated this formulation for lowering intraocular pressure (IOP in rabbit eyes. Following a single subconjunctival injection of the latanoprost loaded formulation, the eyes were clinically monitored and the IOP recorded.Results: Latanoprost-loaded EggPC liposomes demonstrated a high drug/lipid mole ratio of 0.181, remained stable for at least 6 months on storage (4°C, and at least 1 month at 25°C. A slow and sustained release of 60% of latanoprost was achieved by 14 days in the in vitro release study. The same formulation demonstrated a greater sustained IOP lowering effect compared with daily administration of topical latanoprost beyond 90 days (4.8 ± 1.5 vs 2.5 ± 0.9 mmHg; P < 0.001. No signs of inflammation were evident in the eyes from slit-lamp examination analysis.Conclusion: The loading required for a long-term sustained delivery of latanoprost for up to 90 days in the rabbit eyes was achieved with EggPC liposomes. A single injection of latanoprost-loaded EggPC liposomes can lower the IOP for up to 90 days, with a greater IOP lowering effect than daily topical administration of latanoprost.Keywords: nanomedicine, nanoliposomes, Egg

  11. Preparation of redispersible liposomal dry powder using an ultrasonic spray freeze-drying technique for transdermal delivery of human epithelial growth factor

    Directory of Open Access Journals (Sweden)

    Yin F

    2014-03-01

    Full Text Available Fei Yin,1 Shiyan Guo,2 Yong Gan,2 Xinxin Zhang21Department of Pharmacy, Liaoning Cancer Hospital and Institute, Shenyang, 2Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai, People's Republic of ChinaAbstract: In this work, an ultrasonic spray freeze-drying (USFD technique was used to prepare a stable liposomal dry powder for transdermal delivery of recombinant human epithelial growth factor (rhEGF. Morphology, particle size, entrapment efficiency, in vitro release, and skin permeability were systematically compared between rhEGF liposomal dry powder prepared using USFD and that prepared using a conventional lyophilization process. Porous and spherical particles with high specific area were produced under USFD conditions. USFD effectively avoided formation of ice crystals, disruption of the bilayer structure, and drug leakage during the liposome drying process, and maintained the stability of the rhEGF liposomal formulation during storage. The reconstituted rhEGF liposomes prepared from USFD powder did not show significant changes in morphology, particle size, entrapment efficiency, or in vitro release characteristics compared with those of rhEGF liposomes before drying. Moreover, the rhEGF liposomal powder prepared with USFD exhibited excellent enhanced penetration in ex vivo mouse skin compared with that for powder prepared via conventional lyophilization. The results suggest that ultrasonic USFD is a promising technique for the production of stable protein-loaded liposomal dry powder for application to the skin.Keywords: spray freeze-drying, recombinant human epithelial growth factor, liposomes, skin permeability, transdermal drug delivery

  12. Cation-cation interaction in neptunyl(V) compounds

    International Nuclear Information System (INIS)

    The original manuscript was prepared by Professor N.N. Krot of Institute of Physical Chemistry, Russian Academy of Sciences, in 1997. Saeki tried to translate that into Japanese and to add some new data since 1997. The contents include the whole picture of cation-cation interactions mainly in 5-valence neptunium compounds. Firstly, characteristic structures of neptunium are summarized of the cation-cation bonding in compounds. Secondly, it is mentioned how the cation-cation bonding affects physical and chemical properties of the compounds. Then, characterization-methods for the cation-cation bonding in the compounds are discussed. Finally, the cation-cation interactions in compounds of other actinide-ions are shortly reviewed. (author)

  13. Dehydration resistance of liposomes containing trehalose glycolipids

    Science.gov (United States)

    Nyberg, Kendra; Goulding, Morgan; Parthasarathy, Raghuveer

    2010-03-01

    The pathogen, Mycobacterium tuberculosis, has an unusual outer membrane containing trehalose glycolipids that may contribute to its ability to survive freezing and dehydration. Based on our recent discovery that trehalose glycolipids confer dehydration resistance to supported lipid monolayers (Biophys. J. 94: 4718-4724 (2008); Langmuir 25: 5193-5198, (2009)), we hypothesized that liposomes containing synthetic trehalose glycolipids may be dehydration-resistant as well. To test this, we measured the leakage of encapsulated fluorophores and larger macromolecular cargo from such liposomes subject to freeze drying. Both leakage assays and size measurements show that the liposomes are dehydration-resistant. In addition to demonstrating a possibly technologically useful encapsulation platform, our results corroborate the view that encapsulation in a trehalose-glycolipid-rich membrane is a biophysically viable route to protection of mycobacteria from environmental stresses.

  14. Enhanced oral bioavailability of silymarin using liposomes containing a bile salt: preparation by supercritical fluid technology and evaluation in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Yang G

    2015-10-01

    Full Text Available Gang Yang,1 Yaping Zhao,2 Yongtai Zhang,1 Beilei Dang,1 Ying Liu,1 Nianping Feng11School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 2School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaAbstract: The aim of this investigation was to develop a procedure to improve the dissolution and bioavailability of silymarin (SM by using bile salt-containing liposomes that were prepared by supercritical fluid technology (ie, solution-enhanced dispersion by supercritical fluids [SEDS]. The process for the preparation of SM-loaded liposomes containing a bile salt (SM-Lip-SEDS was optimized using a central composite design of response surface methodology with the ratio of SM to phospholipids (w/w, flow rate of solution (mL/min, and pressure (MPa as independent variables. Particle size, entrapment efficiency (EE, and drug loading (DL were dependent variables for optimization of the process and formulation variables. The particle size, zeta potential, EE, and DL of the optimized SM-Lip-SEDS were 160.5 nm, -62.3 mV, 91.4%, and 4.73%, respectively. Two other methods to produce SM liposomes were compared to the SEDS method. The liposomes obtained by the SEDS method exhibited the highest EE and DL, smallest particle size, and best stability compared to liposomes produced by the thin-film dispersion and reversed-phase evaporation methods. Compared to the SM powder, SM-Lip-SEDS showed increased in vitro drug release. The in vivo AUC0-t of SM-Lip-SEDS was 4.8-fold higher than that of the SM powder. These results illustrate that liposomes containing a bile salt can be used to enhance the oral bioavailability of SM and that supercritical fluid technology is suitable for the preparation of liposomes.Keywords: silymarin, solution-enhanced dispersion by supercritical fluids, liposomes, bile salt, bioavailability

  15. Microfluidic-enabled liposomes elucidate size-dependent transdermal transport.

    Directory of Open Access Journals (Sweden)

    Renee R Hood

    Full Text Available Microfluidic synthesis of small and nearly-monodisperse liposomes is used to investigate the size-dependent passive transdermal transport of nanoscale lipid vesicles. While large liposomes with diameters above 105 nm are found to be excluded from deeper skin layers past the stratum corneum, the primary barrier to nanoparticle transport, liposomes with mean diameters between 31-41 nm exhibit significantly enhanced penetration. Furthermore, multicolor fluorescence imaging reveals that the smaller liposomes pass rapidly through the stratum corneum without vesicle rupture. These findings reveal that nanoscale liposomes with well-controlled size and minimal size variance are excellent vehicles for transdermal delivery of functional nanoparticle drugs.

  16. 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.

  17. Preparation of vinorelbine bitartrate long-circulating liposomes by ionophore A23187-mediated pH gradient method%离子载体A23187介导pH梯度法制备重酒石酸长春瑞滨长循环脂质体

    Institute of Scientific and Technical Information of China (English)

    杨光丽; 张冰; 赵利刚; 张勇; 王栋海; 尹青; 杨清敏

    2012-01-01

    目的:采用A23187制备重酒石酸长春瑞滨长循环脂质体,优化了处方工艺,并考察了含量、包封率、药脂比和体外释放等检测指标.方法:采用A23187介导的pH梯度法制备了重酒石酸长春瑞滨脂质体;用HPLC法检测了脂质体中重酒石酸长春瑞滨的含量和脂质(HSPC)的含量,考察了药脂比;采用阳离子交换树脂分离脂质体和游离药物,HPLC法检测包封率;以4 mmol· L- NH4Cl-PBS(pH 7.4)为体外释放介质考察了脂质体的体外释放行为.结果:重酒石酸长春瑞滨脂质体包封率为96.1%,药脂比为1:5(w/w);高药脂比有利于延长药物体外释放的时间.结论:采用A23187介导的pH梯度法制备重酒石酸长春瑞滨脂质体工艺可行、载药量大、包封率高;所建立体外释放的检测方法快速、准确.%Objective: To prepare vinorelbine bitartrate long-circulating liposomes and optimize the formulation and process parameters, and to investigate vinorelbine contents, entrapment efficiency, drug-to-lipid ratio, in vitro release rate of the liposomal vinorelbine. Methods: Vinorelbine bitartrate liposomes were prepared in response to a transmembrane pH gradient that was generated by the use of ionophore A23187. Drug-to-lipid ratio was calculated by vinorelbine bitartrate content and HSPC content that were determined by HPLC. Free vinorelbine and liposomal vinorelbine were separated by cation exchange resin ultraviolet, and the encapsulation efficiency was determined by HPLC. The in vitro release behavior was investigated in 4 mmol·L-1 NH4C1-PBS ( pH 7.4). Results: The encapsulation efficiency and drug-to-lipid ratio of the vinorelbine liposomes were 96. 1% and 1:5 (mass ratio) , respectively. The higher drug-to-lipid ratio reduced the in vitro release rate of vinorelbine from liposomes. Conclusion: The ionophore A23187-loading technique is feasible for preparing vinorelbine bitartrate long-circulating liposomes. The drug loading and

  18. Development of a novel lipidic nanoparticle probe using liposomal encapsulated Gd₂O₃-DEG for molecular MRI.

    Science.gov (United States)

    Zohdiaghdam, R; Riyahi-Alam, N; Moghimi, H R; Haghgoo, S; Alinaghi, A; Azizian, Gh; Ghanaati, H; Gorji, E; Rafiei, B

    2013-01-01

    Recently, it has been showed that gadolinium oxide nanoparticles can provide high-contrast enhancement in magnetic resonance imaging (MRI). Moreover, liposomes due to high biocompatibility have shown unique model systems, with the most successful application being the drug delivery system. As a suitable cell-tracking contrast agent (CA) in molecular MRI (mMRI), the synthesis and optimisation characteristic of a novel paramagnetic liposomes (PMLs) based on gadolinium nanoparticles, essentially composed of a new complex of gadolinium oxide-diethylene glycol (Gd₂O₃-DEG) loaded in liposomes have been determined in this research. Gd₂O₃-DEG was prepared by a new supervised polyol method and was encapsulated with liposome by the film hydration method. The paramagnetic liposome nanoparticle (PMLN) sizes ranged from 65 to 170 nm. The r₁ of PMLNs and Gd₂O₃-DEG were much higher than that of Gd-diethylenetriamine penta-acetic acid (Gd-DTPA). In MC/9 cell lines, the experiments showed similar results as in water. PMLNs with lower T₁ than Gd-DTPA are sensitive, positive MRI CA that could be attractive candidates for cellular and molecular lipid content targets such as diagnostic applications. PMID:23915304

  19. Simultaneous determination of active component and vehicle penetration from F-DPPC liposomes into porcine skin layers.

    Science.gov (United States)

    Mahrhauser, Denise-Silvia; Reznicek, Gottfried; Gehrig, Sebastian; Geyer, Antonia; Ogris, Manfred; Kieweler, Ruth; Valenta, Claudia

    2015-11-01

    Liposomes have been used as innovative delivery vehicles on skin for a number of years due to their positive influence on skin penetration. However, until now it is not entirely clear how and by which mechanism enhancement is achieved. In the present study, the skin permeation of a model substance incorporated into liposomes and a control formulation was compared to study the influence of the vehicle in Franz-type diffusion cell experiments. Furthermore, the penetration depths of both components were studied by simultaneous determination of the active substance and the vehicle component during tape stripping studies and horizontal sectioning. For these purposes we prepared liposomes with 1-palmitoyl-2-(16-fluoropalmitoyl)-sn-glycero-3-phosphocholine (F-DPPC), the monofluorinated analogue of dipalmitoylphosphaditylcholine (DPPC) loaded with sodium fluorescein (SoFl). A sodium-fluorescein solution was used as control formulation. While the semi-solid F-DPPC liposomes and the SoFl-solution performed equally well with similar permeation profiles during skin diffusion experiments, superior penetrated amounts of SoFl into the stratum corneum (SC) from F-DPPC liposomes compared to the SoFl-solution were observed possibly due to a "push" exerted by the vehicle F-DPPC. We also showed that SoFl penetrated through SC into the viable epidermis. PMID:26493713

  20. Metalloporphyrin intercalation in liposome membranes: ESR study

    OpenAIRE

    Man, Dariusz; Słota, Rudolf; Małgorzata A. Broda; Mele, Giuseppe; Li, Jun

    2010-01-01

    Liposomes characterized by membranes featuring diverse fluidity (liquid-crystalline and/or gel phase), prepared from egg yolk lecithin (EYL) and dipalmitoylphosphatidylcholine (DPPC), were doped with selected metalloporphyrins and the time-related structural and dynamic changes within the lipid double layer were investigated. Porphyrin complexes of Mg(II), Mn(III), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), and the metal-free base were embedded into the particular liposome systems and tested fo...

  1. Application of Liposomes for Construction of Vaccines

    Czech Academy of Sciences Publication Activity Database

    Turánek, J.; Mašek, J.; Raška, M.; Ledvina, Miroslav

    Rijeka: InTech, 2012 - (Ghista, D.), s. 653-678 ISBN 978-953-307-471-9 R&D Projects: GA ČR(CZ) GAP304/10/1951; GA AV ČR(CZ) KAN200520703; GA AV ČR KAN200100801 Institutional research plan: CEZ:AV0Z40550506 Keywords : liposomes * metallochelation * recombinant vaccines * adjuvants Subject RIV: CC - Organic Chemistry http://www.intechopen.com/books/biomedical-science-engineering-and-technology/application-of-liposomes-for-construction-of-vaccines

  2. High-efficiency liposomal encapsulation of a tyrosine kinase inhibitor leads to improved in vivo toxicity and tumor response profile

    Directory of Open Access Journals (Sweden)

    Mukthavaram R

    2013-10-01

    Full Text Available Rajesh Mukthavaram,1 Pengfei Jiang,1 Rohit Saklecha,1 Dmitri Simberg,3,4 Ila Sri Bharati,1 Natsuko Nomura,1 Ying Chao,1 Sandra Pastorino,1 Sandeep C Pingle,1 Valentina Fogal,1 Wolf Wrasidlo,1,2 Milan Makale,1,2 Santosh Kesari1,21Translational Neuro-Oncology Laboratories, 2Department of Neurosciences, 3Solid Tumor Therapeutics Program, Moores Cancer Center, UC San Diego, La Jolla, CA, 4Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Denver, CO, USAAbstract: Staurosporine (STS is a potent pan-kinase inhibitor with marked activity against several chemotherapy-resistant tumor types in vitro. The translational progress of this compound has been hindered by poor pharmacokinetics and toxicity. We sought to determine whether liposomal encapsulation of STS would enhance antitumor efficacy and reduce toxicity, thereby supporting the feasibility of further preclinical development. We developed a novel reverse pH gradient liposomal loading method for STS, with an optimal buffer type and drug-to-lipid ratio. Our approach produced 70% loading efficiency with good retention, and we provide, for the first time, an assessment of the in vivo antitumor activity of STS. A low intravenous dose (0.8 mg/kg inhibited U87 tumors in a murine flank model. Biodistribution showed preferential tumor accumulation, and body weight data, a sensitive index of STS toxicity, was unaffected by liposomal STS, but did decline with the free compound. In vitro experiments revealed that liposomal STS blocked Akt phosphorylation, induced poly(ADP-ribose polymerase cleavage, and produced cell death via apoptosis. This study provides a basis to explore further the feasibility of liposomally encapsulated STS, and potentially related compounds for the management of resistant solid tumors.Keywords: liposomes, staurosporine, glioblastoma, biodistribution, efficacy

  3. The development of poly-L-arginine-coated liposomes for gene delivery

    Directory of Open Access Journals (Sweden)

    Opanasopit P

    2011-10-01

    Full Text Available Praneet Opanasopit1, Jintana Tragulpakseerojn1, Auayporn Apirakaramwong1, Tanasait Ngawhirunpat1, Theerasak Rojanarata1, Uracha Ruktanonchai21Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand; 2National Nanotechnology Center, Thailand Science Park, Pathumthani, Thailand Abstract: In this study, liposomes coated with cationic polymers, poly-L-arginine (PLA, were assessed as a promising gene transfer system in human cervical carcinoma (HeLa cells and human hepatoma cell line (Huh7 cells. The liposomes were prepared using egg yolk phosphatidylcholine and sodium oleate in the molar ratio of 10:2 with an ultrasonic generator and then coated with PLA. The PLA-coated liposomes (PCLs formed complexes with plasmid DNA encoding green fluorescent protein. The complexes were characterized by agarose gel electrophoresis and investigated for their transfection efficiency in HeLa and Huh7 cells. The data were compared with PLA/DNA complexes and the positive control Lipofectamine 2000TM. The results showed that complete PCL/DNA complexes were formed at weight ratios of more than 0.05. Efficient gene transfer by PCLs was dependent on the cell type. The transfection efficiency of PCLs was about two times higher than that of PLA/DNA complexes in both HeLa cells and Huh7 cells. Cytotoxicity was determined by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide assay and showed that 80%-100% of both of the cells were viable after treating PCL/DNA complexes. The present results demonstrate that PCLs are a promising, nonviral gene carrier with low toxicity.Keywords: PLA-coated liposomes, PLA, gene delivery, transfection efficiency 

  4. 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.

  5. CLINICAL PHARMACOKINETIC ASPECTS OF STEALTH LIPOSOMES: A REVIEW

    Directory of Open Access Journals (Sweden)

    Drabu Sushma, Khanna Surabhi

    2010-12-01

    Full Text Available Stealth liposomes are long-circulating liposomes with inclusion of the synthetic polymer poly-(ethylene glycol (PEG in liposome composition. The presence of PEG on the surface of the liposomal carrier has been shown to extend bloodcirculation time while reducing mononuclear phagocyte system uptake. Further these liposomes exhibit increasing drug stability and solubility, lowering toxicity, increasing half-life, decreasing clearance and immunogenicity. Sterically stabilized vesicles can act either as long circulating micro reservoirs or tumour (or site of inflammation and infection targeting vehicles. The former applications require larger liposomes (0.2µm while the latter one is due to the ability of small vesicles to leave the blood circulation. The altered biodistribution of stealth liposomes, in addition to the accumulation at the sites characterised with porous blood capillaries, such as in tumors, inflammations, and infections. A pharmacogenomic approach for delivery of siRNA to cells is the use of liposomes as targeted delivery vehicles. Stealth technology summarizes pre-clinical and clinical data relating to the principal liposome formulations, encapsulating active molecules, with high target efficiency and activity. Further these liposomes offer improvements in bioreclamation and various monitoring and analytical-diagnostic applications. The paper reviews the clinical aspects of these liposomes with longer therapeutic half lives in diseases like Reconstitution of membrane proteins into artificial membranes, model biological membranes, cell function, fusion, recognition , pharmaceutics studies of drug action , medicine drug-delivery and medical diagnostics, gene therapy and there extensive use in the pharmaceutical industry.

  6. Co-liposomes having anisamide tagged lipid and cholesteryl tryptophan trigger enhanced gene transfection in sigma receptor positive cells.

    Science.gov (United States)

    Misra, Santosh K; Moitra, Parikshit; Kondaiah, Paturu; Bhattacharya, Santanu

    2016-06-01

    Selective gene transfection could be strategy of interest for reducing off-target gene expression and toxicity. In this respect, sigma receptors are found to be over-expressed in many human tumors and liposomal formulations with ability to target these sigma receptors may improve the transfection efficiency to a significant level. To this direction, six novel lipids have been synthesized with different hydrophobic segments such as a long hydrophobic chain or a cholesteryl group and L-tryptophan as the head group. Three of them, Lipid 1, 3 and 5 possessed cationic Me3N(+) moiety at the distal end. In contrast each of the other three Lipid 2, 4 and 6 possessed sigma receptor targeting anisamide group with no cationic charge. Mixing of cationic and anisamide counterparts of the same lipid in a molar ratio of 1:1 produced co-liposomes L-M-1 (Lipid 1+2), L-M-2 (Lipid 3+4) and L-M-3 (Lipid 5+6). These co-liposomes, while keeping the sigma targeting anisamide tag intact, showed good DNA binding and release which were optimized from EB intercalation and gel electrophoresis assays. Inclusion of a zwitterionic, fusogenic natural lipid, DOPE, into the co-liposomes further improved the binding efficiencies of the lipid mixtures with DNA. These co-liposomes having cationic and anisamide lipids and DOPE were highly selective toward sigma positive HEK293 and HEK293T cells compared to the sigma negative HeLa cells. As evidenced from both FACS and luciferase assay, a lipid mixture comprising Lipid 3, 4 and DOPE in a molar ratio of 1:1:1 (L-M-2D1) was the best for transfection of reporter pEGFP-C3 and functional pCEP4-p53 gene plasmids. Anisamide mediated sigma receptor selectivity was further probed by pre-incubating the transfecting cells with lipids possessing anisamide and by quantification of the un-transfected plasmid DNA. Also each formulation was highly non-toxic in the cell lines examined. PMID:26945165

  7. Development of a cell-based bioassay for phospholipase A2-triggered liposomal drug release.

    Directory of Open Access Journals (Sweden)

    Ahmad Arouri

    Full Text Available The feasibility of exploiting secretory phospholipase A2 (sPLA2 enzymes, which are overexpressed in tumors, to activate drug release from liposomes precisely at the tumor site has been demonstrated before. Although the efficacy of the developed formulations was evaluated using in vitro and in vivo models, the pattern of sPLA2-assisted drug release is unknown due to the lack of a suitable bio-relevant model. We report here on the development of a novel bioluminescence living-cell-based luciferase assay for the monitoring of sPLA2-triggered release of luciferin from liposomes. To this end, we engineered breast cancer cells to produce both luciferase and sPLA2 enzymes, where the latter is secreted to the extracellular medium. We report on setting up a robust and reproducible bioassay for testing sPLA2-sensitive, luciferin remote-loaded liposomal formulations, using 1,2-distearoyl-sn-glycero-3-phosphatidylcholine/1,2-distearoyl-sn-glycero-3-phosphatidylglycerol (DSPC/DSPG 7:3 and DSPC/DSPG/cholesterol 4:3:3 as initial test systems. Upon their addition to the cells, the liposomes were degraded almost instantaneously by sPLA2 releasing the encapsulated luciferin, which provided readout from the luciferase-expressing cells. Cholesterol enhanced the integrity of the formulation without affecting its susceptibility to sPLA2. PEGylation of the liposomes only moderately broadened the release profile of luciferin. The provided bioassay represents a useful tool for monitoring active drug release in situ in real time as well as for testing and optimizing of sPLA2-sensitive lipid formulations. In addition, the bioassay will pave the way for future in-depth in vitro and in vivo studies.

  8. 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.

  9. Study on Leakage of Sesame (Sesamum indicum L. and Coconut (Cocos nucifera L. Liposomes

    Directory of Open Access Journals (Sweden)

    Dwi Hudiyanti

    2015-03-01

    Full Text Available Leakage phenomena on sesame (Sesamum indicum L. and coconut (Cocos nucifera L. liposomes has been studied to evaluate their ability as drug delivery materials. Permeation of carboxyfluorescein through the liposomes with and without added cholesterol was examined. Sesame liposomes release carboxyfluorescein less than coconut liposomes in all circumstances. Sesame liposomes save about 50% of payload after 17 hours of storage while coconut liposomes only 10%. Addition of cholesterol has increase storage capability of all liposomes. The sesame-cholesterol and coconut-cholesterol liposomes save greater amount of payload compare to the original. Sesame liposomes have better potency as drug delivery systems.

  10. Properties of liposomal membranes containing lysolecithin.

    Science.gov (United States)

    Kitagawa, T; Inoue, K; Nojima, S

    1976-06-01

    Liposomes have been prepared with lysolecithin (1-acyl-sn-3-glycerylphosphorylcholine), egg lecithin (3-sn-phosphatidylcholine), dicetyl phosphate, and cholesterol. The ability to function as a barrier to the diffusion of glucose marker and the sensitivities of the liposomes to hypotonic treatment and other reagents which modified the permeability were examined. Generally, lysolecithin incorporation decreased the effectiveness of the membranes as a barrier to glucose and made the membranes more "osmotically fragile." Cholesterol incorporation counteracted the effect of incorporated lysolecithin. The more cholesterol incorporated into liposomes, the more lysolecthin could be incorporated into the membrane without loss of function as a barrier. With more than 50 mole% of colesterol, lysolecithin alone could form membranes which were practically impermeable to glucose. The hemolytic activity of lysolecithin was affected by mixing with various lecithins or cholesterol. Liposomes containing lysolecithin, which have the ability to trap glucose marker, showed poor hemolytic activity, while lipid micelles with lysolecithin (which could trap little glucose) showed almost the same hemolytic activity as lysolecithin itself. There seems to be a close correlation between hemolytic activity and barrier function of lipid micelles. PMID:986392

  11. Lipogels: surface-adherent composite hydrogels assembled from poly(vinyl alcohol) and liposomes

    Science.gov (United States)

    Jensen, Bettina E. B.; Hosta-Rigau, Leticia; Spycher, Philipp R.; Reimhult, Erik; Städler, Brigitte; Zelikin, Alexander N.

    2013-07-01

    Drug-eluting engineered surface coatings are of paramount importance for many biomedical applications from implantable devices to tissue engineering. Herein, we present the assembly of lipogels, composite physical hydrogels assembled from poly(vinyl alcohol) and liposomes using thiol-disulfide exchange between end group modified PVA and thiocholesterol containing liposomes, and the response of adhering cells to these coatings. We demonstrate the controlled loading of liposomes into the polymer matrix and the preserved mechanical properties of the lipogels. Furthermore, the lipogels are successfully rendered cell adhesive by incorporation of poly(l-lysine) into the PVA polymer matrix or by poly(dopamine) coating of the lipogels. The successful lipid uptake from the lipogels by macrophages, hepatocytes, and myoblasts was monitored by flow cytometry. Finally, the delivery of active cargo, paclitaxel, to adherent myoblasts is shown, thus illustrating the potential of the lipogels as a drug eluting interface for biomedical applications.Drug-eluting engineered surface coatings are of paramount importance for many biomedical applications from implantable devices to tissue engineering. Herein, we present the assembly of lipogels, composite physical hydrogels assembled from poly(vinyl alcohol) and liposomes using thiol-disulfide exchange between end group modified PVA and thiocholesterol containing liposomes, and the response of adhering cells to these coatings. We demonstrate the controlled loading of liposomes into the polymer matrix and the preserved mechanical properties of the lipogels. Furthermore, the lipogels are successfully rendered cell adhesive by incorporation of poly(l-lysine) into the PVA polymer matrix or by poly(dopamine) coating of the lipogels. The successful lipid uptake from the lipogels by macrophages, hepatocytes, and myoblasts was monitored by flow cytometry. Finally, the delivery of active cargo, paclitaxel, to adherent myoblasts is shown, thus

  12. GE11-modified liposomes for non-small cell lung cancer targeting: preparation, ex vitro and in vivo evaluation

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    Cheng L

    2014-02-01

    Full Text Available Liang Cheng,1,* Fa-Zhen Huang,1,2,* Li-Fang Cheng,1 Ya-Qin Zhu,1 Qing Hu,1 Ling Li,1 Lin Wei1, Da-Wei Chen1 1Department of Pharmaceutics, College of Pharmaceutical Science, Soochow University, Suzhou, Jiangsu Province, 2Department of Pharmacy, Central Hospital of Zaozhuang Minging Group, Zaozhuang, Shandong Province, People's Republic of China *These authors contributed equally to this work Abstract: Non-small cell lung cancer (NSCLC is a serious threat to human health, and 40%–80% of NSCLCs express high levels of epidermal growth factor receptor (EGFR. GE11 is a novel peptide and exhibits high affinity for EGFR binding. The aim of this study was to construct and evaluate GE11-modified liposomes for targeted drug delivery to EGFR-positive NSCLC. Doxorubicin, a broad-spectrum antitumor agent, was chosen as the payload. GE11 was conjugated to the distal end of DSPE-PEG2000-Mal by an addition reaction with a conjugation efficiency above 90%. Doxorubicin-loaded liposomes containing GE11 (GE11-LP/DOX at densities ranging from 0% to 15% were prepared by combination of a thin film hydration method and a post insertion method. Irrespective of GE11 density, the physicochemical properties of these targeted liposomes, including particle size, zeta potential, and drug entrapment efficiency, were nearly identical. Interestingly, the cytotoxic effect of the liposomes on A549 tumor cells was closely related to GE11 density, and liposomes with 10% GE11 had the highest tumor cell killing activity and a 2.6-fold lower half maximal inhibitory concentration than that of the nontargeted counterpart (PEG-LP/DOX. Fluorescence microscopy and flow cytometry analysis revealed that GE11 significantly increased cellular uptake of the liposomes, which could be ascribed to specific EGFR-mediated endocytosis. It was found that multiple endocytic pathways were involved in entry of GE11-LP/DOX into cells, but GE11 assisted in cellular internalization mainly via the clathrin

  13. Liposomal encapsulated rhodomyrtone: a novel antiacne drug.

    Science.gov (United States)

    Chorachoo, Julalak; Amnuaikit, Thanaporn; Voravuthikunchai, Supayang P

    2013-01-01

    Rhodomyrtone isolated from the leaves of Rhodomyrtus tomentosa possesses antibacterial, anti-inflammatory, and anti-oxidant activities. Since rhodomyrtone is insoluble in water, it is rather difficult to get to the target sites in human body. Liposome exhibited ability to entrap both hydrophilic and hydrophobic compounds and easily penetrate to the target site. The present study aimed to develop a novel liposomal encapsulated rhodomyrtone formulations. In addition, characterization of liposome, stability profiles, and their antiacne activity were performed. Three different formulations of total lipid concentrations 60, 80, and 100  μ mol/mL were used. Formulation with 60  μ mol/mL total lipid (phosphatidylcholine from soybean and cholesterol from lanolin in 4 : 1, w/w) exhibited the highest rhodomyrtone encapsulation efficacy (65.47 ± 1.7%), average particle size (209.56 ± 4.8 nm), and ζ -potential (-41.19 ± 1.3 mV). All formulations demonstrated good stability when stored for 2 months in dark at 4°C as well as room temperature. Minimal inhibitory concentration and minimal bactericidal concentration values of liposomal formulation against 11 clinical bacterial isolates and reference strains ranged from 1 to 4 and from 4 to 64  μ g/mL, respectively, while those of rhodomyrtone were 0.25-1 and 0.5-2  μ g/mL, respectively. The MIC and MBC values of liposome formulation were more effective than topical drugs against Staphylococcus aureus and Staphylococcus epidermidis. PMID:23762104

  14. Liposomal Encapsulated Rhodomyrtone: A Novel Antiacne Drug

    Directory of Open Access Journals (Sweden)

    Julalak Chorachoo

    2013-01-01

    Full Text Available Rhodomyrtone isolated from the leaves of Rhodomyrtus tomentosa possesses antibacterial, anti-inflammatory, and anti-oxidant activities. Since rhodomyrtone is insoluble in water, it is rather difficult to get to the target sites in human body. Liposome exhibited ability to entrap both hydrophilic and hydrophobic compounds and easily penetrate to the target site. The present study aimed to develop a novel liposomal encapsulated rhodomyrtone formulations. In addition, characterization of liposome, stability profiles, and their antiacne activity were performed. Three different formulations of total lipid concentrations 60, 80, and 100 μmol/mL were used. Formulation with 60 μmol/mL total lipid (phosphatidylcholine from soybean and cholesterol from lanolin in 4 : 1, w/w exhibited the highest rhodomyrtone encapsulation efficacy (65.47 ± 1.7%, average particle size (209.56 ± 4.8 nm, and ζ-potential (–41.19 ± 1.3 mV. All formulations demonstrated good stability when stored for 2 months in dark at 4°C as well as room temperature. Minimal inhibitory concentration and minimal bactericidal concentration values of liposomal formulation against 11 clinical bacterial isolates and reference strains ranged from 1 to 4 and from 4 to 64 μg/mL, respectively, while those of rhodomyrtone were 0.25–1 and 0.5–2 μg/mL, respectively. The MIC and MBC values of liposome formulation were more effective than topical drugs against Staphylococcus aureus and Staphylococcus epidermidis.

  15. Internalization of paramagnetic phosphatidylserine-containing liposomes by macrophages

    Directory of Open Access Journals (Sweden)

    Geelen Tessa

    2012-08-01

    Full Text Available Abstract Background Inflammation plays an important role in many pathologies, including cardiovascular diseases, neurological conditions and oncology, and is considered an important predictor for disease progression and outcome. In vivo imaging of inflammatory cells will improve diagnosis and provide a read-out for therapy efficacy. Paramagnetic phosphatidylserine (PS-containing liposomes were developed for magnetic resonance imaging (MRI and confocal microscopy imaging of macrophages. These nanoparticles also provide a platform to combine imaging with targeted drug delivery. Results Incorporation of PS into liposomes did not affect liposomal size and morphology up to 12 mol% of PS. Liposomes containing 6 mol% of PS showed the highest uptake by murine macrophages, while only minor uptake was observed in endothelial cells. Uptake of liposomes containing 6 mol% of PS was dependent on the presence of Ca2+ and Mg2+. Furthermore, these 6 mol% PS-containing liposomes were mainly internalized into macrophages, whereas liposomes without PS only bound to the macrophage cell membrane. Conclusions Paramagnetic liposomes containing 6 mol% of PS for MR imaging of macrophages have been developed. In vitro these liposomes showed specific internalization by macrophages. Therefore, these liposomes might be suitable for in vivo visualization of macrophage content and for (visualization of targeted drug delivery to inflammatory cells.

  16. 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.

  17. 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.

  18. Liposome disposition in vivo. VI: Delivery to the lung

    International Nuclear Information System (INIS)

    The effect of negatively charged liposome components and vesicle size on the time course and dose dependency of liposome disposition in mice was studied with a view to optimizing liposome delivery to the lung. The disposition of large multilamellar liposomes was followed using 125I-labeled p-hydroxybenzamidine phosphatidyl ethanolamine. Of the three negatively charged liposome compositions studied (phosphatidyl choline-X-cholesterol-alpha-tocopherol, molar ratio: 4:1:5:0.1; X . phosphatidyl serine, dipalmitoyl phosphatidic acid, or phosphatidyl glycerol), phosphatidyl serine liposomes resulted in the greatest accumulation in lungs. Lung levels decreased up to 95 h postdose, at which time 6% of the liposome dose present at 2 h still remained. The disposition of phosphatidyl serine-containing liposomes was independent of dose for the range 0.04-21 mumol/animal. When liposomes containing phosphatidyl choline were prepared using a variety of extrusion and dialysis conditions, a strong link between liposome size and lung accumulation was revealed. A maximum lung accumulation of 30.9% of the administered dose was achieved with no detectable gross pathological lung lesions up to 24 h postdose

  19. 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.

  20. Formation of Stable Cationic Lipid/DNA Complexes for Gene Transfer

    Science.gov (United States)

    Hofland, Hans E. J.; Shephard, Lee; Sullivan, Sean M.

    1996-07-01

    Stable cationic lipid/DNA complexes were formed by solubilizing cationic liposomes with 1% octylglucoside and complexing a DNA plasmid with the lipid in the presence of detergent. Removal of the detergent by dialysis yielded a lipid/DNA suspension that was able to transfect tissue culture cells up to 90 days after formation with no loss in activity. Similar levels of gene transfer were obtained by mixing the cationic lipid in a liposome form with DNA just prior to cell addition. However, expression was completely lost 24 hr after mixing. The transfection efficiency of the stable complex in 15% fetal calf serum was 30% of that obtained in the absence of serum, whereas the transient complex was completely inactivated with 2% fetal calf serum. A 90-day stability study comparing various storage conditions showed that the stable complex could be stored frozen or as a suspension at 4 degrees C with no loss in transfection efficiency. Centrifugation of the stable complex produced a pellet that contained approximately 90% of the DNA and 10% of the lipid. Transfection of cells with the resuspended pellet and the supernatant showed that the majority of the transfection activity was in the pellet and all the toxicity was in the supernatant. Formation of a stable cationic lipid/DNA complex has produced a transfection vehicle that can be stored indefinitely, can be concentrated with no loss in transfection efficiency, and the toxicity levels can be greatly reduced when the active complex is isolated from the uncomplexed lipid.

  1. The structure of Lactobacillus brevis surface layer reassembled on liposomes differs from native structure as revealed by SAXS.

    Science.gov (United States)

    Kontro, Inkeri; Wiedmer, Susanne K; Hynönen, Ulla; Penttilä, Paavo A; Palva, Airi; Serimaa, Ritva

    2014-08-01

    The reassembly of the S-layer protein SlpA of Lactobacillus brevis ATCC 8287 on positively charged liposomes was studied by small angle X-ray scattering (SAXS) and zeta potential measurements. SlpA was reassembled on unilamellar liposomes consisting of 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine and 1,2-dioleoyl-3-trimethylammonium-propane, prepared by extrusion through membranes with pore sizes of 50nm and 100nm. Similarly extruded samples without SlpA were used as a reference. The SlpA-containing samples showed clear diffraction peaks in their SAXS intensities. The lattice constants were calculated from the diffraction pattern and compared to those determined for SlpA on native cell wall fragments. Lattice constants for SlpA reassembled on liposomes (a=9.29nm, b=8.03nm, and γ=84.9°) showed a marked change in the lattice constants b and γ when compared to those determined for SlpA on native cell wall fragments (a=9.41nm, b=6.48nm, and γ=77.0°). The latter are in good agreement with values previously determined by electron microscopy. This indicates that the structure formed by SlpA is stable on the bacterial cell wall, but SlpA reassembles into a different structure on cationic liposomes. From the (10) reflection, the lower limit of crystallite size of SlpA on liposomes was determined to be 92nm, corresponding to approximately ten aligned lattice planes. PMID:24796504

  2. Synthesis and characterization of betaine-like diacyl lipids: zwitterionic lipids with the cationic amine at the bilayer interface.

    Science.gov (United States)

    Kohli, Aditya G; Walsh, Colin L; Szoka, Francis C

    2012-02-01

    We synthesized and characterized a series of zwitterionic, acetate-terminated, quaternized amine diacyl lipids (AQ). These lipids have an inverted headgroup orientation as compared to naturally occurring phosphatidylcholine (PC) lipids; the cationic group is anchored at the membrane interface, while the anionic group extends into the aqueous phase. AQ lipids preferentially interact with highly polarizable anions (ClO(4)(-)) over less polarizable ions (Cl(-)), in accord with the Hofmeister series, as measured by the change in zeta potential of AQ liposomes. Conversely, AQ lipids have a weaker association with calcium than do PC lipids. The transition temperatures (Tm) of the AQ lipids are similar to the Tm observed with phosphatidylethanolamine (PE) lipids of the same chain length. AQ lipids form large lipid sheets after heating and sonication; however, in the presence of cholesterol (Chol), these lipids form stable liposomes that encapsulate carboxyfluorescein. The AQ:Chol liposomes retain their contents in the presence of serum at 37°C, and when injected intravenously into mice, their organ biodistribution is similar to that observed with PC:Chol liposomes. AQ lipids demonstrate that modulating the headgroup charge orientation significantly alters the biophysical properties of liposomes. For the drug carrier field, these new materials provide a non-phosphate containing zwitterlipid for the production of lipid vesicles. PMID:22301334

  3. Formulation and in Vitro, ex Vivo and in Vivo Evaluation of Elastic Liposomes for Transdermal Delivery of Ketorolac Tromethamine

    Directory of Open Access Journals (Sweden)

    Néstor Mendoza

    2011-12-01

    Full Text Available The objective of the current study was to formulate ketorolac tromethamine-loaded elastic liposomes and evaluate their in vitro drug release and their ex vivo and in vivo transdermal delivery. Ketorolac tromethamine (KT, which is a potent analgesic, was formulated in elastic liposomes using Tween 80 as an edge activator. The elastic vesicles were prepared by film hydration after optimizing the sonication time and number of extrusions. The vesicles exhibited an entrapment efficiency of 73 ± 11%, vesicle size of 127.8 ± 3.4 nm and a zeta potential of −12 mV. In vitro drug release was analyzed from liposomes and an aqueous solution, using Franz diffusion cells and a cellophane dialysis membrane with molecular weight cut-off of 8000 Da. Ex vivo permeation of KT across pig ear skin was studied using a Franz diffusion cell, with phosphate buffer (pH 7.4 at 32 °C as receptor solution. An in vivo drug permeation study was conducted on healthy human volunteers using a tape-stripping technique. The in vitro results showed (i a delayed release when KT was included in elastic liposomes, compared to an aqueous solution of the drug; (ii a flux of 0.278 mg/cm2h and a lag time of about 10 h for ex vivo permeation studies, which may indicate that KT remains in the skin (with the possibility of exerting a local effect before reaching the receptor medium; (iii a good correlation between the total amount permeated, the penetration distance (both determined by tape stripping and transepidermal water loss (TEWL measured during the in vivo permeation studies. Elastic liposomes have the potential to transport the drug through the skin, keep their size and drug charge, and release the drug into deep skin layers. Therefore, elastic liposomes hold promise for the effective topical delivery of KT.

  4. Albumin coated liposomes: a novel platform for macrophage specific drug delivery

    OpenAIRE

    Clément Vuarchey; Sushil Kumar; Reto Schwendener

    2011-01-01

    Here we report a new and efficient approach of macrophage specific drug delivery by coating liposomes with albumin. Activated albumin was reacted with liposomes containing polyethylene glycol (PEG) as hydrophilic spacers to create a flexible layer of covalently bound albumin molecules on the liposome surface. Albumin coated liposomes were taken up faster and more efficiently than uncoated liposomes by murine macrophages. Liposome uptake was significantly higher in macropha - ges as compared t...

  5. Study on Leakage of Sesame (Sesamum indicum L.) and Coconut (Cocos nucifera L.) Liposomes

    OpenAIRE

    Dwi Hudiyanti; Tri Joko Raharjo; Narsito Narsito; Sri Noegrohati

    2015-01-01

    Leakage phenomena on sesame (Sesamum indicum L.) and coconut (Cocos nucifera L.) liposomes has been studied to evaluate their ability as drug delivery materials. Permeation of carboxyfluorescein through the liposomes with and without added cholesterol was examined. Sesame liposomes release carboxyfluorescein less than coconut liposomes in all circumstances. Sesame liposomes save about 50% of payload after 17 hours of storage while coconut liposomes only 10%. Addition of cholesterol has increa...

  6. Liposome-based drug delivery in breast cancer treatment

    International Nuclear Information System (INIS)

    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

  7. Enhanced oral bioavailability of silymarin using liposomes containing a bile salt: preparation by supercritical fluid technology and evaluation in vitro and in vivo.

    Science.gov (United States)

    Yang, Gang; Zhao, Yaping; Zhang, Yongtai; Dang, Beilei; Liu, Ying; Feng, Nianping

    2015-01-01

    The aim of this investigation was to develop a procedure to improve the dissolution and bioavailability of silymarin (SM) by using bile salt-containing liposomes that were prepared by supercritical fluid technology (ie, solution-enhanced dispersion by supercritical fluids [SEDS]). The process for the preparation of SM-loaded liposomes containing a bile salt (SM-Lip-SEDS) was optimized using a central composite design of response surface methodology with the ratio of SM to phospholipids (w/w), flow rate of solution (mL/min), and pressure (MPa) as independent variables. Particle size, entrapment efficiency (EE), and drug loading (DL) were dependent variables for optimization of the process and formulation variables. The particle size, zeta potential, EE, and DL of the optimized SM-Lip-SEDS were 160.5 nm, -62.3 mV, 91.4%, and 4.73%, respectively. Two other methods to produce SM liposomes were compared to the SEDS method. The liposomes obtained by the SEDS method exhibited the highest EE and DL, smallest particle size, and best stability compared to liposomes produced by the thin-film dispersion and reversed-phase evaporation methods. Compared to the SM powder, SM-Lip-SEDS showed increased in vitro drug release. The in vivo AUC(0-t) of SM-Lip-SEDS was 4.8-fold higher than that of the SM powder. These results illustrate that liposomes containing a bile salt can be used to enhance the oral bioavailability of SM and that supercritical fluid technology is suitable for the preparation of liposomes. PMID:26543366

  8. 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

  9. Microfluidic-Enabled Liposomes Elucidate Size-Dependent Transdermal Transport

    OpenAIRE

    Renee R Hood; Kendall, Eric L.; Junqueira, Mariana; Vreeland, Wyatt N.; Quezado, Zenaide; Julia C Finkel; DeVoe, Don L.

    2014-01-01

    Microfluidic synthesis of small and nearly-monodisperse liposomes is used to investigate the size-dependent passive transdermal transport of nanoscale lipid vesicles. While large liposomes with diameters above 105 nm are found to be excluded from deeper skin layers past the stratum corneum, the primary barrier to nanoparticle transport, liposomes with mean diameters between 31–41 nm exhibit significantly enhanced penetration. Furthermore, multicolor fluorescence imaging reveals that the small...

  10. [Novel possibilities of development and therapeutical application of liposomes].

    Science.gov (United States)

    Bozó, Tamás; Pál, Szilárd; Dévay, Attila

    2008-01-01

    Properties and possibilities of application of liposomal drug delivery systems are summarized in this review. Technological and biopharmeceutical criteria that have to be taken into consideration in the course of development of biocompatible liposomes are discussed. The manner and possibilities of active and passive targeting are shown according to the literary data and special liposome-based drug delivery systems responsible for pathologic or arteficial stimuli are introduced. PMID:18986087

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

    OpenAIRE

    Mady, Mohsen M; Mirhane M. Darwish

    2010-01-01

    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 con...

  12. Increased Liposome Extravasation in Selected Tissues: Effect of Substance P

    Science.gov (United States)

    Rosenecker, Joseph; Zhang, Weiming; Hong, Keelung; Lausier, James; Geppetti, Pierangelo; Yoshihara, Shigemi; Papahadjopoulos, Demetrios; Nadel, Jay A.

    1996-07-01

    We have used a pharmacologic mediator to open intercellular connections in selected vessels to allow liposomes to escape from the blood stream and to extravasate into tissues that have appropriate receptors. We have examined the effects of substance P (SP), a peptide known to increase vascular permeability in selected tissues, such as trachea, esophagus, and urinary bladder in rats. We used quantitative fluorescence analysis of tissues to measure two fluorescent markers, one attached to the lipid (rhodamine-phosphatidylethanolamine) and another, doxorubicin (an antitumor drug), encapsulated within the aqueous interior. We have also examined the deposition of liposomes microscopically by the use of encapsulated colloidal gold and silver enhancement. Analysis of the biochemical and morphological observations indicate the following: (i) Injection of SP produces a striking increase in both liposome labels, but only in tissues that possess receptors for SP in postcapillary venules; (ii) liposome material in these tissues has extravasated and is found extracellularly near a variety of cells beyond the endothelial layer over the first few hours; (iii) 24 h following injection of liposomes and SP, liposome material is found in these tissues, localized intracellularly in both endothelial cells and macrophages. We propose that appropriate application of tissue-specific mediators can result in liposome extravasation deep within tissues that normally do not take up significant amounts of liposomes from the blood. Such liposomes are able to carry a variety of pharmacological agents that can be released locally within selected target tissues for therapeutic purposes.

  13. Analyzing Protein-Phosphoinositide Interactions with Liposome Flotation Assays.

    Science.gov (United States)

    Busse, Ricarda A; Scacioc, Andreea; Schalk, Amanda M; Krick, Roswitha; Thumm, Michael; Kühnel, Karin

    2016-01-01

    Liposome flotation assays are a convenient tool to study protein-phosphoinositide interactions. Working with liposomes resembles physiological conditions more than protein-lipid overlay assays, which makes this method less prone to detect false positive interactions. However, liposome lipid composition must be well-considered in order to prevent nonspecific binding of the protein through electrostatic interactions with negatively charged lipids like phosphatidylserine. In this protocol we use the PROPPIN Hsv2 (homologous with swollen vacuole phenotype 2) as an example to demonstrate the influence of liposome lipid composition on binding and show how phosphoinositide binding specificities of a protein can be characterized with this method. PMID:26552682

  14. Application of long-circulating liposomes to cancer photodynamic therapy.

    Science.gov (United States)

    Oku, N; Saito, N; Namba, Y; Tsukada, H; Dolphin, D; Okada, S

    1997-06-01

    Photodynamic therapy (PDT) as a cancer treatment is notable for its quite low side effects in comparison with those of chemotherapy and radiotherapy. However, the accumulation of porphyrin derivatives used in PDT into tumor tissues is rather low. Since long-circulating liposomes are known to accumulate passively into tumor tissues, we liposomalized a porphyrin derivative, benzoporphyrin derivative monoacid ring A (BPD-MA), and used these liposomes to investigate the usefulness of PDT for tumor-bearing mice. BPD-MA was liposomalized into glucuronate-modified liposomes, which are known to be long-circulating. These liposomes were injected i.v. into Balb/c mice bearing Meth A sarcoma, and tumor regression and survival time were monitored after irradiation with laser light. Tumor regression and complete curing of tumor (80% cure rate by the treatment with 6 mg/kg BPD-MA) were observed when long circulating liposomalized BPD-MA was injected and laser-irradiated. In contrast, only a 20% cure rate was obtained when the animals were treated with BPD-MA solution or BPD-MA entrapped in conventional liposomes. These results suggest that a long-circulating liposomal formulation of photo-sensitive agents is useful for PDT. PMID:9212988

  15. Tumor targeting using liposomal antineoplastic drugs

    OpenAIRE

    Jörg Huwyler; Jürgen Drewe; Stephan Krähenbühl

    2008-01-01

    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 applicatio...

  16. PREPARATION OF LIPOSOMES CONTAINING WHEY PROTEINS

    OpenAIRE

    A. Suha Yalçın; Murat Türkoğlu

    2010-01-01

    Aim: In recent years, it has been shown that whey and its components have a number of health-promoting effects. We aimed to isolate fractions containing whey proteins using chromatography and then to prepare antioxidant liposomes in order to obtain a gel suitable for cosmetic preparations.Methods: Fractionation of whey proteins was achieved by extraction, filtration and centrifugation followed by liquid chromatography. The antioxidant activities of the fractions was determined by their copper...

  17. Nitric oxide pretreatment enhances atheroma component highlighting in vivo with intercellular adhesion molecule-1-targeted echogenic liposomes.

    Science.gov (United States)

    Kee, Patrick H; Kim, Hyunggun; Huang, Shaoling; Laing, Susan T; Moody, Melanie R; Vela, Deborah; Klegerman, Melvin E; McPherson, David D

    2014-06-01

    We present an ultrasound technique for the detection of inflammatory changes in developing atheromas. We used contrast-enhanced ultrasound imaging with (i) microbubbles targeted to intercellular adhesion molecule-1 (ICAM-1), a molecule of adhesion involved in inflammatory processes in lesions of atheromas in New Zealand White rabbits, and (ii) pretreatment with nitric oxide-loaded microbubbles and ultrasound activation at the site of the endothelium to enhance the permeability of the arterial wall and the penetration of ICAM-1-targeted microbubbles. This procedure increases acoustic enhancement 1.2-fold. Pretreatment with nitric oxide-loaded echogenic liposomes and ultrasound activation can potentially facilitate the subsequent penetration of targeted echogenic liposomes into the arterial wall, thus allowing improved detection of inflammatory changes in developing atheromas. PMID:24613216

  18. Comparison of ethosomes and liposomes for skin delivery of psoralen for psoriasis therapy.

    Science.gov (United States)

    Zhang, Yong-Tai; Shen, Li-Na; Wu, Zhong-Hua; Zhao, Ji-Hui; Feng, Nian-Ping

    2014-08-25

    Recent reports have indicated that psoriasis may be caused by malfunctioning dermal immune cells, and psoralen ultraviolet A (PUVA) is an effective treatment for this chronic disease. However, conventional topical formulations achieve poor drug delivery across patches of psoriasis to their target sites. The present study describes the development of a novel psoralen transdermal delivery system employing ethosomes, flexible vesicles that can penetrate the stratum corneum and target deep skin layers. An in vitro skin permeation study showed that the permeability of psoralen-loaded ethosomes was superior to that of liposomes. Using ethosomes, psoralen transdermal flux and skin deposition were 38.89±0.32 μg/cm(2)/h and 3.87±1.74 μg/cm(2), respectively, 3.50 and 2.15 times those achieved using liposomes, respectively. The ethosomes and liposomes were found to be safe following daily application to rat skin in vivo, for 7 days. The ethosomes showed better biocompatibility with human embryonic skin fibroblasts than did an equivalent ethanol solution, indicating that the phosphatidylcholine present in ethosome vesicles improved their biocompatibility. These findings indicated that ethosomes could potentially improve the dermal and transdermal delivery of psoralen and possibly of other drugs requiring deep skin delivery. PMID:24907596

  19. Ganoderma lucidum polysaccharides encapsulated in liposome as an adjuvant to promote Th1-bias immune response.

    Science.gov (United States)

    Liu, Zhenguang; Xing, Jie; Zheng, Sisi; Bo, Ruonan; Luo, Li; Huang, Yee; Niu, Yale; Li, Zhihua; Wang, Deyun; Hu, Yuanliang; Liu, Jiaguo; Wu, Yi

    2016-05-20

    Liposome-based vaccine delivery systems are known to enhance immune responses. Ganoderma lucidum polysaccharides (GLP) have been widely studied as immunomodulator and it could be as inducers of strong immune responses. In the research, GLP and ovalbumin (OVA) were encapsulated into liposome as vaccine and inoculated to mice. The magnitude and kinetics of the humoral and cellular immune responses were investigated. The results showed that GLP-OVA-loaded liposomes (GLPL/OVA) could induce more powerful antigen-specific immune responses than each single-component formulation. Mice immunized with GLPL/OVA displayed higher antigen-specific IgG antibodies, better splenocytes proliferation, higher cytokine secretion by splenocytes and significant activation of CD3+CD4+ and CD3+CD8+ T cells. Thus the GLPL/OVA formulation produced a heightened humoral and cellular immune response, with an overall Th1 bias. Enhanced immune responses elicited by the GLPL/OVA formulation might be attributed to effective activation and mature of DC in draining lymph nodes. Overall, these findings indicate that GLPL have the potential to enhance immune responses as vaccine delivery systems. PMID:26917384

  20. Enhanced oral bioavailability and in vivo antioxidant activity of chlorogenic acid via liposomal formulation.

    Science.gov (United States)

    Feng, Yingshu; Sun, Congyong; Yuan, Yangyang; Zhu, Yuan; Wan, Jinyi; Firempong, Caleb Kesse; Omari-Siaw, Emmanuel; Xu, Yang; Pu, Zunqin; Yu, Jiangnan; Xu, Ximing

    2016-03-30

    In the present study, a formulation system consisting of cholesterol and phosphatidyl choline was used to prepare an effective chlorogenic acid-loaded liposome (CAL) with an improved oral bioavailability and an increased antioxidant activity. The developed liposomal formulation produced regular, spherical and multilamellar-shaped distribution nanoparticles. The pharmacokinetic analysis of CAL compared with chlorogenic acid (CA), showed a higher value of Cmax(6.42 ± 1.49 min versus 3.97 ± 0.39 min) and a delayed Tmax(15 min versus 10 min), with 1.29-fold increase in relative oral bioavailability. The tissue distribution in mice also demonstrated that CAL predominantly accumulated in the liver which indicated hepatic targeting potential of the drug. The increased activities of antioxidant enzymes (Total Superoxide Dismutase (T-SOD) and Glutathione Peroxidase (GSH-Px)) and total antioxidant capacity (T-AOC), in addition to decreased level of malondialdehyde (MDA) in CCl4-induced hepatotoxicity study further revealed that CAL exhibited significant hepatoprotective and antioxidant effects. Collectively, these findings present a liposomal formulation with significantly improved oral bioavailability and an increased in vivo antioxidant activity of CA. PMID:26861689

  1. The potential use of novel chitosan-coated deformable liposomes in an ocular drug delivery system.

    Science.gov (United States)

    Chen, Hongdan; Pan, Hao; Li, Panpan; Wang, Hui; Wang, Xin; Pan, Weisan; Yuan, Yue

    2016-07-01

    In this study, novel chitosan-coated deformable liposomes (DL-CS) were proposed as an ocular drug delivery system to prolong pre-corneal retention, and improve transcorneal penetration and absorption. Flurbiprofen-loaded deformable liposomes (FP-DL) were prepared by a modified ethanol injection method and then coated with chitosan. Both DL and DL-CS exhibited a homogeneous particle size distribution, high encapsulation efficiency and good stability. After coating with 0.1% CS, the zeta potential was shifted from negative to positive. The apparent permeability coefficient of FP-DL-0.1% CS evaluated using isolated rabbit corneas was 1.29-, 1.95- and 4.59- fold greater than that of uncoated FP-DL, conventional liposomes and FP solution (P<0.01), respectively. The in vivo pre-corneal retention time and elimination dynamics were assessed using gamma scintigraphy technology. The area under the remaining activity-time of FP-DL-0.1% CS was prolonged 2.84- and 1.53-fold compared with that of the FP solution and FP-DL groups, respectively. Moreover, the ocular irritation test in vivo revealed that DL-0.1% CS produced no ocular damage or abnormal clinical signs. These results indicate that DL-CS appears to be a novel ophthalmic drug delivery strategy with the potential to overcome the limitations of conventional eye drops. PMID:27037783

  2. A Combination of Targeted Sunitinib Liposomes and Targeted Vinorelbine Liposomes for Treating Invasive Breast Cancer.

    Science.gov (United States)

    Shi, Ji-Feng; Sun, Meng-Ge; Li, Xiu-Ying; Zhao, Yao; Ju, Rui-Jun; Mu, Li-Min; Yan, Yan; Li, Xue-Tao; Zeng, Fan; Lu, Wan-Liang

    2015-09-01

    Regular chemotherapy cannot eradicate invasive breast cancer cells and the residual cancer cells will form vasculogenic mimicry (VM) channels under hypoxic conditions to provide nutrients for cancer masses prior to angiogenesis. This phenomenon is a major reason for the recurrence of invasive breast cancer after treatment. In this study, a novel type of targeted liposomes was developed by modifying a mitochondria-tropic material, D-a-tocopheryl polyethylene glycol 1000 succinate- triphenylphosphine conjugate (TPGS1000-TPP), to encapsulate sunitinib and vinorelbine separately and a combination of the two targeted drug liposomes was used to treat invasive breast cancer as well as VM channels. Evaluations were performed in breast cancer MCF-7 cells and highly invasive breast cancer MDA-MB-435S cells in vitro and in mice. The results determined that the functional material (TPGS1000-TPP) and suitable size of the liposomes (90-100 nm) resulted in prolonged blood circulation, an enhanced permeability retention (EPR) effect in cancer tissue, and a mitochondrial targeting effect. Targeted drug liposomes were internalized via cellular uptake and accumulated in the mitochondria of invasive breast cancer cells or VM channel-forming cancer cells to induce acute cytotoxic injury and apoptosis. Activated apoptotic enzymes caspase 9 and caspase 3 as well as down-regulated VM channel-forming indicators (MMP-9, EphA2, VE-Cadherin, FAK and HIF-1α) contributed to significantly enhanced efficacy. Therefore, a combination of targeted sunitinib liposomes and targeted vinorelbine liposomes may provide an effective strategy for treating invasive breast cancer and prevent relapse arising from VM channels. PMID:26485927

  3. Reversal of multidrug resistance by co-delivery of paclitaxel and lonidamine using a TPGS and hyaluronic acid dual-functionalized liposome for cancer treatment.

    Science.gov (United States)

    Assanhou, Assogba G; Li, Wenyuan; Zhang, Lei; Xue, Lingjing; Kong, Lingyi; Sun, Hongbin; Mo, Ran; Zhang, Can

    2015-12-01

    Multidrug resistance (MDR) remains the primary issue in cancer therapy, which is characterized by the overexpressed P-glycoprotein (P-gp)-included efflux pump or the upregulated anti-apoptotic proteins. In this study, a D-alpha-tocopheryl poly (ethylene glycol 1000) succinate (TPGS) and hyaluronic acid (HA) dual-functionalized cationic liposome containing a synthetic cationic lipid, 1,5-dioctadecyl-N-histidyl-L-glutamate (HG2C18) was developed for co-delivery of a small-molecule chemotherapeutic drug, paclitaxel (PTX) with a chemosensitizing agent, lonidamine (LND) to treat the MDR cancer. It was demonstrated that the HG2C18 lipid contributes to the endo-lysosomal escape of the liposome following internalization for efficient intracellular delivery. The TPGS component was confirmed able to elevate the intracellular accumulation of PTX by inhibiting the P-gp efflux, and to facilitate the mitochondrial-targeting of the liposome. The intracellularly released LND suppressed the intracellular ATP production by interfering with the mitochondrial function for enhanced P-gp inhibition, and additionally, sensitized the MDR breast cancer (MCF-7/MDR) cells to PTX for promoted induction of apoptosis through a synergistic effect. Functionalized with the outer HA shell, the liposome preferentially accumulated at the tumor site and showed a superior antitumor efficacy in the xenograft MCF-7/MDR tumor mice models. These findings suggest that this dual-functional liposome for co-delivery of a cytotoxic drug and an MDR modulator provides a promising strategy for reversal of MDR in cancer treatment. PMID:26426537

  4. Nanodrug-Enhanced Radiofrequency Tumor Ablation: Effect of Micellar or Liposomal Carrier on Drug Delivery and Treatment Efficacy

    OpenAIRE

    Moussa, Marwan; Goldberg, S. Nahum; Kumar, Gaurav; Sawant, Rupa R.; Levchenko, Tatyana; Torchilin, Vladimir P.; Ahmed, Muneeb

    2014-01-01

    Purpose To determine the effect of different drug-loaded nanocarriers (micelles and liposomes) on delivery and treatment efficacy for radiofrequency ablation (RFA) combined with nanodrugs. Materials/Methods Fischer 344 rats were used (n = 196). First, single subcutaneous R3230 tumors or normal liver underwent RFA followed by immediate administration of IV fluorescent beads (20, 100, and 500 nm), with fluorescent intensity measured at 4–24 hr. Next, to study carrier type on drug efficiency, RF...

  5. Nanodrug-Enhanced Radiofrequency Tumor Ablation: Effect of Micellar or Liposomal Carrier on Drug Delivery and Treatment Efficacy

    OpenAIRE

    Marwan Moussa; S Nahum Goldberg; Gaurav Kumar; Sawant, Rupa R.; Tatyana Levchenko; Torchilin, Vladimir P.; Muneeb Ahmed

    2014-01-01

    PURPOSE: To determine the effect of different drug-loaded nanocarriers (micelles and liposomes) on delivery and treatment efficacy for radiofrequency ablation (RFA) combined with nanodrugs. MATERIALS/METHODS: 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...

  6. 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

  7. Positron Emission Tomography Based Elucidation of the Enhanced Permeability and Retention Effect in Dogs with Cancer Using Copper-64 Liposomes.

    Science.gov (United States)

    Hansen, Anders E; Petersen, Anncatrine L; Henriksen, Jonas R; Boerresen, Betina; Rasmussen, Palle; Elema, Dennis R; Rosenschöld, Per Munck af; Kristensen, Annemarie T; Kjær, Andreas; Andresen, Thomas L

    2015-07-28

    Since the first report of the enhanced permeability and retention (EPR) effect, the research in nanocarrier based antitumor drugs has been intense. The field has been devoted to treatment of cancer by exploiting EPR-based accumulation of nanocarriers in solid tumors, which for many years was considered to be a ubiquitous phenomenon. However, the understanding of differences in the EPR-effect between tumor types, heterogeneities within each patient group, and dependency on tumor development stage in humans is sparse. It is therefore important to enhance our understanding of the EPR-effect in large animals and humans with spontaneously developed cancer. In the present paper, we describe a novel loading method of copper-64 into PEGylated liposomes and use these liposomes to evaluate the EPR-effect in 11 canine cancer patients with spontaneous solid tumors by PET/CT imaging. We thereby provide the first high-resolution analysis of EPR-based tumor accumulation in large animals. We find that the EPR-effect is strong in some tumor types but cannot be considered a general feature of solid malignant tumors since we observed a high degree of accumulation heterogeneity between tumors. Six of seven included carcinomas displayed high uptake levels of liposomes, whereas one of four sarcomas displayed signs of liposome retention. We conclude that nanocarrier-radiotracers could be important in identifying cancer patients that will benefit from nanocarrier-based therapeutics in clinical practice. PMID:26022907

  8. Cationic Antimicrobial Peptide Cytotoxicity

    OpenAIRE

    Laverty, Garry; Gilmore, Brendan

    2014-01-01

    Fluorescence microscopy serves as a valuable tool for assessing the structural integrity and viability of eukaryotic cells. Through the use of calcein AM and the DNA stain 4,6-diamidino-2 phenylindole (DAPI), cell viability and membrane integrity can be qualified. Our group has previously shown the ultra-short cationic antimicrobial peptide H-OOWW-NH2; the amphibian derived 27-mer peptide Maximin-4and the ultra-short lipopeptide C12-OOWW-NH2 to be effective against a range of bacterial biofil...

  9. Efficient downregulation of VEGF in retinal pigment epithelial cells by integrin ligand-labeled liposome-mediated siRNA delivery

    Directory of Open Access Journals (Sweden)

    Chen C

    2013-07-01

    Full Text Available Cheng-Wei Chen,1 Ming-Kung Yeh,2 Chia-Yang Shiau,3 Chiao-Hsi Chiang,4,* Da-Wen Lu5,*1Chengwei Biotechnology Co, Ltd, 2Bureau of Pharmaceutical Affairs, Military of National Defense Medical Affairs Bureau, 3Graduate Institute of Medical Sciences, 4School of Pharmacy, National Defense Medical Center, 5Department of Ophthalmology, Tri-Service General Hospital, Taipei, Taiwan *These authors contributed equally to this workBackground: The purpose of this study was to demonstrate the effectiveness of an integrin peptide ligand-labeled liposomal delivery system loaded with vascular endothelial growth factor (VEGF-siRNA in a model study of gene therapy for retinopathy using human retinal pigment epithelial cells.Methods: Arg(R-Gly(G-Asp(D motif peptide conjugating polyethylene glycol modified (RGD-PEGylated liposomes were prepared using a thin-film hydration method and optimized for surface charge, particle size, small interfering RNA (siRNA load, and entrapment efficiency. Reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assays were used to determine VEGF levels in retinal pigment epithelial cells. Cytotoxicity was determined using the 3-[4, 5-dimethylthiazol-2-yl]-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium (MTS assay and flow cytometry.Results: Physicochemical properties, including particle size, zeta potential, and siRNA load, of the prepared RGD-PEGylated liposomes and their entrapment efficiency were determined to be within the following ranges: 123.8–234.1 nm, 17.31–40.09 mV, 5.27%–6.33%, and >97%, respectively. RGD-PEGylated liposome-mediated fluorescent-labeled siRNA delivery demonstrated significantly enhanced cellular uptake, and 3 mol% RGD-PEGylated liposomes (having 3β-[N-(N´, N´-dimethylaminoethane carbamoyl] cholesterol (DC-cholesterol DSPE and DSPE-PEG(2000-RGD with molar ratio of 50/47/3 were shown to have better efficacy with regard to specificity for retinal pigment epithelial

  10. Preparation and characterization of gas-filled liposomes: can they improve oil recovery?

    Science.gov (United States)

    Vangala, Anil; Morris, Robert; Bencsik, Martin; Perrie, Yvonne

    2007-01-01

    Although well known for delivering various pharmaceutical agents, liposomes can be prepared to entrap gas rather than aqueous media and have the potential to be used as pressure probes in magnetic resonance imaging (MRI). Using these gas-filled liposomes (GFL) as tracers, MRI imaging of pressure regions of a fluid flowing through a porous medium could be established. This knowledge can be exploited to enhance recovery of oil from the porous rock regions within oil fields. In the preliminary studies, we have optimized the lipid composition of GFL prepared using a simple homogenization technique and investigated key physico-chemical characteristics (size and the physical stability) and their efficacy as pressure probes. In contrast to the liposomes possessing an aqueous core which are prepared at temperatures above their phase transition temperature (T(c)), homogenization of the phospholipids such as 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or 1,2-distearoyl-sn-glycero-3-phosphocoline (DSPC) in aqueous medium below their T(c) was found to be crucial in formation of stable GFL. DSPC based preparations yielded a GFL volume of more than five times compared to their DPPC counter part. Although the initial vesicle sizes of both DSPC and DPPC based GFL were about 10 microm, after 7 days storage at 25 degrees C, the vesicle sizes of both formulations significantly (p surfactant, stearylamine, at a molar ratio of 0.25 or 0.125. Interestingly, the zeta potential values remained around neutrality at both stearylamine ratios suggesting the cationic surfactant was not incorporated within the bilayers of the GFL. Microscopic analysis of GFL confirmed the presence of spherical structures with a size distribution between 1-8 microm. This study has identified that DSPC based GFL in aqueous medium dispersed in 2% w/v methyl cellulose although yielded higher vesicle sizes over time were most stable under high pressures exerted in MRI. PMID:18027246

  11. The clearance of liposomes administered by the intramuscular route

    International Nuclear Information System (INIS)

    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.)

  12. Liposomal budesonide for dry powder inhaler: Preparation and stabilization

    OpenAIRE

    Joshi, Mayank R.; Misra, Ambikanandhan

    2001-01-01

    The purpose of the study was to prepare stable liposomally entrapped budesonide (BUD) for a dry powder inhaler (DPI) formulation. BUD liposomes composed of egg phosphatidyl choline and cholesterol were prepared by lipid film hydration technique and sonicated to have the desired size (

  13. Immunological Effect of Subunit Influenza Vaccine Entrapped by Liposomes

    Institute of Scientific and Technical Information of China (English)

    SHUI-HUA ZHANG; JIA-XU LIANG; SHU-YAN DAI; XIAO-LIN QIU; YAN-RONG YI; YUN PAN

    2009-01-01

    Objective To elevate the immunological effect of subunit influenza vaccine in infants and aged people (over 60) using liposomal adjuvant in the context of its relatively low immunity and to investigate the relation between vaccine antigens and liposomal characteristics. Methods Several formulations of liposomal subunit influenza vaccine were prepared. Their relevant characteristics were investigated to optimize the preparation method. Antisera obtained from immunizinged mice were used to evaluate the antibody titers of various samples by HI and ELISA. Results Liposomal trivalent influenza vaccine prepared by film evaporation in combinedation with freeze-drying significantly increased its immunological effect in SPF Balb/c mice. Liposomal vaccine stimulated the antibody titer of H3N2, H1N1, and B much stronger than conventional influenza vaccine. As a result, liposomal vaccine (mean size: 4.5-5.5 μm, entrapment efficiency: 30%-40%) significantly increased the immunological effect of subunit influenza vaccine. Conclusion The immune effect of liposomal vaccine depends on different antigens, and enhanced immunity is not positively correlated with the mean size of liposome or its entrapped efficiency.

  14. Current Trends in Development of Liposomes for Targeting Bacterial Biofilms

    OpenAIRE

    Zora Rukavina; Željka Vanić

    2016-01-01

    Biofilm targeting represents a great challenge for effective antimicrobial therapy. Increased biofilm resistance, even with the elevated concentrations of very potent antimicrobial agents, often leads to failed therapeutic outcome. Application of biocompatible nanomicrobials, particularly liposomally-associated nanomicrobials, presents a promising approach for improved drug delivery to bacterial cells and biofilms. Versatile manipulations of liposomal physicochemical properties, such as the b...

  15. Encapsulation of antitumor drug methotrexate in liposome vesicles

    International Nuclear Information System (INIS)

    Liposome vesicles containing antitumor drug methotrexate (MTX) were prepared. MTX was labelled by the tritium ion beam method. After purification by TLC, the specific radioactivity of 3H-MTX was 1.19 GBq/mmol with radiochemical purity orver 95%. Under various forming conditions of liposome vesicles, the efficiency of encapsulation was 21-53%

  16. Application of liposome-encapsulated ceramic phoshpors for cancer cell imaging under near infrared excitation

    International Nuclear Information System (INIS)

    Bioimaging with fluorescent probes is used as an invaluable tool in a biomedical field both in vivo and in vitro. However, organic dyes have some problems such as photo-breaching and cytotoxicity due to short wavelength with high quantum energy. Recently, a new approach using rare-earth-doped ceramic nanophosphors (RED-CNP) shows that fluorescence from RED-CNP in both visible (upconversion) and near infrared (NIR) wavelength region under NIR excitation is available for bioimaging. In order to efficiently introduce the RED-CNP into cancer cells, in this study we have developed a lipid nano-particles of liposome-encapsulated erbium (Er) ion-doped Y2O3 (lipo-Y2O3). Cationic lipo-Y2O3 could clearly visualize the intracellular region of human hepatocellular carcinoma Huh-7 cells by a fluorescence microscope measurements equipped with near-infrared excitation source scanning. The results imply that the lipo-Y2O3 would potentially be useful material for imaging of cancer cells. The embedded Y2O3 in the liposome having cancer-specific ligands and/or antibodies on its surface should have a great potential for cancer cell imaging in general in living subjects.

  17. Triphenylphosphonium Decorated Liposomes and Dendritic Polymers: Prospective Second Generation Drug Delivery Systems for Targeting Mitochondria.

    Science.gov (United States)

    Paleos, Constantinos M; Tsiourvas, Dimitris; Sideratou, Zili

    2016-07-01

    Targeting specific intracellular organelles has been a biological process of significant interest. Specifically, for mitochondrial targeting, conventional liposomal and dendritic polymer nanoparticles were selected to be presented in this miniperspective. Both types of nanoparticles were decorated on their external surface with triphenylphosphonium cation (TPP), a well-known and effective mitochondrial targeting moiety. Due to their advantageous specificity toward mitochondria, these nanoparticles may be considered as prospective second generation drug delivery systems (DDSs). Functionalized liposomal and dendritic nanoparticles are conveniently prepared, and although they encounter several hurdles on their route from the extracellular environment to the interior of mitochondria, they manage to be accumulated inside them in experiments in vitro. Therefore, the TPP-functionalized nanoparticles presented in this miniperspective can prove effective DDSs and efforts should be continued to obtain results that will trigger further studies including clinical studies, hopefully leading to effective drugs for mitochondrial diseases. In fact, since these DDSs enter and act at the site where the dysfunction exists, a new medicine subspecialty is emerging, the so-called mitochondrial medicine. PMID:27280339

  18. Application of liposome-encapsulated ceramic phoshpors for cancer cell imaging under near infrared excitation

    Energy Technology Data Exchange (ETDEWEB)

    Akiyama, Hirotada; Otsuka, Hiroko; Tashiro, Fumio [Department of Biological Science and Technology, Tokyo University of Science (Japan); Tokuzen, Kimikazu; Soga, Kohei, E-mail: hakiyama@rs.noda.tus.ac.j [Polyscale Technology Research Center, Tokyo University of Science (Japan)

    2010-06-01

    Bioimaging with fluorescent probes is used as an invaluable tool in a biomedical field both in vivo and in vitro. However, organic dyes have some problems such as photo-breaching and cytotoxicity due to short wavelength with high quantum energy. Recently, a new approach using rare-earth-doped ceramic nanophosphors (RED-CNP) shows that fluorescence from RED-CNP in both visible (upconversion) and near infrared (NIR) wavelength region under NIR excitation is available for bioimaging. In order to efficiently introduce the RED-CNP into cancer cells, in this study we have developed a lipid nano-particles of liposome-encapsulated erbium (Er) ion-doped Y{sub 2}O{sub 3} (lipo-Y{sub 2}O{sub 3}). Cationic lipo-Y{sub 2}O{sub 3} could clearly visualize the intracellular region of human hepatocellular carcinoma Huh-7 cells by a fluorescence microscope measurements equipped with near-infrared excitation source scanning. The results imply that the lipo-Y{sub 2}O{sub 3} would potentially be useful material for imaging of cancer cells. The embedded Y{sub 2}O{sub 3} in the liposome having cancer-specific ligands and/or antibodies on its surface should have a great potential for cancer cell imaging in general in living subjects.

  19. Characteristics of photosensitization of Pheophorbide a in liposomal media

    Institute of Scientific and Technical Information of China (English)

    杨红英; 李美芬; 张文庚; 赵红霞; 张志义

    1999-01-01

    Pheophorbide a (PPa), a decomposition product of chlorophyll a, is a photosensitizer. The photosensitization mechanisms (Type Ⅰ and Type Ⅱ) of PPa in simple buffer solutions and in buffer solutions containing double-layered DPPC liposomes have been studied using techniques of ESR, spin-trapping, spin-counteraction and laser flash photolysis. The results showed that adding DPPC liposomes to the buffer solution caused an increase of efficiency of generating 1O2 and PPa- by photoactivating PPa. The increase could be ascribed to the disaggregation of hydrophobic PPa caused by the addition of liposomes and the protective effect of liposomal media on the triplet state of PPa. It is concluded that the photosensitization of PPa in liposomal systems is different from that in simple aqueous solutions, and shows higher efficacy. The results will be useful to elucidating the mechanisms of photodynamic therapy of cancer.

  20. 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.

  1. Current Trends in Development of Liposomes for Targeting Bacterial Biofilms.

    Science.gov (United States)

    Rukavina, Zora; Vanić, Željka

    2016-01-01

    Biofilm targeting represents a great challenge for effective antimicrobial therapy. Increased biofilm resistance, even with the elevated concentrations of very potent antimicrobial agents, often leads to failed therapeutic outcome. Application of biocompatible nanomicrobials, particularly liposomally-associated nanomicrobials, presents a promising approach for improved drug delivery to bacterial cells and biofilms. Versatile manipulations of liposomal physicochemical properties, such as the bilayer composition, membrane fluidity, size, surface charge and coating, enable development of liposomes with desired pharmacokinetic and pharmacodynamic profiles. This review attempts to provide an unbiased overview of investigations of liposomes destined to treat bacterial biofilms. Different strategies including the recent advancements in liposomal design aiming at eradication of existing biofilms and prevention of biofilm formation, as well as respective limitations, are discussed in more details. PMID:27231933

  2. Shrinkage of pegylated and non-pegylated liposomes in serum.

    Science.gov (United States)

    Wolfram, Joy; Suri, Krishna; Yang, Yong; Shen, Jianliang; Celia, Christian; Fresta, Massimo; Zhao, Yuliang; Shen, Haifa; Ferrari, Mauro

    2014-02-01

    An essential requisite for the design of nanodelivery systems is the ability to characterize the size, homogeneity and zeta potential of nanoparticles. Such properties can be tailored in order to create the most efficient drug delivery platforms. An important question is whether these characteristics change upon systemic injection. Here, we have studied the behavior of phosphatidylcholine/cholesterol liposomes exposed to serum proteins. The results reveal a serum-induced reduction in the size and homogeneity of both pegylated and non-pegylated liposomes, implicating the possible role of osmotic forces. In addition, changes to zeta-potential were observed upon exposing liposomes to serum. The liposomes with polyethylene glycol expressed different characteristics than their non-polymeric counterparts, suggesting the potential formation of a denser protein corona around the non-pegylated liposomes. PMID:24216620

  3. 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.

  4. 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.

  5. Loading technique for preparing radionuclide containing nanoparticles

    DEFF Research Database (Denmark)

    2011-01-01

    Source: US2012213698A The present invention relates to a novel composition and method for loading delivery systems such as liposome compositions with radionuclides useful in targeted diagnostic and/or therapy of target site, such as cancerous tissue and, in general, pathological conditions associ...... of positron emission tomography (PET) imaging technique. One specific aspect of the invention is directed to a method of producing nanoparticles with desired targeting properties for diagnostic and/or radio-therapeutic applications....

  6. A Liposomal Formulation Able to Incorporate a High Content of Paclitaxel and Exert Promising Anticancer Effect

    OpenAIRE

    Pei Kan; Chih-Wan Tsao; Ae-June Wang; Wu-Chou Su; Hsiang-Fa Liang

    2011-01-01

    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 o...

  7. Image-Guided Predictions of Liposome Transport in Solid Tumours

    Science.gov (United States)

    Stapleton, Shawn

    Due to the ability to preferentially accumulate and deliver drug payloads to solid tumours, liposomes have emerged as an exciting therapeutic strategy for cancer therapy. Unfortunately, the initial excitement was dampened by limited clinical results, where only negligible increases in patient survival following liposome therapy have been observed. What are the reasons for the limited clinical efficacy? Is the nanoparticle formulation optimal? Is the enhanced permeability and retention effect overstated? What are the barriers limiting the delivery of drugs to cancer cells? What is the optimal dosing and treatment schedule? Addressing these questions requires developing quantitative tools to understand the behaviour of liposomes in vivo, such as pharmacokinetics, biodistribution, intra-tumoural accumulation, and drug release. Central to each of these questions is the concept of transport - the collection of biophysical processes responsible for the delivery of molecules to tissues. Understanding transport means understanding the crucial links between the spatio-temporal accumulation of liposomes, the physicochemical properties of liposomes, and properties of the tumour microenvironment. In this thesis, a biophysical mathematical transport model is developed that when used in combination with non-invasive imaging methods can predict liposome transport in solid tumours. The mathematical transport framework is validated in its ability to predict the bulk and intra-tumoural accumulation of liposomes based on biophysical transport properties of solid tumours. Furthermore, novel imaging methods are developed and used to elucidate the crucial links between transport barriers and spatial heterogeneity in liposome accumulation. Finally, methods are presented to integrate quantitative imaging and mathematical modelling such that an accurate prediction of liposome transport in solid tumours is possible. In summary, this thesis presents and validates an image-guided mathematical

  8. Delivery of aerosolized drugs encapsulated in liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Yung-Sung; Lyons, C.R. [Univ. of New Mexico, Albuquerque, NM (United States); Schmid, M.H.

    1995-12-01

    Mycobacterium tuberculosis (Mtb) is an infectious disease that resides in the human lung. Due to the difficulty in completely killing off the disease in infected individuals, Mtb has developed drug-resistant forms and is on the rise in the human population. Therefore, ITRI and the University of New Mexico are collaborating to explore the treatment of Mtb by an aerosolized drug delivered directly to the lungs. In conclusion, it is feasible to obtain an appropriate size and concentration of the liposomes before and after aerosolization.

  9. RGD-modified pH-sensitive liposomes for docetaxel tumor targeting.

    Science.gov (United States)

    Chang, Minglu; Lu, Shanshan; Zhang, Fang; Zuo, Tiantian; Guan, Yuanyuan; Wei, Ting; Shao, Wei; Lin, Guimei

    2015-05-01

    Phosphatidylethanolamine-based pH-sensitive liposomes of various compositions have been described as efficient systems for delivery of therapeutic molecules into tumor cells. The aim of this work was to develop a drug delivery system based on pH-sensitive liposomes (PLPs) that were modified with arginine-glycine-aspartic acid (RGD) peptide to enhance the effectiveness of docetaxel treatment. Docetaxel/coumarin-6 loaded PLPs were prepared by the thin-film dispersion method and characterized in detail, including by particle size, polydispersity, zeta potential and drug encapsulation efficiency. In vitro studies using MCF-7, HepG2and A549 cells were employed to investigate cytotoxicity and cellular uptake of the drug solution or docetaxel/coumarin-6 loaded PLPs. The accumulation of 7-nitro-2-1,3-benzoxadiazol-4-yl (NBD)-labeled liposomes in vivo was studied through tumor section imaging of xenograft mouse models of MCF-7 24h after intravenous administration. The particle size of the non-coated or RGD modified PLPs ranged between 146 and 129nm. Drug release in vitro was modestly prolonged and had good pH sensitivity. In the in vitro study, RGD-coated PLPs showed higher cytotoxicity and cellular uptake relative to non-coated ones. The results of the in vivo study showed that RGD-coated PLPs had higher fluorescence, which suggested a more efficient accumulation than normal PLPs in tumors. In conclusion, these results confirmed RGD-modified PLPs as a potential drug delivery system to achieve controlled release and tumor targeting. PMID:25851582

  10. Pulsed ultrasound enhances the delivery of nitric oxide from bubble liposomes to ex vivo porcine carotid tissue

    Directory of Open Access Journals (Sweden)

    Sutton JT

    2014-10-01

    Full Text Available JT Sutton,1 JL Raymond,1 MC Verleye,2 GJ Pyne-Geithman,3 CK Holland4 1University of Cincinnati, Biomedical Engineering Program, Cincinnati, OH, 2University of Notre Dame Department of Chemical Engineering, Notre Dame, IN, 3University of Cincinnati, College of Medicine, Department of Neurosurgery and the University of Cincinnati Neuroscience Institute, and Mayfield Clinic, Cincinnati, OH, 4University of Cincinnati, College of Medicine, Internal Medicine, Division of Cardiovascular Diseases, Cincinnati, OH, USA Abstract: Ultrasound-mediated drug delivery is a novel technique for enhancing the penetration of drugs into diseased tissue beds noninvasively. By encapsulating drugs into microsized and nanosized liposomes, the therapeutic can be shielded from degradation within the vasculature until delivery to a target site by ultrasound exposure. Traditional in vitro or ex vivo techniques to quantify this delivery profile include optical approaches, cell culture, and electrophysiology. Here, we demonstrate an approach to characterize the degree of nitric oxide (NO delivery to porcine carotid tissue by direct measurement of ex vivo vascular tone. An ex vivo perfusion model was adapted to assess ultrasound-mediated delivery of NO. This potent vasodilator was coencapsulated with inert octafluoropropane gas to produce acoustically active bubble liposomes. Porcine carotid arteries were excised post mortem and mounted in a physiologic buffer solution. Vascular tone was assessed in real time by coupling the artery to an isometric force transducer. NO-loaded bubble liposomes were infused into the lumen of the artery, which was exposed to 1 MHz pulsed ultrasound at a peak-to-peak acoustic pressure amplitude of 0.34 MPa. Acoustic cavitation emissions were monitored passively. Changes in vascular tone were measured and compared with control and sham NO bubble liposome exposures. Our results demonstrate that ultrasound-triggered NO release from bubble liposomes

  11. Spectroscopic studies of alpha tocopherol interaction with a model liposome and its influence on oxidation dynamics

    Science.gov (United States)

    Krilov, Dubravka; Kosović, Marin; Serec, Kristina

    2014-08-01

    The influence of α-tocopherol on the surface conformation of liposome, as a model component of lipoproteins, and its role in oxidation process were studied. FT-IR spectra from suspensions of neat liposome, mixtures of liposome and α-tocopherol and liposome with incorporated α-tocopherol were analyzed. When α-tocopherol was incorporated into liposome, intensities of some bands were decreased or increased in comparison with the spectra of liposome and α-tocopherol mixture. These changes reflect the different localization of α-tocopherol in two types of liposome suspensions. The oxidation of liposome suspensions was initiated by addition of cupric ions. After prolonged oxidation, the differences in FT-IR spectra of oxidized samples were recorded. Differences were observed in comparison with spectra of native and oxidized liposomes were analyzed. The rate of oxidation was measured by EPR oximetry. Oxidation was generally very slow, but faster in liposome without α-tocopherol, indicating the protective role of α-tocopherol against liposome oxidation. On the other hand, liposome suspensions with EDTA in the buffer were not oxidized at all, while those with α-tocopherol and liposome mixture were only slightly oxidized. In this case the consumption of oxygen was the result of liposome oxidation supported by α-tocopherol. These results reflect the ambivalent role of α-tocopherol in liposome oxidation, similarly to findings in studies of lipoprotein oxidation.

  12. Liposomal cytarabine for leukemic and lymphomatous meningitis: recent developments.

    Science.gov (United States)

    Benesch, Martin; Urban, Christian

    2008-02-01

    Liposomal cytarabine (Depocyte) is a sustained-release formulation of cytarabine developed for intrathecal administration, ensuring prolonged cytotoxic drug concentrations of cytarabine in cerebrospinal fluid. Although liposomal cytarabine is increasingly used for the treatment (and prophylaxis) of CNS involvement in patients with leukemia/lymphoma, many of the recently presented clinical trials on liposomal cytarabine were retrospective in nature or used this drug on a compassionate basis. So far, one randomized Phase III study has shown significantly better response rates in patients with lymphomatous meningitis who received liposomal cytarabine compared with free cytarabine. Considerable concerns about the safety of this drug arose from recent observations that liposomal cytarabine might contribute to neurologic side effects when given too closely to high-dose systemic chemotherapy known to penetrate the brain-blood barrier. Superior efficacy of liposomal cytarabine compared with standard intrathecal therapy should be confirmed in prospective clinical trials. Careful adherence with preventive measures might help physicians to minimize side effects possibly related to the administration of liposomal cytarabine. PMID:18201152

  13. ELASTIC LIPOSOME: DRUG DELIVERY ACROSS HUMAN SKIN

    Directory of Open Access Journals (Sweden)

    Vardhan Harsh

    2012-04-01

    Full Text Available Transdermal drug delivery is hardly an old technology, since 1800’s and the technology is no longer just adhesive patches. Due to recent advances in technology and the ability to apply the drug to the site of action without rupturing the skin membrane, transdermal route is becoming a widely accepted route of drug administration. Recently, various strategies have been used to augment the transdermal delivery of bioactives. Mainly, they include iontophoresis, electrophoresis, sonophoresis, chemical permeation enhancers, micro needles, and vesicular system. Among these strategies elastic liposomes appear promising. Elastic liposomes possess an infrastructure consisting of hydrophobic and hydrophilic moieties together and as a result can accommodate drug molecules with wide range of solubility. It is an ultra deformable vesicle, elastic in nature which can squeeze itself through a pore which is many times smaller than its size owing to its elasticity. They can deform and pass through narrow constriction (from 5 to 10 times less than their own diameter without measurable loss. This high deformability gives better penetration of intact vesicles. This system is much more efficient at delivering a low and high molecular weight drug to the skin in terms of quantity and depth. The article speaks specifically on various phenomenon associated with the properties of these vesicles and their transport mechanisms. It also throws light on the effectiveness of conventional and deformable vesicles as drug delivery systems as well as their possible mode of action as transdermal drug carriers.

  14. Preparation and Characterization of Danofloxacin Mmesylate Liposomes

    Institute of Scientific and Technical Information of China (English)

    ZHANG Dexian; LI Jichang

    2011-01-01

    Five different methods were tested and compared to prepare danofloxacin mesylate liposomes, the ammonium sulfate gradient method with freeze-thawing steps was validated as the best one; the optimal preparation condition confirmed by orthogonal experiment was as follows: EPC-CH ratio was 3 : 2 and 2.6% SA was added to gain the positive electricity; drug-lipoid was 2 : 5, the concentration of ammonium sulfate was 250 mmol·L-1, water-oil ratio was 1:5, and they were incubated at 35℃ for 15 min. The prepared liposome products were ivory white semitransparent suspension, the electron microscope appearance was intact and globular or globular-like vesicles with uniformed distribution; the particle size was centralized from 3 to 7 gm, zeta-electric potential valued+ (15.92+1.49) mV, pH valued 6.02~0.09; HPLC method was established in quantitative analyses of danofloxacin and reverse dialysis with RP-HPLC method was validated for determination of entrapment efficiency. The entrapment efficiency results were all above 90%. They were stored at 4℃ with satisfied stability. Six months later, the appearance, characters and entrapment efficiency were almost with no change

  15. Dendrisomes: vesicular structures derived from a cationic lipidic dendron.

    Science.gov (United States)

    Al-Jamal, Khuloud T; Sakthivel, Thiagarajan; Florence, Alexander T

    2005-01-01

    The behavior of a novel synthetic lipidic cationic lysine-based dendron (partial dendrimer) in aqueous media and its ability, with and without cholesterol, to self-assemble into higher order structures was studied to gain an understanding of these structures as potential drug carriers. The dendron was prepared by solid-phase peptide synthesis. A reverse-phase evaporation (REV) technique was used to prepare cationic vesicular aggregates of the dendron with different molar ratios of cholesterol. The size and zeta potential of these supramolecular aggregates or "dendrisomes" was determined by photon correlation spectroscopy (PCS). Dendrisome morphology and thermotropic properties were studied by transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). Radiolabeled penicillin G was used as a model of a negatively charged water-soluble compound to investigate the encapsulation efficiency of the dendrisomes. In vitro release of the drug was determined using as a comparator a REV liposome formulation. Dendrisomes of all compositions have higher encapsulation efficiencies and slower release rates compared to the comparator. Cholesterol was found both to increase the size of the aggregates from around 310 to 560 nm and to increase shape irregularities, but did not change the positive zeta potential, in the order of +50 mV, of the dendrisomes. Cholesterol decreases penicillin G entrapment efficiency but increases solute leakage at 25 degrees C. PMID:15761934

  16. Application of liposomes in medicine and drug delivery.

    Science.gov (United States)

    Daraee, Hadis; Etemadi, Ali; Kouhi, Mohammad; Alimirzalu, Samira; Akbarzadeh, Abolfazl

    2016-01-01

    Liposomes provide an established basis for the sustainable development of different commercial products for treatment of medical diseases by the smart delivery of drugs. The industrial applications include the use of liposomes as drug delivery vehicles in medicine, adjuvants in vaccination, signal enhancers/carriers in medical diagnostics and analytical biochemistry, solubilizers for various ingredients as well as support matrices for various ingredients and penetration enhancers in cosmetics. In this review, we summarize the main applications and liposome-based commercial products that are currently used in the medical field. PMID:25222036

  17. Studies on precellular evolution - The encapsulation of polyribonucleotides by liposomes

    Science.gov (United States)

    Baeza, I.; Ibanez, M.; Santiago, J. C.; Wong, C.; Lazcano, A.

    1986-01-01

    Liposomes have been suggested as possible models of precellular systems formed in the early Archean earth from lipids of nonenzymatic origin. Since it is generally accepted that RNA molecules preceded double-stranded DNA molecules as genetic material, the encapsulation of polyribonucleotides within liposomes (made from dipalmitoyl phosphatidylcholine and from egg yolk phosphatidylcholine) was studied. Quantitative determinations show that approximately 50 percent of the available lipids form liposomes, and that up to 5 percent of the polyribonucleotides can be entrapped by them. Also studied was the encapsulation of polyribonucleotides in the presence of urea and cyanamide and of Zn(2+) and Pb(2+).

  18. 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...

  19. Liposomal Drug Products: A Quality by Design Approach

    Science.gov (United States)

    Xu, Xiaoming

    Quality by Design (QbD) principles has been applied to the development of two liposomal formulations, containing a hydrophilic small molecule therapeutic (Tenofovir) and a protein therapeutic (superoxide dismutase). The goal of the research is to provide critical information on 1) how to reduce the preparation variability in liposome formulations, and 2) how to increase drug encapsulation inside liposomes to reduce manufacturing cost. Most notably, an improved liposome preparation method was developed which increased the encapsulation efficiency of hydrophilic molecules. In particular, this method allows for very high encapsulation efficiency. For example, encapsulation efficiencies of up to 50% have been achieved, whereas previously only 20% or less have been reported. Another significant outcome from this research is a first principle mathematical model to predict the encapsulation efficiency of hydrophilic drugs in unilamellar liposomes. This mathematical model will be useful in: formulation development to rapidly achieve optimized formulations; comparison of drug encapsulation efficiencies of liposomes prepared using different methods; and assisting in the development of suitable process analytical technologies to achieve real-time monitoring and control of drug encapsulation during manufacturing. A novel two-stage reverse dialysis in vitro release testing method has also been developed for passively targeted liposomes, which uses the first stage to mimic the circulation of liposomes in the body and the second stage to imitate the drug release process at the target. The developed in vitro release testing method can be used to distinguish formulations with varied compositions for quality control testing purposes. This developed method may pave the way to the development of more biorelevant quality control testing methods for liposomal drug products in the future. The QbD case studies performed in this research are examples of how this approach can be used to

  20. A novel cationic lipid with intrinsic antitumor activity to facilitate gene therapy of TRAIL DNA.

    Science.gov (United States)

    Luo, Cong; Miao, Lei; Zhao, Yi; Musetti, Sara; Wang, Yuhua; Shi, Kai; Huang, Leaf

    2016-09-01

    Metformin (dimethylbiguanide) has been found to be effective for the treatment of a wide range of cancer. Herein, a novel lipid (1,2-di-(9Z-octadecenoyl)-3-biguanide-propane (DOBP)) was elaborately designed by utilizing biguanide as the cationic head group. This novel cationic lipid was intended to act as a gene carrier with intrinsic antitumor activity. When compared with 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (DOTAP), a commercially available cationic lipid with a similar structure, the blank liposomes consisting of DOBP showed much more potent antitumor effects than DOTAP in human lung tumor xenografts, following an antitumor mechanism similar to metformin. Given its cationic head group, biguanide, DOBP could encapsulate TNF-related apoptosis-inducing ligand (TRAIL) plasmids into Lipid-Protamine-DNA (LPD) nanoparticles (NPs) for systemic gene delivery. DOBP-LPD-TRAIL NPs demonstrated distinct superiority in delaying tumor progression over DOTAP-LPD-TRAIL NPs, due to the intrinsic antitumor activity combined with TRAIL-induced apoptosis in the tumor. These results indicate that DOBP could be used as a versatile and promising cationic lipid for improving the therapeutic index of gene therapy in cancer treatment. PMID:27344367

  1. Temperature-dependent bifurcation of cooperative interactions in pure and enriched in β-carotene DPPC liposomes.

    Science.gov (United States)

    Augustyńska, D; Burda, K; Jemioła-Rzemińska, M; Strzałka, K

    2016-08-25

    We examined the influence of temperature on lipid intermolecular interactions and the organization of bilayers within multilamellar dipalmitoylphosphatidylcholine (DPPC) liposomes. We also investigated the effect of 0.5 mol% β-carotene, a non-polar carotenoid, on the adhesive properties of these liposomes. Atomic force microscopy (AFM) and differential scanning calorimetry (DSC) were used to correlate the changes in the physical properties of the liposomal systems with their thermotropic behaviour. Using DSC we detected two transitions in pure DPPC vesicles and in those containing 0.5 mol% β-carotene. In both systems the pretransition occurred at 34.5(1)°C and the main phase transition at 41.4 °C during heating. Upon cooling, the temperatures of the pretransition and the main transition decreased by about 6 °C and 1 °C, respectively. Changes in enthalpy and entropy were also similar in the two investigated systems. Data obtained in parallel AFM force experiments show that the adhesive forces between the liposomal systems and AFM probe strongly depend on the loading rate. Moreover, their characteristic monotonic changes and discontinuities are sensitive to temperature. In the range of temperatures from 27 °C to 31 °C, i.e. below the temperature of phase transition from gel to ripple phase, the adhesive forces measured in a water environment are about an order of magnitude higher in the presence of β-carotene than in pure DPPC liposomes. The observed variable dependence of adhesion on the loading rate suggests that there are changes in the long- and short-range interactions between lipids, and that these may be related to the occurrence of some clustering effects. In addition, the simultaneous existence of different subphases was found in the gel phase of DPPC liposomes. The presence of β-carotene at a level of 0.5 mol% stimulates the structural reorganization of DPPC multilamellar vesicles and enhances the bifurcation phenomenon detected in these

  2. Modulation of pyridinium cationic lipid-DNA complex properties by pyridinium gemini surfactants and its impact on lipoplex transfection properties.

    Science.gov (United States)

    Sharma, Vishnu Dutt; Lees, Julia; Hoffman, Nicholas E; Brailoiu, Eugen; Madesh, Muniswamy; Wunder, Stephanie L; Ilies, Marc A

    2014-02-01

    The study presents the effects of blending a cationic gemini surfactant into cationic lipid bilayers and its impact on the plasmid DNA compaction and delivery process. Using nanoDSC, dynamic light scattering, zeta potential, and electrophoretic mobility measurements, together with transfection (2D- and 3D-) and viability assays, we identified the main physicochemical parameters of the lipid bilayers, liposomes, and lipoplexes that are affected by the gemini surfactant addition. We also correlated the cationic bilayer composition with the dynamics of the DNA compaction process and with transfection efficiency, cytotoxicity, and the internalization mechanism of the resultant nucleic acid complexes. We found that the blending of gemini surfactant into the cationic bilayers fluidized the supramolecular assemblies, reduced the amount of positive charge required to fully compact the plasmid DNA and, in certain cases, changed the internalization mechanism of the lipoplexes. The transfection efficiency of select ternary lipoplexes derived from cationic gemini surfactants and lipids was several times superior to the transfection efficiency of corresponding binary lipoplexes, also surpassing standard transfection systems. The overall impact of gemini surfactants into the formation and dynamic of cationic bilayers was found to depend heavily on the presence of colipids, their nature, and amount present in lipoplexes. The study confirmed the possibility of combining the specific properties of pyridinium gemini surfactants and cationic lipids synergistically to obtain efficient synthetic transfection systems with negligible cytotoxicity useful for therapeutic gene delivery. PMID:24377350

  3. Effect of liposomal fluidity on skin permeation of sodium fluorescein entrapped in liposomes

    OpenAIRE

    Subongkot T; Ngawhirunpat T

    2015-01-01

    Thirapit Subongkot,1 Tanasait Ngawhirunpat21Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, Thailand; 2Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, ThailandAbstract: The purpose of this study was to investigate the effect of ultradeformable liposome components, Tween 20 and terpenes, on vesicle fluidity. The fluidity was evaluated by electron spin resonance spectroscopy using 5-dox...

  4. In Vitro Evaluation of the Efficacy of Liposomal and Pegylated Liposomal Hydroxyurea

    OpenAIRE

    Alavi, Seyed Ebrahim; Esfahani, Maedeh Koohi Moftakhari; Ghassemi, Soheil; Akbarzadeh, Azim; Hassanshahi, Gholamhossein

    2013-01-01

    Breast cancer is one of the most frequent cancer types within women population. Hydroxyurea (HU) is a chemotherapy compound for treatment of patients with cancer diagnosis, including breast cancer associated with several adverse effects. In this study, we applied nanotechnology to decreased drug side effects along with improvement of therapeutic index. Liposomation is widely used in modern pharmacological developments in order to enhance the effects of the drugs. To achieve this, in this stud...

  5. The Flocculating Cationic Polypetide from Moringa oleifera Seeds Damages Bacterial Cell Membranes by Causing Membrane Fusion.

    Science.gov (United States)

    Shebek, Kevin; Schantz, Allen B; Sines, Ian; Lauser, Kathleen; Velegol, Stephanie; Kumar, Manish

    2015-04-21

    A cationic protein isolated from the seeds of the Moringa oleifera tree has been extensively studied for use in water treatment in developing countries and has been proposed for use in antimicrobial and therapeutic applications. However, the molecular basis for the antimicrobial action of this peptide, Moringa oleifera cationic protein (MOCP), has not been previously elucidated. We demonstrate here that a dominant mechanism of MOCP antimicrobial activity is membrane fusion. We used a combination of cryogenic electron microscopy (cryo-EM) and fluorescence assays to observe and study the kinetics of fusion of membranes in liposomes representing model microbial cells. We also conducted cryo-EM experiments on E. coli cells where MOCP was seen to fuse the inner and outer membranes. Coarse-grained molecular dynamics simulations of membrane vesicles with MOCP molecules were used to elucidate steps in peptide adsorption, stalk formation, and fusion between membranes. PMID:25845029

  6. 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

    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......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...... 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...

  7. Sustained distribution of aerosolized PEGylated liposomes in epithelial lining fluids on alveolar surfaces.

    Science.gov (United States)

    Kaneko, Keita; Togami, Kohei; Yamamoto, Eri; Wang, Shujun; Morimoto, Kazuhiro; Itagaki, Shirou; Chono, Sumio

    2016-10-01

    The distribution characteristics of aerosolized PEGylated liposomes in alveolar epithelial lining fluid (ELF) were examined in rats, and the ensuing mechanisms were investigated in the in vitro uptake and protein adsorption experiments. Nonmodified or PEGylated liposomes (particle size 100 nm) were aerosolized into rat lungs. PEGylated liposomes were distributed more sustainably in ELFs than nonmodified liposomes. Furthermore, the uptake of PEGylated liposomes by alveolar macrophages (AMs) was less than that of nonmodified liposomes. In further in vitro uptake experiments, nonmodified and PEGylated liposomes were opsonized with rat ELF components and then added to NR8383 cells as cultured rat AMs. The uptake of opsonized PEGylated liposomes by NR8383 cells was lower than that of opsonized nonmodified liposomes. Moreover, the protein absorption levels in opsonized PEGylated liposomes were lower than those in opsonized nonmodified liposomes. These findings suggest that sustained distributions of aerosolized PEGylated liposomes in ELFs reflect evasion of liposomal opsonization with surfactant proteins and consequent reductions in uptake by AMs. These data indicate the potential of PEGylated liposomes as aerosol-based drug delivery system that target ELF for the treatment of respiratory diseases. PMID:27334278

  8. Targeting and stimulation of the zebrafish (Danio rerio) innate immune system with LPS/dsRNA-loaded nanoliposomes

    OpenAIRE

    Ruyra Ripoll, Àngels; Cano Sarabia, Mary; García-Valtanen, Pablo; Yero Corona, Daniel; Gibert, Isidre; Simon A MacKenzie; Estepa, Amparo; Maspoch Comamala, Daniel; Roher Armentia, Nerea

    2014-01-01

    Herein we report the use of immunostimulant-loaded nanoliposomes (called NLcliposomes) as a strategy to protect fish against bacterial and/or viral infections. This work entailed developing a method for in vivo tracking of the liposomes administered to adult zebrafish that enables evaluation of their in vivo dynamics and characterisation of their tissue distribution. The NLc liposomes, which co-encapsulate poly(I:C) and LPS, accumulate in immune tissues and in immunologically relevant cells s...

  9. Atmospheric-pressure guided streamers for liposomal membrane disruption

    Science.gov (United States)

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

    2012-12-01

    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.

  10. Atmospheric-pressure guided streamers for liposomal membrane disruption

    International Nuclear Information System (INIS)

    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.

  11. Avoiding failed reconstitution of ultradeformable liposomes upon dehydration.

    Science.gov (United States)

    Montanari, J; Roncaglia, D I; Lado, L A; Morilla, M J; Romero, E L

    2009-05-01

    Although freeze-drying is an ordinarily used technique to dehydrate conventional liposomes, we have found that ultradeformable liposomes (UDLs) suffered irreversible aggregation when rehydrated upon freeze-drying (99.4% water elimination), even in high sugar content (4/1 sucrose/lipid mass ratio). When dehydrated by speed vac and vacuum drying, two alternative techniques that rendered less pronounced dehydration (94.27 and 96.2% water elimination, respectively) and avoid ice formation, however, UDL could only be successfully rehydrated when vacuum dried in 4/1 sucrose/lipid mass ratios. Conventional liposomes, on the other hand, were successfully reconstituted upon dehydrated by the three methods in lower sugar content (2/1 sucrose/lipid mass ratio). These results indicated that the 27% mole sodium cholate within the UDL lipid matrix was responsible for a greater and differential mechanical sensitivity of the bilayers to the different dehydration stress, as compared to conventional liposomes. PMID:19429279

  12. Atmospheric-pressure guided streamers for liposomal membrane disruption

    Energy Technology Data Exchange (ETDEWEB)

    Svarnas, P.; Aleiferis, Sp. [High Voltage Laboratory, Department of Electrical and Computer Engineering, University of Patras, Rion 26504 (Greece); Matrali, S. H. [Pharmaceutical Technology Laboratory, Department of Pharmacy, University of Patras, Rion 26504 (Greece); Gazeli, K. [High Voltage Laboratory, Department of Electrical and Computer Engineering, University of Patras, Rion 26504 (Greece); IPREM-LCABIE, Plasmas et Applications, UPPA, 64000 Pau (France); Clement, F. [IPREM-LCABIE, Plasmas et Applications, UPPA, 64000 Pau (France); Antimisiaris, S. G. [Pharmaceutical Technology Laboratory, Department of Pharmacy, University of Patras, Rion 26504 (Greece); Institute of Chemical Engineering Sciences (ICES)-FORTH, Rion 26504 (Greece)

    2012-12-24

    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.

  13. 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.

  14. Analysis of liposomes using asymmetrical flow field-flow fractionation

    DEFF Research Database (Denmark)

    Kuntsche, Judith; Decker, Christiane; Fahr, Alfred

    2012-01-01

    Liposomes composed of dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylglycerol were analyzed by asymmetrical flow field-flow fractionation coupled with multi-angle laser light scattering. In addition to evaluation of fractionation conditions (flow conditions, sample mass, carrier liquid...

  15. Effect of liposomal amphotericin B on murine macrophages and lymphocytes.

    OpenAIRE

    Mehta, R T; Mehta, K; Lopez-Berestein, G; Juliano, R. L.

    1985-01-01

    The effect of liposome-encapsulated amphotericin B on mouse macrophages and on T- and B-lymphocyte functions in vitro was compared with that of free amphotericin B. Liposomal amphotericin B was generally less toxic than the free form of the drug. Low concentrations of free amphotericin B completely inhibited the serum-dependent induction of transglutaminase, a marker for macrophage differentiation, and production of superoxide anion by macrophages, whereas encapsulation of the drug within lip...

  16. Gadolinium-containing phosphatidylserine liposomes for molecular imaging of atherosclerosis

    OpenAIRE

    Maiseyeu, Andrei; Mihai, Georgeta; Kampfrath, Thomas; Simonetti, Orlando P.; Sen, Chandan K.; Roy, Sashwati; Rajagopalan, Sanjay; Parthasarathy, Sampath

    2009-01-01

    Exteriorized phosphatidylserine (PS) residues in apoptotic cells trigger rapid phagocytosis by macrophage scavenger receptor pathways. Mimicking apoptosis with liposomes containing PS may represent an attractive approach for molecular imaging of atherosclerosis. We investigated the utility of paramagnetic gadolinium liposomes enriched with PS (Gd-PS) in imaging atherosclerotic plaque. Gd-PS-containing Gd-conjugated lipids, fluorescent rhodamine, and PS were prepared and characterized. Cellula...

  17. Engineering hybrid exosomes by membrane fusion with liposomes

    OpenAIRE

    Sato, Yuko T.; Kaori Umezaki; Shinichi Sawada; Sada-atsu Mukai; Yoshihiro Sasaki; Naozumi Harada; Hiroshi Shiku; Kazunari Akiyoshi

    2016-01-01

    Exosomes are a valuable biomaterial for the development of novel nanocarriers as functionally advanced drug delivery systems. To control and modify the performance of exosomal nanocarriers, we developed hybrid exosomes by fusing their membranes with liposomes using the freeze–thaw method. Exosomes embedded with a specific membrane protein isolated from genetically modified cells were fused with various liposomes, confirming that membrane engineering methods can be combined with genetic modifi...

  18. Labelling of liposomes with intercalating perylene fluorescent dyes

    OpenAIRE

    Schott, H; Cunow, D. von; Langhals, Heinz

    1992-01-01

    The high fluorescent potential and the exceptional photostability of lipophilic derivatives of perylene-3,4:9,10-bis(dicarboximides) are utilized for the fluorescence-labelling of liposomes. The preparation of the liposomes is affected by supersonic starting from a lipid mixture consisting of the matrix lipids soy lecithin, cholesterol, -tocopherol and the perylene dyes. From a multitude of perylene derivatives investigated only those are optimally incorporated inot the bilayer membrane of un...

  19. Influence of osmotic stress on liposome size and morphology

    OpenAIRE

    Moen, Helene

    2008-01-01

    Liposomes are currently being investigated as potential parenterally used drug carriers. The main factor that influences the in vivo behavior of such liposomes is their vesicle size. A detailed and reliable knowledge of vesicle size is therefore necessary in order to interpret results of physical and biological investigations in a correct manner. It has earlier been discovered that it is feasible to determine the size distribution of vesicle dispersions in a reliable manner and it appears...

  20. Liposome-coated quantum dots targeting the sentinel lymph node

    Energy Technology Data Exchange (ETDEWEB)

    Chu Maoquan, E-mail: mqchu98@tongji.edu.cn; Zhuo Shu; Xu Jiang; Sheng Qiunan; Hou Shengke; Wang Ruifei [Tongji University, School of Life Science and Technology (China)

    2010-01-15

    Sentinel lymph node (SLN) mapping with near-infrared (NIR) quantum dot (QDs) have many advantages over traditional methods. However, as an inorganic nanomaterial, QDs have low biocompatibility and low affinity to the lymphatic system. Here, we encapsulated QDs into nanoscale liposomes and then used these liposome-coated QDs for SLN mapping. The results showed that the liposome-coated QDs exhibited core-shell characterization, and their fluorescence emission did not decrease but slightly increased after being continuously excited by a xenon lamp source (150 W) at 488 nm at 37 {sup o}C for 1 h. After storing at 4 {sup o}C for more than one and half years, the liposome-coated QDs were found to have retained their spherical structure containing a large amount of QDs. When liposome-coated QDs with average size of 55.43 nm were injected intradermally into the paw of a mouse, the SLN was strongly fluorescent within only a few seconds and visualized easily in real time. Moreover, the fluorescence of the QDs trapped in the SLN could be observed for at least 24 h. Compared with the SLN mapping of QDs absent of liposomes and liposome-coated QDs with a larger average size (100.3 and 153.6 nm), more QDs migrated into the SLN when the liposome-coated QDs with smaller average size (55.43 nm) were injected. This technique may make a great contribution to the improvement of the biocompatibility of QDs and the targeting delivery capacity of QDs into the SLN.

  1. Technology of Liposomal Tiosens, Cifelin and Lysomustin for Industrial Purposes

    Science.gov (United States)

    Sanarova, E. V.; Kotova, E. A.; Lantsova, A. V.

    2012-02-01

    This work is devoted to the development of national antineoplastic drug (Tiosens, Cifelin, Lysomustin) liposomal dosage form (LDF) circuit technology and their manufacturing technology. In modern oncology liposomes, which are hollow phospholipid vesicles, are used as delivery systems protected drugs from biodegradation, and healthy cells from the toxic effect of chemotherapeutic agents. The technology of their production is stretching and multistage. It is also necessary to give consideration a lot of factors that influence on the finished product quality.

  2. Liposome-coated quantum dots targeting the sentinel lymph node

    International Nuclear Information System (INIS)

    Sentinel lymph node (SLN) mapping with near-infrared (NIR) quantum dot (QDs) have many advantages over traditional methods. However, as an inorganic nanomaterial, QDs have low biocompatibility and low affinity to the lymphatic system. Here, we encapsulated QDs into nanoscale liposomes and then used these liposome-coated QDs for SLN mapping. The results showed that the liposome-coated QDs exhibited core-shell characterization, and their fluorescence emission did not decrease but slightly increased after being continuously excited by a xenon lamp source (150 W) at 488 nm at 37 oC for 1 h. After storing at 4 oC for more than one and half years, the liposome-coated QDs were found to have retained their spherical structure containing a large amount of QDs. When liposome-coated QDs with average size of 55.43 nm were injected intradermally into the paw of a mouse, the SLN was strongly fluorescent within only a few seconds and visualized easily in real time. Moreover, the fluorescence of the QDs trapped in the SLN could be observed for at least 24 h. Compared with the SLN mapping of QDs absent of liposomes and liposome-coated QDs with a larger average size (100.3 and 153.6 nm), more QDs migrated into the SLN when the liposome-coated QDs with smaller average size (55.43 nm) were injected. This technique may make a great contribution to the improvement of the biocompatibility of QDs and the targeting delivery capacity of QDs into the SLN.

  3. DESIGN, DEVELOPMENT AND CHARACTERIZATION OF LIPOSOMAL NEEM GEL

    Directory of Open Access Journals (Sweden)

    ASMITA SINGH

    2014-04-01

    Full Text Available Purpose: Liposomal formulations have been successfully used in the treatment of a number of dermatological diseases. Various synthetic as well as herbal drugs are incorporated into liposome to improve its efficacy. Incorporation of herbal extract into liposome reduces side effects which are associated with the synthetic ones. Azadirachta indica leaves possesse good anti bacterial activity, confirming the great potential of bioactive compounds of neem. Among aqueous extract and alcoholic extract, alcoholic leaf extracts of A. indica were found to be more active towards the bacterial species. Hence, this extract was incorporated into liposomes to enhance its activity in skin delivery. The objective of the present research work is to convert this age old miraculous herb into nanotechnology based formulations i.e. liposomes. An attempt has been made to prepare liposomal Neem gel for topical use for anti-microbial activity. Methods: Methanolic Neem Extract (MeNE was incorporated into liposomes by thin film hydration method. The batch having lipid ratio i.e. Soya lecithin: Cholesterol (4:1; MeNE concentration 80 mg with entrapment efficiency 69.52 ±1.9% was finalized. Results and Conclusions: The vesicle size was found to be 3.2μm ± 0.67. In vitro drug diffusion and skin retention from liposomal gel was found to be 62.178% ± 0.91 and 20.03% ± 0.63 respectively. Stability studies indicated that formulation was stable over a period of 3 months when stored at 2-8°C.

  4. Advanced strategies in liposomal cancer therapy

    DEFF Research Database (Denmark)

    Andresen, Thomas Lars; Jensen, Simon Skøde; Jørgensen, Kent

    2005-01-01

    Tumor specific drug delivery has become increasingly interesting in cancer therapy, as the use of chemotherapeutics is often limited due to severe side effects. Conventional drug delivery systems have shown low efficiency and a continuous search for more advanced drug delivery principles is...... therefore of great importance. In the first part of this review, we present current strategies in the drug delivery field, focusing on site-specific triggered drug release from liposomes in cancerous tissue. Currently marketed drug delivery systems lack the ability to actively release the carried drug and......, none of them have yet led to marketed drugs and are still far from achieving this goal. The most advanced and prospective technologies are probably the prodrug strategies where nontoxic drugs are carried and activated specifically in the malignant tissue by overexpressed enzymes. In the second part of...

  5. Ultrasonic Activation of Thermally Sensitive Liposomes

    Science.gov (United States)

    Mylonopouloua, Eleonora; Arvanitisa, Costas D.; Bazan-Peregrinoa, Miriam; Arora, Manish; Coussios, Constantin C.

    2010-03-01

    Cancerous cells are known to be more vulnerable to mild hyperthermia than healthy cells, which can survive temperatures above 43° C for brief periods of time. Currently in phase III clinical trials for liver cancer, ThermoDox® (Celsion Corporation) is a drug delivery system containing doxorubicin, a common anti-cancer agent, encapsulated within a thermally sensitive liposome designed to release its contents above 39.5° C. Activation of such an agent with the use of HIFU, which can generate localized heating non-invasively, would combine the benefits of targeted chemotherapy and hyperthermia while minimizing undesirable systemic side-effects. To that end, the resolution and reliability with which HIFU-induced hyperthermia can achieve Thermodox® release was investigated using a novel agar-based gel embedding liposomes at clinically relevant concentrations (0.02 mg/ml). The gel was exposed to 1.15 MHz HIFU (Sonic Concepts H102) using a range of clinically relevant pressure amplitudes (0-6 MPa peak rarefactional), duty cycles (10-100%) and exposure durations to identify optimal insonation conditions for complete doxorubicin release. The corresponding temperature profiles were mapped with 0.5 mm spatial resolution using an embedded needle thermocouple; drug release was quantified using fluorimetry. Complete release over the HIFU focal area was obtained for 6-s continuous wave exposure at 5.2 MPa peak rarefactional pressure, i.e. under exposure conditions for which the temperature exceeded 43° C throughout the focal volume. For a given HIFU energy input, both the final temperature reached and the rate of heating were found to affect release significantly. However, ThermoDox® release was achieved only due to thermal effects of HIFU, and not by other ultrasound effects, such as cavitation without heating, showing robustness of HIFU-induced hyperthermia as a release mechanism.

  6. Peptide Anchor for Folate-Targeted Liposomal Delivery.

    Science.gov (United States)

    Nogueira, Eugénia; Mangialavori, Irene C; Loureiro, Ana; Azoia, Nuno G; Sárria, Marisa P; Nogueira, Patrícia; Freitas, Jaime; Härmark, Johan; Shimanovich, Ulyana; Rollett, Alexandra; Lacroix, Ghislaine; Bernardes, Gonçalo J L; Guebitz, Georg; Hebert, Hans; Moreira, Alexandra; Carmo, Alexandre M; Rossi, Juan Pablo F C; Gomes, Andreia C; Preto, Ana; Cavaco-Paulo, Artur

    2015-09-14

    Specific folate receptors are abundantly overexpressed in chronically activated macrophages and in most cancer cells. Directed folate receptor targeting using liposomes is usually achieved using folate linked to a phospholipid or cholesterol anchor. This link is formed using a large spacer like polyethylene glycol. Here, we report an innovative strategy for targeted liposome delivery that uses a hydrophobic fragment of surfactant protein D linked to folate. Our proposed spacer is a small 4 amino acid residue linker. The peptide conjugate inserts deeply into the lipid bilayer without affecting liposomal integrity, with high stability and specificity. To compare the drug delivery potential of both liposomal targeting systems, we encapsulated the nuclear dye Hoechst 34580. The eventual increase in blue fluorescence would only be detectable upon liposome disruption, leading to specific binding of this dye to DNA. Our delivery system was proven to be more efficient (2-fold) in Caco-2 cells than classic systems where the folate moiety is linked to liposomes by polyethylene glycol. PMID:26241560

  7. 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. PMID:19552578

  8. Effectiveness of liposomal paclitaxel against MCF-7 breast cancer cells.

    Science.gov (United States)

    Heney, Melanie; Alipour, Misagh; Vergidis, Dimitrios; Omri, Abdelwahab; Mugabe, Clement; Th'ng, John; Suntres, Zacharias

    2010-12-01

    Paclitaxel is an effective chemotherapeutic agent that is widely used for the treatment of several cancers, including breast, ovarian, and non-small-cell lung cancer. Due to its high lipophilicity, paclitaxel is difficult to administer and requires solubilization with Cremophor EL (polyethoxylated castor oil) and ethanol, which often lead to adverse side effects, including life-threatening anaphylaxis. Incorporation of paclitaxel in dimyristoylphosphatidylcholine:dimyristoylphosphatidylglycerol (DPPC:DMPG) liposomes can facilitate its delivery to cancer cells and eliminate the adverse reactions associated with the Cremophor EL vehicle. Accordingly, the effectiveness of liposomal paclitaxel on MCF-7 breast cancer cells was examined. The results from this study showed that (i) the lipid components of the liposomal formulation were nontoxic, (ii) the cytotoxic effects of liposomal paclitaxel were improved when compared with those seen with conventional paclitaxel, and (iii) the intracellular paclitaxel levels were higher in MCF-7 cells treated with the liposomal paclitaxel formulation. The results of these studies showed that delivery of paclitaxel as a liposomal formulation could be a promising strategy for enhancing its chemotherapeutic effects. PMID:21164564

  9. 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.

  10. Gene Transfer by Guanidinium-Cholesterol Cationic Lipids into Airway Epithelial Cells in vitro and in vivo

    Science.gov (United States)

    Oudrhiri, Noufissa; Vigneron, Jean-Pierre; Peuchmaur, Michel; Leclerc, Tony; Lehn, Jean-Marie; Lehn, Pierre

    1997-03-01

    Synthetic vectors represent an attractive alternative approach to viral vectors for gene transfer, in particular into airway epithelial cells for lung-directed gene therapy for cystic fibrosis. Having recently found that guanidinium-cholesterol cationic lipids are efficient reagents for gene transfer into mammalian cell lines in vitro, we have investigated their use for gene delivery into primary airway epithelial cells in vitro and in vivo. The results obtained indicate that the lipid bis (guanidinium)-tren-cholesterol (BGTC) can be used to transfer a reporter gene into primary human airway epithelial cells in culture. Furthermore, liposomes composed of BGTC and dioleoyl phosphatidylethanolamine (DOPE) are efficient for gene delivery to the mouse airway epithelium in vivo. Transfected cells were detected both in the surface epithelium and in submucosal glands. In addition, the transfection efficiency of BGTC/DOPE liposomes in vivo was quantitatively assessed by using the luciferase reporter gene system.

  11. Nano-Drugs Based on Nano Sterically Stabilized Liposomes for the Treatment of Inflammatory Neurodegenerative Diseases.

    Science.gov (United States)

    Turjeman, Keren; Bavli, Yaelle; Kizelsztein, Pablo; Schilt, Yaelle; Allon, Nahum; Katzir, Tamar Blumenfeld; Sasson, Efrat; Raviv, Uri; Ovadia, Haim; Barenholz, Yechezkel

    2015-01-01

    The present study shows the advantages of liposome-based nano-drugs as a novel strategy of delivering active pharmaceutical ingredients for treatment of neurodegenerative diseases that involve neuroinflammation. We used the most common animal model for multiple sclerosis (MS), mice experimental autoimmune encephalomyelitis (EAE). The main challenges to overcome are the drugs' unfavorable pharmacokinetics and biodistribution, which result in inadequate therapeutic efficacy and in drug toxicity (due to high and repeated dosage). We designed two different liposomal nano-drugs, i.e., nano sterically stabilized liposomes (NSSL), remote loaded with: (a) a "water-soluble" amphipathic weak acid glucocorticosteroid prodrug, methylprednisolone hemisuccinate (MPS) or (b) the amphipathic weak base nitroxide, Tempamine (TMN). For the NSSL-MPS we also compared the effect of passive targeting alone and of active targeting based on short peptide fragments of ApoE or of β-amyloid. Our results clearly show that for NSSL-MPS, active targeting is not superior to passive targeting. For the NSSL-MPS and the NSSL-TMN it was demonstrated that these nano-drugs ameliorate the clinical signs and the pathology of EAE. We have further investigated the MPS nano-drug's therapeutic efficacy and its mechanism of action in both the acute and the adoptive transfer EAE models, as well as optimizing the perfomance of the TMN nano-drug. The highly efficacious anti-inflammatory therapeutic feature of these two nano-drugs meets the criteria of disease-modifying drugs and supports further development and evaluation of these nano-drugs as potential therapeutic agents for diseases with an inflammatory component. PMID:26147975

  12. Simultaneous optical measurement of osmotic and diffusional water permeability in cells and liposomes.

    Science.gov (United States)

    Ye, R G; Verkman, A S

    1989-01-24

    A quantitative description of transmembrane water transport requires specification of osmotic (Pf) and diffusional (Pd) water permeability coefficients. Methodology has been developed to measure Pf and Pd simultaneously on the basis of the sensitivity and rapid response of the fluorophore aminonaphthalenetrisulfonic acid (ANTS) to solution H2O/D2O content. Cells loaded with ANTS in an H2O buffer were subjected to an inward osmotic gradient with a D2O buffer in a stopped-flow apparatus. The time courses of cell volume (giving Pf) and H2O/D2O content (giving Pd) were recorded with dual photomultiplier detection of scattered light intensity and ANTS fluorescence, respectively. The method was validated by using sealed red cell ghosts and artificial liposomes reconstituted with the pore-forming agent gramicidin D. At 25 degrees C, red cell ghost Pf was 0.021 cm/s with Pd 0.005 cm/s (H2O/D2O exchange time 7.9 ms). Pf and Pd were inhibited by 90% and 45% upon addition of 0.5 mM HgCl2. The activation energy for Pd increased from 5.1 kcal/mol to 10 kcal/mol with addition of HgCl2 (18-35 degrees C). In 90% phosphatidylcholine (PC)/10% cholesterol liposomes prepared by bath sonication and exclusion chromatography, Pf and Pd were 5.1 X 10(-4) and 6.3 X 10(-4) cm/s, respectively (23 degrees C). Addition of gramicidin D (0.1 micrograms/mg of PC) resulted in a further increment in Pf and Pd of 7 X 10(-4) and 3 X 10(-4) cm/s, respectively. These results validate the new methodology and demonstrate its utility for rapid determination of Pf/Pd in biological membranes and in liposomes reconstituted with water channels. PMID:2540807

  13. Pharmacokinetics and pharmacodynamics evaluation of a thermosensitive chitosan based hydrogel containing liposomal doxorubicin.

    Science.gov (United States)

    Ren, Shuangxia; Dai, Yu; Li, Cuiyun; Qiu, Zhixia; Wang, Xin; Tian, Fengjie; Zhou, Sufeng; Liu, Qi; Xing, Han; Lu, Yang; Chen, Xijing; Li, Ning

    2016-09-20

    In situ gelling thermosensitive hydrogel formulation has been reported to effectively sustain the release of macromolecules for a long time. However, the low-molecular-weight hydrophilic drugs, such as doxorubicin (DOX), are not suitable for intratumoral injection because the release will complete within one day. In this study, liposomal doxorubicin (LipDOX) was added into the hydrogel to form a novel thermosensitive formulation which prolonged the sustained release of DOX. DOX+C/GP (doxorubicin in chitosan/β-glycerophosphate) was prepared to compare with LipDOX+C/GP (liposomal doxorubicin in chitosan/β-glycerophosphate hydrogel). The particle size of DOX-loaded liposome was 94.2nm and the encapsulation efficiency of DOX was near 98%. In vitro release experiments, the release of DOX in both DOX+C/GP group and LipDOX+C/GP group increased along with the increasing pH of buffers. However, the LipDOX+C/GP group with lower initial burst release had a much longer releasing duration than DOX+C/GP group (21days vs. 24h). In vitro and in vivo antitumor experiments demonstrated that LipDOX+C/GP group had better antineoplastic effect and less toxicity than DOX+C/GP group. Pharmacokinetics study showed LipDOX+C/GP exhibited a higher AUC0-t and longer MRT than DOX+C/GP in blood and tumor, which indicated that LipDOX+C/GP obtained an enhanced antitumor activity compared with DOX+C/GP. In addition, the lower distribution index (the ratio of AUC of normal tissue/AUC of tumor tissue) of the LipDOX+C/GP implied it had lower toxicity to normal tissues than DOX+C/GP. Therefore, the novel thermosensitive hydrogel formulation was potential for clinical application in cancer treatment. PMID:27388491

  14. Bile salt liposomes for enhanced lymphatic transport and oral bioavailability of paclitaxel.

    Science.gov (United States)

    Zhang, Bin; Xue, Aiying; Zhang, Chen; Yu, Jinlong; Chen, Wen; Sun, Deqing

    2016-06-01

    Paclitaxel (PTX), a BCS class IV drug that is characterized by its poor solubility and is a substrate for P-glycoprotein, is one of the most widely used antineoplastic agents. However, oral administration of PTX for chemotherapy is highly challenging. The aim of this study was to develop bile-salt liposomes (BS-Lips) to enhance the absorption of PTX and thus improve its therapeutic outcome. The BS-Lips were prepared by the thin-film hydration method and characterized in terms of particle size and morphology. Drug release and in vitro stability in simulated gastrointestinal fluids and in media of different pH values were evaluated, as well as in vivo performance, including antitumor activity and pharmacokinetics in rats, with the plasma concentrations determined by a HPLC method. The PTX-loaded BS-Lips were successfully prepared with a diameter of approximately 150 nm and an entrapment efficiency of greater than 90 percent. Moreover, the BS-Lips were not affected by gastrointestinal enzymes or pH alternation, as evident from the unchanged particle size and the drug retained in BS-Lips after 6 h incubation. The insertion of bile salt into the lipid layer of liposomes increased the lymphatic transport of PTX by twofold. Importantly, BS-Lips increased the oral bioavailability of PTX by 2.5 and 4-fold, respectively, compared with conventional liposomes (Lips) and Taxol (free drug), thereby displaying a better inhibition of tumor growth that was similar to the group injected intravenously with Taxol. In conclusion, the BS-Lips represent promising vehicles for the oral delivery of PTX, thereby enabling an intravenous-to-oral switch for cancer chemotherapy. PMID:27455550

  15. Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators

    Directory of Open Access Journals (Sweden)

    Signe Tandrup Schmidt

    2016-03-01

    Full Text Available 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 for which no effective vaccines exist. The subunit vaccine technology exploits pathogen subunits as antigens, e.g., recombinant proteins or synthetic peptides, allowing for highly specific immune responses against the pathogens. However, such antigens are usually not sufficiently immunogenic to induce protective immunity, and they are often combined with adjuvants to ensure robust immune responses. Adjuvants are capable of enhancing and/or modulating immune responses by exposing antigens to antigen-presenting cells (APCs concomitantly with conferring immune activation signals. Few adjuvant systems have been licensed for use in human vaccines, and they mainly stimulate humoral immunity. Thus, there is an unmet demand for the development of safe and efficient adjuvant systems that can also stimulate cell-mediated immunity (CMI. Adjuvants constitute a heterogeneous group of compounds, which can broadly 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. Immunostimulators represent highly diverse classes of molecules, e.g., lipids, nucleic acids, proteins and peptides, and they are ligands for pattern-recognition receptors (PRRs, which are differentially expressed on APC subsets. Different formulation strategies might thus be required for incorporation of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the

  16. Nano-Drugs Based on Nano Sterically Stabilized Liposomes for the Treatment of Inflammatory Neurodegenerative Diseases.

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    Keren Turjeman

    Full Text Available The present study shows the advantages of liposome-based nano-drugs as a novel strategy of delivering active pharmaceutical ingredients for treatment of neurodegenerative diseases that involve neuroinflammation. We used the most common animal model for multiple sclerosis (MS, mice experimental autoimmune encephalomyelitis (EAE. The main challenges to overcome are the drugs' unfavorable pharmacokinetics and biodistribution, which result in inadequate therapeutic efficacy and in drug toxicity (due to high and repeated dosage. We designed two different liposomal nano-drugs, i.e., nano sterically stabilized liposomes (NSSL, remote loaded with: (a a "water-soluble" amphipathic weak acid glucocorticosteroid prodrug, methylprednisolone hemisuccinate (MPS or (b the amphipathic weak base nitroxide, Tempamine (TMN. For the NSSL-MPS we also compared the effect of passive targeting alone and of active targeting based on short peptide fragments of ApoE or of β-amyloid. Our results clearly show that for NSSL-MPS, active targeting is not superior to passive targeting. For the NSSL-MPS and the NSSL-TMN it was demonstrated that these nano-drugs ameliorate the clinical signs and the pathology of EAE. We have further investigated the MPS nano-drug's therapeutic efficacy and its mechanism of action in both the acute and the adoptive transfer EAE models, as well as optimizing the perfomance of the TMN nano-drug. The highly efficacious anti-inflammatory therapeutic feature of these two nano-drugs meets the criteria of disease-modifying drugs and supports further development and evaluation of these nano-drugs as potential therapeutic agents for diseases with an inflammatory component.

  17. Luminescent liposome labeling technology with PKH-26 solution and absorption and distribution assessment of lipid multilammelar vesicles and small liposomes in liver following intravenous administration

    International Nuclear Information System (INIS)

    This study examined the possibility to form liposomal compositions containing PKH-26 fluorescent dye and to use those compositions in order to assess absorption and tissue distribution of the liposomes in rat liver. Liposomal compositions consisted of egg lecithin and cholesterol (Sigma) in a 7:5 ratio, respectively. The dye was incorporated into the lipid layer while preparing multilammelar vesicles with the extruder. The obtained labeled liposomal compositions allowed to quantitatively assess how the vesicles are absorbed by the liver and visualize the dye distribution in different liver cells. The study presents the data on the absorption and distribution of the dye in the liver, according to the size of the lipid vesicles, 1, 2 and 24 hours after the intravenous administration. Key words : luminescent labeling, absorption of the liposomes, visualization of the liposomes, liposomal distribution in the cells, PKH -26, liver

  18. Nanoformulation of Geranylgeranyltransferase-I Inhibitors for Cancer Therapy: Liposomal Encapsulation and pH-Dependent Delivery to Cancer Cells.

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    Jie Lu

    Full Text Available Small molecule inhibitors against protein geranylgeranyltransferase-I such as P61A6 have been shown to inhibit proliferation of a variety of human cancer cells and exhibit antitumor activity in mouse models. Development of these inhibitors could be dramatically accelerated by conferring tumor targeting and controlled release capability. As a first step towards this goal, we have encapsulated P61A6 into a new type of liposomes that open and release cargos only under low pH condition. These low pH-release type liposomes were prepared by adjusting the ratio of two types of phospholipid derivatives. Loading of geranylgeranyltransferase-I inhibitor (GGTI generated liposomes with average diameter of 50-100 nm. GGTI release in solution was sharply dependent on pH values, only showing release at pH lower than 6. Release of cargos in a pH-dependent manner inside the cell was demonstrated by the use of a proton pump inhibitor Bafilomycin A1 that Increased lysosomal pH and inhibited the release of a dye carried in the pH-liposome. Delivery of GGTI to human pancreatic cancer cells was demonstrated by the inhibition of protein geranylgeranylation inside the cell and this effect was blocked by Bafilomycin A1. In addition, GGTI delivered by pH-liposomes induced proliferation inhibition, G1 cell cycle arrest that is associated with the expression of cell cycle regulator p21CIP1/WAF1. Proliferation inhibition was also observed with various lung cancer cell lines. Availability of nanoformulated GGTI opens up the possibility to combine with other types of inhibitors. To demonstrate this point, we combined the liposomal-GGTI with farnesyltransferase inhibitor (FTI to inhibit K-Ras signaling in pancreatic cancer cells. Our results show that the activated K-Ras signaling in these cells can be effectively inhibited and that synergistic effect of the two drugs is observed. Our results suggest a new direction in the use of GGTI for cancer therapy.

  19. Liquid-solid extraction of cationic metals by cationic amphiphiles

    International Nuclear Information System (INIS)

    In the field of selective separation for recycling of spent nuclear fuel, liquid-liquid extraction processes are widely used (PUREX, DIAMEX..) in industrial scale. In order to guarantee a sustainable nuclear energy for the forthcoming generations, alternative reprocessing techniques are under development. One of them bases on the studies from Heckmann et al in the 80's and consists in selectively precipitating actinides from aqueous waste solutions by cationic surfactants (liquid-solid extraction). This technique has some interesting advantages over liquid-liquid extraction techniques, because several steps are omitted like stripping or solvent washing. Moreover, the amount of waste is decreased considerably, since no contaminated organic solvent is produced. In this thesis, we have carried out a physico-chemical study to understand the specific interactions between the metallic cations with the cationic surfactant. First, we have analysed the specific effect of the different counter-ions (Cl-, NO3-, C2O42-) and then the effect of alkaline cations on the structural properties of the surfactant aggregation in varying thermodynamical conditions. Finally, different multivalent cations (Cu2+, Zn2+, UO22+, Fe3+, Nd3+, Eu3+, Th4+) were considered; we have concluded that depending on the anionic complex of these metals formed in acidic media, we can observe either an adsorption at the micellar interface or not. This adsorption has a large influence of the surfactant aggregation properties and determines the limits of the application in term of ionic strength, temperature and surfactant concentration. (author)

  20. Combination Approach of YSA Peptide Anchored Docetaxel Stealth Liposomes with Oral Antifibrotic Agent for the Treatment of Lung Cancer.

    Science.gov (United States)

    Patel, Ketan; Doddapaneni, Ravi; Sekar, Vasanthakumar; Chowdhury, Nusrat; Singh, Mandip

    2016-06-01

    Therapeutic efficacy of nanocarriers can be amplified by active targeting and overcoming the extracellular matrix associated barriers of tumors. The aim of the present study was to investigate the effect of oral antifibrotic agent (telmisartan) on tumor uptake and anticancer efficacy of EphA2 receptor targeted liposomes. Docetaxel loaded PEGylated liposomes (DPL) functionalized with nickel chelated phospholipid were prepared using a modified hydration method. DPL were incubated with various concentrations of histidine tagged EphA2 receptor specific peptide (YSA) to optimize particle size, zeta potential, and percentage YSA binding. Cellular uptake studies using various endocytosis blockers revealed that a caveolae dependent pathway was the major route for internalization of YSA anchored liposomes of docetaxel (YDPL) in A549 lung cancer cell line. Hydrodynamic diameter and zeta potential of optimized YDPL were 157.3 ± 11.8 nm and -3.64 mV, respectively. Orthotopic lung tumor xenograft (A549) bearing athymic nude mice treated with oral telmisartan (5 mg/kg) for 2 days showed significantly (p cancer. PMID:27070720

  1. Low-visibility light-intensity laser-triggered release of entrapped calcein from 1,2-bis (tricosa-10,12-diynoyl-sn-glycero-3-phosphocholine liposomes is mediated through a type I photoactivation pathway

    Directory of Open Access Journals (Sweden)

    Yavlovich A

    2013-07-01

    Full Text Available Amichai Yavlovich,1,* Mathias Viard,1,2,* Kshitij Gupta,1,* Jessica Sine,1,* Mylinh Vu,1 Robert Blumenthal,1 Darrell B Tata,3 Anu Puri1,*1Center for Cancer Research Nanobiology Program, National Cancer Institute, Frederick, MD, USA; 2Basic Science Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA; 3Centre for Devices and Radiological Health (CDRH/Office of Science and Engineering Laboratories(OSEL/Division of Physics, US Food and Drug Administration, White Oak, MD, USA*These authors contributed equally to this workAbstract: We recently reported on the physical characteristics of photo-triggerable liposomes containing dipalmitoylphosphatidylcholine (DPPC, and 1,2-bis (tricosa-10,12-diynoyl-sn-glycero-3-phosphocholine (DC8,9PC carrying a photo agent as their payload. When exposed to a low-intensity 514 nm wavelength (continuous-wave laser light, these liposomes were observed to release entrapped calcein green (Cal-G; Ex/Em 490/517 nm but not calcein blue (Cal-B; Ex/Em 360/460 nm. In this study, we have investigated the mechanism for the 514 nm laser-triggered release of the Cal-G payload using several scavengers that are known specifically to inhibit either type I or type II photoreaction pathways. Liposomes containing DPPC:DC8,9PC: distearoylphosphatidylethanolamine (DSPE-polyethylene glycol (PEG-2000 (86:10:04 mole ratio were loaded either with fluorescent (calcein or nonfluorescent (3H-inulin aqueous markers. In addition, a non-photo-triggerable formulation (1-palmitoyl-2-oleoyl phosphatidylcholine [POPC]:DC8,9PC:DSPE-PEG2000 was also studied with the same payloads. The 514 nm wavelength laser exposure on photo-triggerable liposomes resulted in the release of Cal-G but not that of Cal-B or 3H-inulin, suggesting an involvement of a photoactivated state of Cal-G due to the 514 nm laser exposure. Upon 514 nm laser exposures, substantial hydrogen peroxide (H2O2, ≈100 µM levels were detected from

  2. Sulfometuron incorporation in cationic micelles adsorbed on montmorillonite.

    Science.gov (United States)

    Mishael, Yael Golda; Undabeytia, Tomas; Rytwo, Giora; Papahadjopoulos-Sternberg, Brigitte; Rubin, Baruch; Nir, Shlomo

    2002-05-01

    The aim of this study was to understand the interactions between alkylammonium cations present as monomers and micelles and a clay mineral, montmorillonite, to develop slow release formulations of anionic herbicides, such as sulfometuron (SFM) whose leaching in soils is an environmental and economic problem. In the proposed formulation the herbicide is incorporated in positively charged micelles of quaternary amine cations, which in turn adsorb on the negatively charged clay. The adsorption of hexadecyltrimethylammonium (HDTMA) and octadecyltrimethylammonium (ODTMA) on montmorillonite was studied above and below their critical micelle concentrations (CMC). At concentrations above the CMC, the loading exceeded the clay's cation exchange capacity (CEC) and indicated higher affinity of the cation with the longer alkyl chain. An adsorption model could adequately simulate adsorption at concentrations below the CMC, and yield fair predictions for the effect of ionic strength. The model indicated that above the CMC adsorbed micelles contributed significantly to the amount of ODTMA adsorbed. Evidence for adsorption of ODTMA micelles on montmorillonite was provided by X-ray diffraction, freeze-fracture electron microscopy, and dialysis bag measurements. SFM was not adsorbed directly on the clay mineral, and adsorbed at low levels, when the organic cation was adsorbed as monomers. In contrast, a large fraction of SFM adsorbed on the clay mineral when incorporated in micelles that adsorbed on the clay. PMID:11982411

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

    International Nuclear Information System (INIS)

    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, 122Sb and 124Sb, 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)

  4. 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)

  5. Probing mechanical properties of liposomes using acoustic sensors.

    Science.gov (United States)

    Melzak, Kathryn A; Bender, Florian; Tsortos, Achilleas; Gizeli, Electra

    2008-08-19

    Acoustic devices were employed to characterize variations in the mechanical properties (density and viscoelasticity) of liposomes composed of 1-oleoyl-2-palmitoyl- sn-glycero-3-phosphocholine (POPC) and cholesterol. Liposome properties were modified in three ways. In some experiments, the POPC/cholesterol ratio was varied prior to deposition on the device surface. Alternatively, the ratio was changed in situ via either insertion of cholesterol or removal of cholesterol with beta-cyclodextrin. This was done for liposomes adsorbed directly on the device surface and for liposomes attached via a biotin-terminated poly(ethylene glycol) linker. The acoustic measurements make use of two simultaneous time-resolved signals: one signal is related to the velocity of the acoustic wave, while the second is related to dissipation of acoustic energy. Together, they provide information not only about the mass (or density) of the probed medium but also about its viscoelastic properties. The cholesterol-induced increase in the surface density of the lipid bilayer was indeed observed in the acoustic data, but the resulting change in signal was larger than expected from the change in surface density. In addition, increasing the bilayer resistance to stretching was found to lead to a greater dissipation of the acoustic energy. The acoustic response is assessed in terms of the possible distortions of the liposomes and the known effects of cholesterol on the mechanical properties of the lipid bilayer that encloses the aqueous core of the liposome. To aid the interpretation of the acoustic response, it is discussed how the above changes in the lipid bilayer will affect the effective viscoelastic properties of the entire liposome/solvent film on the scale of the acoustic wavelength. It was found that the acoustic device is very sensitive to the mechanical properties of lipid vesicles; the response of the acoustic device is explained, and the basic underlying mechanisms of interaction are

  6. Enhanced transdermal delivery of diclofenac sodium via conventional liposomes, ethosomes, and transfersomes.

    Science.gov (United States)

    Ghanbarzadeh, Saeed; Arami, Sanam

    2013-01-01

    The aim of this study was to improve the transdermal permeation of Diclofenac sodium, a poorly water-soluble drug, employing conventional liposomes, ethosomes, and transfersomes. The prepared formulations had been characterized for the loaded drug amount and vesicle size. The prepared vesicular systems were incorporated into 1% Carbopol 914 gel, and a survey of in vitro drug release and drug retention into rat skin has been done on them using a modified Franz diffusion cell. The cumulative amount of drug permeated after 24 h, flux, and permeability coefficient were assessed. Stability studies were performed for three months. The size of vesicles ranged from 145 to 202 nm, and the encapsulation efficiency of the Diclofenac sodium was obtained between 42.61% and 51.72%. The transfersomes and ethosomes provided a significantly higher amount of cumulative permeation, steady state flux, permeability coefficient, and residual drug into skin compared to the conventional liposomes, conventional gel, or hydroethanolic solution. The in vitro release data of all vesicular systems were well fit into Higuchi model (RSD > 0.99). Stability tests indicated that the vesicular formulations were stable over three months. Results revealed that both ethosome and transfersome formulations can act as drug reservoir in skin and extend the pharmacologic effects of Diclofenac sodium. PMID:23936825

  7. Enhanced Transdermal Delivery of Diclofenac Sodium via Conventional Liposomes, Ethosomes, and Transfersomes

    Directory of Open Access Journals (Sweden)

    Saeed Ghanbarzadeh

    2013-01-01

    Full Text Available The aim of this study was to improve the transdermal permeation of Diclofenac sodium, a poorly water-soluble drug, employing conventional liposomes, ethosomes, and transfersomes. The prepared formulations had been characterized for the loaded drug amount and vesicle size. The prepared vesicular systems were incorporated into 1% Carbopol 914 gel, and a survey of in vitro drug release and drug retention into rat skin has been done on them using a modified Franz diffusion cell. The cumulative amount of drug permeated after 24 h, flux, and permeability coefficient were assessed. Stability studies were performed for three months. The size of vesicles ranged from 145 to 202 nm, and the encapsulation efficiency of the Diclofenac sodium was obtained between 42.61% and 51.72%. The transfersomes and ethosomes provided a significantly higher amount of cumulative permeation, steady state flux, permeability coefficient, and residual drug into skin compared to the conventional liposomes, conventional gel, or hydroethanolic solution. The in vitro release data of all vesicular systems were well fit into Higuchi model (RSD > 0.99. Stability tests indicated that the vesicular formulations were stable over three months. Results revealed that both ethosome and transfersome formulations can act as drug reservoir in skin and extend the pharmacologic effects of Diclofenac sodium.

  8. Lipid bilayer elasticity measurements in giant liposomes in contact with a solubilizing surfactant.

    Science.gov (United States)

    Ménager, Christine; Guemghar, Dihya; Perzynski, Régine; Lesieur, Sylviane; Cabuil, Valérie

    2008-05-01

    A new method to probe the modification of the elasticity of phospholipid bilayers is presented. The purpose here concerns the action of a solubilizing surfactant on a vesicle bilayer. This method is based on the measure of the under-field elongation of giant magnetic-fluid-loaded liposomes. The addition of the nonionic surfactant octyl-beta-d-glucopyranoside (OG) to