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Sample records for spontaneously form liposomes

  1. ANTISTAPHYLOCOCCAL ACTIVITY OF LIPOSOMAL FORMS OF LINCOMYCIN

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    Derkach SA

    2015-04-01

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

  2. Oxidative Stability of Marine Phospholipids in the Liposomal Form and Their Applications

    DEFF Research Database (Denmark)

    Lu, Henna Fung Sieng; Nielsen, Nina Skall; Timm-Heinrich, M.

    2011-01-01

    source. Due to their tight intermolecular packing conformation at the sn-2 position and their synergism with α-tocopherol present in MPL extracts, they can form stable liposomes which are attractive ingredients for food or feed applications. However, MPL are still susceptible to oxidation as they contain...... large amounts polyunsaturated fatty acids and application of MPL in food and aquaculture industries is therefore a great challenge for researchers. Hence, knowledge on the oxidative stability of MPL and the behavior of MPL in food and feed systems is an important issue. For this reason, this review...... was undertaken to provide the industry and academia with an overview of (1) the stability of MPL in different forms and their potential as liposomal material, and (2) the current applications and future prospects of MPL in both food and aquaculture industries with special emphasis on MPL in the liposomal form....

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

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    M. A. Kisjakova

    2010-07-01

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

  4. Evaluation of cyclosporine A eye penetration after administration of liposomal or conventional forms in animal model

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    Sara Nikoofal-Sahlabadi

    2013-01-01

    Full Text Available Abstract A lot of researches have investigated the effects of topical cyclosporine A on the eye surface layers’ diseases. By now the main limitation in cyclosporine application is the low permeation of the drug into the posterior segments of the eye. The aim of present study was to formulate high permeable dosage form can be beneficial in the topical treatment of the uveitis. To reach higher corneal drug absorption and drug concentration in the posterior segments of the eye, 3 nanoliposomal formulations containing 0.5 mg/ml cyclosporine A were prepared. Liposomal formulations and the commercial product (Restasis® were instilled in the right and left eyes of the rabbits, respectively. The rabbits were killed in the 3, 7, 14 and 28 days of study and the aqueous humor and vitreous were extracted. Mean size of liposomal formulation number 1, number 2 and number 3 were 107.2 ± 0.7, 129.3±0.9 and 144.8±1.8 nm and their zeta potential were -5.0±1.7, -5.5±2.3 and 44.6±6.2 mV, respectively. Results of ocular analysis showed that the liposomal formulations could increase the concentration of the drug in the aqueous and vitreous like Restasis®. But, in contrast with what has been expected the findings of this study implicate nanoliposomal formulations prepared could not make a significant difference in concentration of the drug in aqueous and vitreous humor compared to Restasis® (anionic microemulsion. In conclusion, we can state that liposomes with the same composition as our formulations are not more efficient than microemulsion for cyclosporine as ophthalmic drug delivery.

  5. Liposomal formulation of α-tocopheryl maleamide: In vitro and in vivo toxicological profile and anticancer effect against spontaneous breast carcinomas in mice

    International Nuclear Information System (INIS)

    Turanek, Jaroslav; Wang Xiufang; Knoetigova, Pavlina; Koudelka, Stepan; Dong Lanfeng; Vrublova, Eva; Mahdavian, Elahe; Prochazka, Lubomir; Sangsura, Smink; Vacek, Antonin; Salvatore, Brian A.; Neuzil, Jiri

    2009-01-01

    The vitamin E analogue α-tocopheryl succinate (α-TOS) is an efficient anti-cancer drug. Improved efficacy was achieved through the synthesis of α-tocopheryl maleamide (α-TAM), an esterase-resistant analogue of α-tocopheryl maleate. In vitro tests demonstrated significantly higher cytotoxicity of α-TAM towards cancer cells (MCF-7, B16F10) compared to α-TOS and other analogues prone to esterase-catalyzed hydrolysis. However, in vitro models demonstrated that α-TAM was cytotoxic to non-malignant cells (e.g. lymphocytes and bone marrow progenitors). Thus we developed lyophilized liposomal formulations of both α-TOS and α-TAM to solve the problem with cytotoxicity of free α-TAM (neurotoxicity and anaphylaxis), as well as the low solubility of both drugs. Remarkably, neither acute toxicity nor immunotoxicity implicated by in vitro tests was detected in vivo after application of liposomal α-TAM, which significantly reduced the growth of cancer cells in hollow fiber implants. Moreover, liposomal formulation of α-TAM and α-TOS each prevented the growth of tumours in transgenic FVB/N c-neu mice bearing spontaneous breast carcinomas. Liposomal formulation of α-TAM demonstrated anti-cancer activity at levels 10-fold lower than those of α-TOS. Thus, the liposomal formulation of α-TAM preserved its strong anti-cancer efficacy while eliminating the in vivo toxicity found of the free drug applied in DMSO. Liposome-based targeted delivery systems for analogues of vitamin E are of interest for further development of efficient and safe drug formulations for clinical trials.

  6. EFFECT OF CURCUMIN LIPOSOMAL FORM ON ANGIOTENSIN CONVERTING ACTIVITY, CYTOKINES AND COGNITIVE CHARACTERISTICS OF THE RATS WITH ALZHEIMER’S DISEASE MODEL

    OpenAIRE

    V.V.; S.М.

    2015-01-01

    The purpose of the study was the investigation of curcumin liposome form effect on angiotensinconverting enzyme activity, cytokines and mnestic features of rats with experimental model of Alzheimer’s disease. In the animals with intrahippocampal injection of А42_Human, nasal therapy with curcumin liposome form was used. Cytokine concentration and angiotensin converting enzyme activity in brain regions (cerebral cortex and hippocampus) and in blood serum as well as indicators of conditioned a...

  7. Influence of liposome forms of the rhenium compounds and cis-platin on thiol-disulfide coefficient in the rats’ blood

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    I. V. Klenina

    2007-12-01

    Full Text Available Thiol-disulfide coefficient (TDC and its different modifications in model in vivo were studied. Introduction of the liposome forms of cluster rhenium compounds with organic ligands (CROL leads to both TDC increasing and to the constancy of the TDC. Thus, CROLs aren’t toxic agents and some compounds could mobilize organisms’ thiol defence system. Liposome form of cis-platin leads to the TDC decreasing. Important CROL capacities for its future medical treatment practice were shown.

  8. Liposomes and lipid disks traverse the BBB and BBTB as intact forms as revealed by two-step Förster resonance energy transfer imaging

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    Tongcheng Dai

    2018-03-01

    Full Text Available The blood–brain barrier (BBB and the blood–brain tumor barrier (BBTB prevent drug and nano-drug delivery systems from entering the brain. However, ligand-mediated nano-drug delivery systems have significantly enhanced the therapeutic treatment of glioma. In this study we investigated the mechanism especially the integrity of liposomes and lipid disks while traversing the BBB and BBTB both in vitro and in vivo. Fluorophores (DiO, DiI and DiD were loaded into liposomes and lipid disks to form Förster resonance energy transfer (FRET nano-drug delivery systems. Using brain capillary endothelial cells as a BBB model, we show that liposomes and disks are present in the cytoplasm as their intact forms and traverse the BBB with a ratio of 0.68‰ and 1.67‰, respectively. Using human umbilical vein endothelial cells as BBTB model, liposomes and disks remained intact and traversed the BBTB with a ratio of 2.31‰ and 8.32‰ at 3 h. Ex vivo imaging and immunohistochemical results revealed that liposomes and disks could traverse the BBB and BBTB in vivo as intact forms. In conclusion, these observations explain in part the mechanism by which nano-drug delivery systems increase the therapeutic treatment of glioma. KEY WORDS: Liposomes, Disks, Intact form, BBB, BBTB, FRET

  9. Cellular microtissues spontaneously formed in a microfabricated device for angiongenesis

    NARCIS (Netherlands)

    le Gac, Severine; Rivron, N.C.; Rivron, Nicolas; Wijnperle, Daniël; Wijnperle, Daniel; van Blitterswijk, Clemens; van den Berg, Albert; Locascio, L.E.; Gaitan, M.; Paegel, B.M.; Ross, D.J.; Vreeland, W.N.

    2008-01-01

    We report here on a microdevice for the spontaneous and simultaneous formation of microtissues -or microscale spheroids- in a fast, controlled and reproducible way. Spheroids are relevant constructs for tissue engineering applications, and notably for studying the process of angiogenesis which is of

  10. EFFECT OF CURCUMIN LIPOSOMAL FORM ON ANGIOTENSIN CONVERTING ACTIVITY, CYTOKINES AND COGNITIVE CHARACTERISTICS OF THE RATS WITH ALZHEIMER’S DISEASE MODEL

    Directory of Open Access Journals (Sweden)

    V.V.

    2015-12-01

    Full Text Available The purpose of the study was the investigation of curcumin liposome form effect on angiotensinconverting enzyme activity, cytokines and mnestic features of rats with experimental model of Alzheimer’s disease. In the animals with intrahippocampal injection of Аβ42_Human, nasal therapy with curcumin liposome form was used. Cytokine concentration and angiotensin converting enzyme activity in brain regions (cerebral cortex and hippocampus and in blood serum as well as indicators of conditioned avoidance response were registered. It was found that as a result of curcumin therapy the rats with Alzheimer’s disease had suppressed cytokine and angiotensin converting enzyme activities and recovered mnestic indices. Nasal therapy with curcumin liposome form gave reduction of angiotensin-converting enzyme activity and anti-cytokine effect in the target regions of the brain (cerebral cortex and hippocampus, which helped the rats mnestic features and memory recovery.

  11. Canonical forms of tensor representations and spontaneous symmetry breaking

    International Nuclear Information System (INIS)

    Cummins, C.J.

    1986-01-01

    An algorithm for constructing canonical forms for any tensor representation of the classical compact Lie groups is given. This method is used to find a complete list of the symmetry breaking patterns produced by Higgs fields in the third-rank antisymmetric representations of U(n), SU(n) and SO(n) for n<=7. A simple canonical form is also given for kth-rank symmetric tensor representations. (author)

  12. Spontaneous activity in the developing mammalian retina: Form and function

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    Butts, Daniel Allison

    Spontaneous neuronal activity is present in the immature mammalian retina during the initial stages of visual system development, before the retina is responsive to light. This activity consists of bursts of action potentials fired by retinal ganglion cells, and propagates in a wavelike manner across the inner plexiform layer of the retina. Unlike waves in other neural systems, retinal waves have large variability in both their rate and direction of propagation, and individual waves only propagate across small regions of the retina. The unique properties of retinal activity arise from dynamic processes within the developing retina, and produce characteristic spatiotemporal properties. These spatiotemporal properties are of particular interest, since they are believed to play a role in visual system development. This dissertation addresses the complex spatiotemporal patterning of the retinal waves from two different perspectives. First, it proposes how the immature circuitry of the developing retina generates these patterns of activity. In order to reproduce the distinct spatiotemporal properties observed in experiments, a model of the immature retinal circuitry must meet certain requirements, which are satisfied by a coarse-grained model of the developing retina that we propose. Second, this dissertation addresses how the particular spatiotemporal patterning of the retinal waves provides information to the rest of the visual system and, as a result, can be used to guide visual system development. By measuring the properties of this information, we place constraints on the developmental mechanisms that use this activity, and show how the particular spatiotemporal properties of the retinal waves provide this information. Together, this dissertation demonstrates how the apparent complexity of retinal wave patterning can be understood both through the immature circuitry that generates it, and through the developmental mechanisms that may use it. The first three

  13. A simple passive equilibration method for loading carboplatin into pre-formed liposomes incubated with ethanol as a temperature dependent permeability enhancer.

    Science.gov (United States)

    Wehbe, Moe; Malhotra, Armaan; Anantha, Malathi; Roosendaal, Jeroen; Leung, Ada W Y; Plackett, David; Edwards, Katarina; Gilabert-Oriol, Roger; Bally, Marcel B

    2017-04-28

    A passive equilibration method which relies on addition of candidate drugs to pre-formed liposomes is described as an alternative method for preparing liposome encapsulated drugs. The method is simple, rapid and applicable to liposomes prepared with high (45mol%) or low (liposomes, (ii) addition of the candidate drug to the liposomes in combination with a permeability enhancing agent, (iii) incubation at a temperature that facilitates diffusion of the added compound across the lipid bilayer, and (iv) quenching the enhanced membrane permeability by reduction in temperature and/or removal of the permeabilization enhancer. The method is fully exemplified here using ethanol as the permeabilization enhancer and carboplatin (CBDCA) as the drug candidate. It is demonstrated that ethanol can be added to liposomes prepared with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and Cholesterol (Chol) (55:45mol ratio) in amounts up to 30% (v/v) with no change in liposome size, even when incubated at temperatures>60°C. Super-saturated solutions of CBDCA (40mg/mL) can be prepared at 70°C and these are stable in the presence of ethanol even when the temperature is reduced to liposomes in the presence of 30% (v/v) ethanol at 60°C. When the pre-formed liposomes are mixed with ethanol (30% v/v) at or below 40°C, the encapsulation efficiency is reduced by an order of magnitude. The method was also applied to liposomes prepared from other compositions include a cholesterol free formulations (containing 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] (DSPE-PEG 2000 )) and a low Chol (stability in vitro and in vivo. The cytotoxic activity of CBDCA was unaffected when prepared in this manner and the resultant formulations exhibited good stability in vitro and in vivo. Pharmacokinetics studies in CD-1 mice indicated that the resulting formulations increased the circulation half life of the associated CBDCA significantly (AUC 0-24h of CBDCA=0.016

  14. Liposome formation in microgravity

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    Claassen, D. E.; Spooner, B. S.

    Liposomes are artificial vesicles with a phospholipid bilayer membrane. The formation of liposomes is a self-assembly process that is driven by the amphipathic nature of phospholipid molecules and can be observed during the removal of detergent from phospholipids dissolved in detergent micelles. As detergent concentration in the mixed micelles decreases, the non-polar tail regions of phospholipids produce a hydrophobic effect that drives the micelles to fuse and form planar bilayers in which phospholipids orient with tail regions to the center of the bilayer and polar head regions to the external surface. Remaining detergent molecules shield exposed edges of the bilayer sheet from the aqueous environment. Further removal of detergent leads to intramembrane folding and membrane vesiculation, forming liposomes. We have observed that the formation of liposomes is altered in microgravity. Liposomes that were formed at 1-g did not exceed 150 nm in diameter, whereas liposomes that were formed during spaceflight exhibited diameters up to 2000 nm. Using detergent-stabilized planar bilayers, we determined that the stage of liposome formation most influenced by gravity is membrane vesiculation. In addition, we found that small, equipment-induced fluid disturbances increased vesiculation and negated the size-enhancing effects of microgravity. However, these small disturbances had no effect on liposome size at 1-g, likely due to the presence of gravity-induced buoyancy-driven fluid flows (e.g., convection currents). Our results indicate that fluid disturbances, induced by gravity, influence the vesiculation of membranes and limit the diameter of forming liposomes.

  15. Liposomal formulation of alpha-tocopheryl maleamide: In vitro and in vivo toxicological profile and anticancer effect against spontaneous breast carcinomas in mice

    Czech Academy of Sciences Publication Activity Database

    Turánek, J.; Wang, X. F.; Knötigová, P.; Koudelka, Š.; Dong, L. F.; Vrublová, E.; Mahdavian, E.; Procházka, L.; Sangsura, S.; Vacek, A.; Salvatore, B. A.; Neužil, Jiří

    2009-01-01

    Roč. 237, č. 3 (2009), s. 249-257 ISSN 0041-008X R&D Projects: GA AV ČR KAN200520703; GA AV ČR(CZ) IAA500520602 Institutional research plan: CEZ:AV0Z50520701 Keywords : Liposome * apoptosis * vitamin E analogues Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 3.359, year: 2009

  16. Neurolinguistic features of spontaneous language production dissociate three forms of neurodegenerative disease: Alzheimer's, Huntington's, and Parkinson's.

    Science.gov (United States)

    Illes, J

    1989-11-01

    An analysis of the temporal (prospective) form (silent and filled hesitations, repetitions, incomplete phrases, context-related comments, interjections), syntactic form, and lexical (retrospective) form (verbal deviations, open and closed class phrases) of spontaneous language production of early and middle stage Alzheimer's, Huntington's, and Parkinson's patients was made. Results showed that the language structure was disrupted in each disease, but in different ways. Temporal interruptions of varying types were frequent in the language of Alzheimer's and Huntington's Disease patients; only long-duration silent hesitations were frequent in Parkinson's language samples. Syntactic complexity was reduced in Huntington's Disease. Verbal paraphasias were found in both the language of Alzheimer's patients, as well as moderately advanced Huntington's patients. Closed class phrases were predominant in the language of Alzheimer's patients and Huntington's patients, and open class phrases in the language of Parkinson's patients. Taken together, the results suggest that (1) there is a unique neurolinguistic profile for spontaneous language production for each neurodegenerative disease, (2) pathology of the neostriatum disrupts syntactic organization, (3) adaptive strategies are used to cope with verbal and speech-motor difficulties, and (4) adaptive strategies fail to be effective with increasing disease severity.

  17. The spontaneous use of Hebrew verb forms by Israeli preschool children with and without sli The spontaneous use of Hebrew verb forms by Israeli preschool children with and without sli

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    Esther Dromi

    2008-04-01

    Full Text Available In this article we present findings on the spontaneous use of verb forms by preschool Hebrew speaking children who were diagnosed as SLI (Specific Language Impairment and by younger normally developing (ND - L children who were matched by language level to the SLI group. We evaluate the spontaneous use of verb forms in obligatory contexts and compare it with previous results on the morphological abilities of SLI and ND-L children in elicitation tasks. This article reviews previous published findings on verb elicitation tasks and report new data on the use of Hebrew verb forms in spontaneous language samples. Results indicate that HSLI (High Specific Language Impairment children produce verb forms as successfully as their utterance length in morphemes lead to expect. This is especially true when the verb forms they use belong to simple verb patterns. The difficulty HSLI children face with respect to verb morphology is selective rather than sweeping, and it is not evident in the spontaneous speech samples because in this context children avoid producing complex verb forms. The article highlights the position that in languages with rich inflectional morphology it is always useful to combine elicited and spontaneous research methods for studying the productive morphological abilities of young children. In this article we present findings on the spontaneous use of verb forms by preschool Hebrew speaking children who were diagnosed as SLI (Specific Language Impairment and by younger normally developing (ND - L children who were matched by language level to the SLI group. We evaluate the spontaneous use of verb forms in obligatory contexts and compare it with previous results on the morphological abilities of SLI and ND-L children in elicitation tasks. This article reviews previous published findings on verb elicitation tasks and report new data on the use of Hebrew verb forms in spontaneous language samples. Results indicate that HSLI (High

  18. EFFECTS OF SILVER NANOPARTICLES IN SOLUTION AND LIPOSOMAL FORM ON SOME BLOOD PARAMETERS IN FEMALE RABBITS DURING FERTILIZATION AND EARLY EMBRYONIC DEVELOPMENT

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    Vasyl Syrvatka

    2014-02-01

    Full Text Available Silver nanoparticles are the most rapidly growing classes of nanoproducts. In this study, we investigated the influence of subcutaneous injections of silver nanoparticles in solution and in liposomal form on hematological and biochemical parameters of blood of New Zealand White rabbits during hormonal treatment, fertilization and early embryonic development. The females treated by free silver nanoparticles and silver nanoparticles in liposomal form received silver at a dose of 10 µg/kg/day in 5 % glucose solution during 28 days. Blood sampling was done four times: the day before the compounds administration; on day 7 after the compounds administration; in the period after hormonal induction and fertilization and on the 14th day of pregnancy. Our results showed changes in some biochemical (lactate dehydrogenase activities, progesterone and estradiol concentration, malondialdehyde level, etc. and hematological (hematocrit, mean cell volume, mean corpuscular hemoglobin concentration, etc. parameters under the influence of hormonal treatment and pregnancy. The concentration of progesterone showed significantly higher values (P˂0.05 on GDs 1 in S group than in C group. The percentage of neutrophils was significantly higher in SG rabbits after 7 days of silver nanoparticles administration than that in the CG. There were no significant changes in red blood cells parameters, platelets, and activity of some ferments (ALP, AST, ALT, LDH, GGT between control and silver groups during the entire period of experiment. In conclusion, the hematological and biochemical values of blood obtained in the given study showed that free silver nanoparticles and silver nanoparticles in liposomal form in the investigated concentrations had no toxic effect on hormonal treatment, fertilization and early embryonic development in New Zealand White rabbits.

  19. Terahertz wave generation from spontaneously formed nanostructures in silver nanoparticle ink.

    Science.gov (United States)

    Kato, Kosaku; Takano, Keisuke; Tadokoro, Yuzuru; Nakajima, Makoto

    2016-05-01

    We demonstrate terahertz pulse generation from silver nanoparticle ink, originally developed for printed electronics, under irradiation by femtosecond laser pulses. Using metal nanoparticle ink, metallic nanostructures can be easily made in a large area without lithographic techniques. Terahertz pulses were emitted from the baked ink, having spontaneously formed nanostructures of ∼100  nm. From the results of the baking temperature dependence and the polarization measurement, the terahertz generation is attributed to the nonlinear polarization induced by the enhanced local fields around these nanostructures. This study paves the way for the future development of terahertz emitters which have resonances in both the near-infrared light and the terahertz wave, by combining micrometer-scale structures drawn by an inkjet printer and nanometer-scale structures formed during the baking process.

  20. Representing Representation: Integration between the Temporal Lobe and the Posterior Cingulate Influences the Content and Form of Spontaneous Thought.

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    Jonathan Smallwood

    Full Text Available When not engaged in the moment, we often spontaneously represent people, places and events that are not present in the environment. Although this capacity has been linked to the default mode network (DMN, it remains unclear how interactions between the nodes of this network give rise to particular mental experiences during spontaneous thought. One hypothesis is that the core of the DMN integrates information from medial and lateral temporal lobe memory systems, which represent different aspects of knowledge. Individual differences in the connectivity between temporal lobe regions and the default mode network core would then predict differences in the content and form of people's spontaneous thoughts. This study tested this hypothesis by examining the relationship between seed-based functional connectivity and the contents of spontaneous thought recorded in a laboratory study several days later. Variations in connectivity from both medial and lateral temporal lobe regions was associated with different patterns of spontaneous thought and these effects converged on an overlapping region in the posterior cingulate cortex. We propose that the posterior core of the DMN acts as a representational hub that integrates information represented in medial and lateral temporal lobe and this process is important in determining the content and form of spontaneous thought.

  1. Nutraceutical delivery systems: resveratrol encapsulation in grape seed oil nanoemulsions formed by spontaneous emulsification.

    Science.gov (United States)

    Davidov-Pardo, Gabriel; McClements, David Julian

    2015-01-15

    The aim of this work was to fabricate nanoemulsions-based delivery systems to encapsulate resveratrol. Nanoemulsions were formed using spontaneous emulsification method: 10% oil phase (grape seed oil plus orange oil) and 10% surfactant (Tween 80) were titrated into 80% aqueous phase. An optimum orange oil-to-grape seed oil ratio of 1:1(w/w) formed small droplets (d ≈ 100 nm) with good stability to droplet growth. The maximum amount of resveratrol that could be dissolved in the oil phase was 120 ± 10 μg/ml. The effect of droplet size on the chemical stability of encapsulated resveratrol was examined by preparing systems with different mean droplet diameters of 220 ± 2; 99 ± 3; and 45 ± 0.4 nm. Encapsulation of resveratrol improved its chemical stability after exposure to UV-light: 88% retention in nanoemulsions compared to 50% in dimethylsulphoxide (DMSO). This study showed that resveratrol could be encapsulated within low-energy nanoemulsion-based delivery systems and protected against degradation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Ligand-Mediated Coating of Liposomes with Human Serum Albumin.

    Science.gov (United States)

    Sato, Hikari; Nakhaei, Elnaz; Kawano, Takahito; Murata, Masaharu; Kishimura, Akihiro; Mori, Takeshi; Katayama, Yoshiki

    2018-02-13

    Coating liposome surfaces with human serum albumin (HSA) can improve the colloidal stability and prevent opsonization. HSA coating via specific binding with alkyl ligands is promising because although the ligand-mediated coating is relatively stable it can spontaneously exchange with fresh HSA. However, to achieve surface coating with HSA, multiple hydrophobic ligands must be exposed to an aqueous medium prior to binding with HSA. This presents a challenge, as hydrophobic ligands tend to be buried in the liposomal membrane. Here we present the first HSA modification of liposome surfaces via alkyl ligands. We found that a relatively short alkyl ligand, or a long alkyl ligand with a terminal carboxylate, could be exposed on the liposome surface without causing aggregation of the liposomes and these ligands could subsequently bind HSA. The resulting HSA-coated liposomes were as inert as conventional PEGylated liposomes in terms of macrophage recognition.

  3. Nanoparticle Stabilized Liposomes for Acne Therapy

    Science.gov (United States)

    Fu, Victoria

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

  4. Photoelectrochemical water splitting and hydrogen generation by a spontaneously formed InGaN nanowall network

    Energy Technology Data Exchange (ETDEWEB)

    Alvi, N. H., E-mail: nhalvi@isom.upm.es, E-mail: r.noetzel@isom.upm.es; Soto Rodriguez, P. E. D.; Kumar, Praveen; Gómez, V. J.; Aseev, P.; Nötzel, R., E-mail: nhalvi@isom.upm.es, E-mail: r.noetzel@isom.upm.es [ISOM Institute for Systems Based on Optoelectronics and Microtechnology, ETSI Telecomunicación, Universidad Politécnica de Madrid, Ciudad Universitaria s/n, 28040 Madrid (Spain); Alvi, A. H. [Department of Physics, Government College University, Faisalabad (Pakistan); Alvi, M. A. [Department of Chemistry, Government College University, Faisalabad (Pakistan); Willander, M. [Department of Science and Technology (ITN), Campus Norrköping, Linköping University, 60174 Norrköping (Sweden)

    2014-06-02

    We investigate photoelectrochemical water splitting by a spontaneously formed In-rich InGaN nanowall network, combining the material of choice with the advantages of surface texturing for light harvesting by light scattering. The current density for the InGaN-nanowalls-photoelectrode at zero voltage versus the Ag/AgCl reference electrode is 3.4 mA cm{sup −2} with an incident-photon-to-current-conversion efficiency (IPCE) of 16% under 350 nm laser illumination with 0.075 W·cm{sup −2} power density. In comparison, the current density for a planar InGaN-layer-photoelectrode is 2 mA cm{sup −2} with IPCE of 9% at zero voltage versus the Ag/AgCl reference electrode. The H{sub 2} generation rates at zero externally applied voltage versus the Pt counter electrode per illuminated area are 2.8 and 1.61 μmol·h{sup −1}·cm{sup −2} for the InGaN nanowalls and InGaN layer, respectively, revealing ∼57% enhancement for the nanowalls.

  5. Light extraction from organic light-emitting diodes enhanced by spontaneously formed buckles

    Science.gov (United States)

    Koo, Won Hoe; Jeong, Soon Moon; Araoka, Fumito; Ishikawa, Ken; Nishimura, Suzushi; Toyooka, Takehiro; Takezoe, Hideo

    2010-04-01

    Most of the light in conventional organic light-emitting diodes is confined to high-refractive-index layers (such as an organic medium, indium tin oxide and glass substrate) resulting in a low light extraction efficiency of ~20% (refs 1,2). Many studies have used wavelength-scale periodic gratings to increase the external efficiency of organic light-emitting diodes. However, the efficiency is only enhanced at particular wavelengths satisfying the Bragg condition. Here, we demonstrate that a quasi-periodic buckling structure with broad distribution and directional randomness can enhance the light extraction efficiency without introducing spectral changes and directionality. Organic light-emitting diodes corrugated by buckles showed improved current and power efficiencies and an electroluminescence spectrum enhanced by at least a factor of two across the entire visible wavelength regime. These buckling patterns are formed spontaneously on elastic materials with a thin metallic film. The buckled organic light-emitting diode devices are practical and attractive for use in fabricating full colour and white organic light-emitting diodes.

  6. Relaxivity of liposomal paramagnetic MRI contrast agents

    NARCIS (Netherlands)

    Strijkers, G. J.; Mulder, W. J. M.; van Heeswijk, R. B.; Frederik, P. M.; Bomans, P.; Magusin, P. C. M. M.; Nicolay, K.

    2005-01-01

    Paramagnetic liposomes, spherical particles formed by a lipid bilayer, are able to accommodate a high payload of Gd-containing lipid and therefore can serve as a highly potent magnetic resonance imaging contrast agent. In this paper the relaxation properties of paramagnetic liposomes were studied as

  7. Human embryonic stem cell-derived neuronal cells form spontaneously active neuronal networks in vitro.

    Science.gov (United States)

    Heikkilä, Teemu J; Ylä-Outinen, Laura; Tanskanen, Jarno M A; Lappalainen, Riikka S; Skottman, Heli; Suuronen, Riitta; Mikkonen, Jarno E; Hyttinen, Jari A K; Narkilahti, Susanna

    2009-07-01

    The production of functional human embryonic stem cell (hESC)-derived neuronal cells is critical for the application of hESCs in treating neurodegenerative disorders. To study the potential functionality of hESC-derived neurons, we cultured and monitored the development of hESC-derived neuronal networks on microelectrode arrays. Immunocytochemical studies revealed that these networks were positive for the neuronal marker proteins beta-tubulin(III) and microtubule-associated protein 2 (MAP-2). The hESC-derived neuronal networks were spontaneously active and exhibited a multitude of electrical impulse firing patterns. Synchronous bursts of electrical activity similar to those reported for hippocampal neurons and rodent embryonic stem cell-derived neuronal networks were recorded from the differentiated cultures until up to 4 months. The dependence of the observed neuronal network activity on sodium ion channels was examined using tetrodotoxin (TTX). Antagonists for the glutamate receptors NMDA [D(-)-2-amino-5-phosphonopentanoic acid] and AMPA/kainate [6-cyano-7-nitroquinoxaline-2,3-dione], and for GABAA receptors [(-)-bicuculline methiodide] modulated the spontaneous electrical activity, indicating that pharmacologically susceptible neuronal networks with functional synapses had been generated. The findings indicate that hESC-derived neuronal cells can generate spontaneously active networks with synchronous communication in vitro, and are therefore suitable for use in developmental and drug screening studies, as well as for regenerative medicine.

  8. Spontaneously formed high-performance charge-transport layers of organic single-crystal semiconductors on precisely synthesized insulating polymers

    Science.gov (United States)

    Makita, Tatsuyuki; Sasaki, Masayuki; Annaka, Tatsuro; Sasaki, Mari; Matsui, Hiroyuki; Mitsui, Chikahiko; Kumagai, Shohei; Watanabe, Shun; Hayakawa, Teruaki; Okamoto, Toshihiro; Takeya, Jun

    2017-04-01

    Charge-transporting semiconductor layers with high carrier mobility and low trap-density, desired for high-performance organic transistors, are spontaneously formed as a result of thermodynamic phase separation from a blend of π-conjugated small molecules and precisely synthesized insulating polymers dissolved in an aromatic solvent. A crystal film grows continuously to the size of centimeters, with the critical conditions of temperature, concentrations, and atmosphere. It turns out that the molecular weight of the insulating polymers plays an essential role in stable film growth and interfacial homogeneity at the phase separation boundary. Fabricating the transistor devices directly at the semiconductor-insulator boundaries, we demonstrate that the mixture of 3,11-didecyldinaphtho[2,3-d:2',3'-d']benzo[1,2-b:4,5-b']dithiophene and poly(methyl methacrylate) with the optimized weight-average molecular weight shows excellent device performances. The spontaneous phase separation with a one-step fabrication process leads to a high mobility up to 10 cm2 V-1 s-1 and a low subthreshold swing of 0.25 V dec-1 even without any surface treatment such as self-assembled monolayer modifications on oxide gate insulators.

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

    Directory of Open Access Journals (Sweden)

    Sandy Gim Ming Ong

    2016-08-01

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

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

    Science.gov (United States)

    Ong, Sandy Gim Ming; Ming, Long Chiau; Lee, Kah Seng; Yuen, Kah Hay

    2016-08-26

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

  11. Spherical domain wall formed by field dynamics of Hawking radiation and spontaneous charging-up of black hole

    International Nuclear Information System (INIS)

    Nagatani, Yukinori

    2004-01-01

    We investigate the Hawking radiation in the gauge Higgs-Yukawa theory. The ballistic model is proposed as an effective description of the system. We find that a spherical domain wall around the black hole is formed by field dynamics rather than thermal phase transition. The formation is a general property of the black hole whose Hawking temperature is equal to or greater than the energy scale of the theory. The formation of the electroweak wall and that of the GUT wall are shown. We also find a phenomenon of the spontaneous charging-up of the black hole by the wall. The Hawking radiation drives a mechanism of the charge transportation into the black hole when C- and CP-violation are assumed. The mechanism can strongly transport the hyper-charge into a black hole of the electroweak scale

  12. Spontaneous activity in electromyography may differentiate certain benign lower motor neuron disease forms from amyotrophic lateral sclerosis.

    Science.gov (United States)

    Jokela, Manu E; Jääskeläinen, Satu K; Sandell, Satu; Palmio, Johanna; Penttilä, Sini; Saukkonen, Annamaija; Soikkeli, Raija; Udd, Bjarne

    2015-08-15

    There is limited data on electromyography (EMG) findings in other motor neuron disorders than amyotrophic lateral sclerosis (ALS). We assessed whether the distribution of active denervation detected by EMG, i.e. fibrillations and fasciculations, differs between ALS and slowly progressive motor neuron disorders. We compared the initial EMG findings of 43 clinically confirmed, consecutive ALS patients with those of 41 genetically confirmed Late-onset Spinal Motor Neuronopathy and 14 Spinal and Bulbar Muscular Atrophy patients. Spontaneous activity was more frequently detected in the first dorsal interosseus and deltoid muscles of ALS patients than in patients with the slowly progressive motor neuron diseases. The most important observation was that absent fibrillations in the first dorsal interosseus muscle identified the benign forms with sensitivities of 66%-77% and a specificity of 93%. The distribution of active denervation may help to separate ALS from mimicking disorders at an early stage. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. [A multifocal form of cutaneous leishmaniasis caused by Leishmania infantum in an immunocompetent child treated with a short course of liposomal amphotericin B].

    Science.gov (United States)

    Taquin, H; Chiaverini, C; Marty, P; Lacour, J-P

    2016-10-01

    Cutaneous leishmaniasis (CL) is a parasitic infestation caused by various species of Leishmania protozoa transmitted by the bite of phlebotomine sand flies. Herein we report a case of multifocal CL due to Leishmania infantum in an immunocompetent child treated with liposomal amphotericin B. A 10-month-old baby was referred for multiple ulcerated nodules of the face and upper limbs present for 5 months and following travel to North Morocco. Histological and parasitological examinations resulted in a diagnosis of CL due to L. infantum. The child was treated with intravenous liposomal amphotericin B in accordance with the schedule for visceral leishmaniasis (10mg/kg over 2 days), and rapid improvement of the lesions was seen within 10 days. Clinical polymorphism of CL exists according to the infecting species. The multifocal presentation in our patient is very unusual for CL due to L. infantum in an immunocompetent child. To our knowledge, there have been no previous reports of successful use of parenteral liposomal amphotericin B for CL caused by L. infantum as described in our case. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. The Multirole of Liposomes in Therapy and Prevention of Infectious Diseases

    Directory of Open Access Journals (Sweden)

    Roberto Nisini

    2018-02-01

    Full Text Available Liposomes are closed bilayer structures spontaneously formed by hydrated phospholipids that are widely used as efficient delivery systems for drugs or antigens, due to their capability to encapsulate bioactive hydrophilic, amphipathic, and lipophilic molecules into inner water phase or within lipid leaflets. The efficacy of liposomes as drug or antigen carriers has been improved in the last years to ameliorate pharmacokinetics and capacity to release their cargo in selected target organs or cells. Moreover, different formulations and variations in liposome composition have been often proposed to include immunostimulatory molecules, ligands for specific receptors, or stimuli responsive compounds. Intriguingly, independent research has unveiled the capacity of several phospholipids to play critical roles as intracellular messengers in modulating both innate and adaptive immune responses through various mechanisms, including (i activation of different antimicrobial enzymatic pathways, (ii driving the fusion–fission events between endosomes with direct consequences to phagosome maturation and/or to antigen presentation pathway, and (iii modulation of the inflammatory response. These features can be exploited by including selected bioactive phospholipids in the bilayer scaffold of liposomes. This would represent an important step forward since drug or antigen carrying liposomes could be engineered to simultaneously activate different signal transduction pathways and target specific cells or tissues to induce antigen-specific T and/or B cell response. This lipid-based host-directed strategy can provide a focused antimicrobial innate and adaptive immune response against specific pathogens and offer a novel prophylactic or therapeutic option against chronic, recurrent, or drug-resistant infections.

  15. Linear arrangements of nano-scale ferromagnetic particles spontaneously formed in a copper-base Cu–Ni–Co alloy

    Science.gov (United States)

    Sakakura, Hibiki; Kim, Jun-Seop; Takeda, Mahoto

    2018-03-01

    We have investigated the influence of magnetic interactions on the microstructural evolution of nano-scale granular precipitates formed spontaneously in an annealed Cu-20at%Ni-5at%Co alloy and the associated changes of magnetic properties. The techniques used included transmission electron microscopy, superconducting quantum interference device (SQUID) magnetometry, magneto-thermogravimetry (MTG), and first-principles calculations based on the method of Koster–Korringa–Rostker with the coherent potential approximation. Our work has revealed that the nano-scale spherical and cubic precipitates which formed on annealing at 873 K and 973 K comprise mainly cobalt and nickel with a small amount of copper, and are arranged in the 〈1 0 0〉 direction of the copper matrix. The SQUID and MTG measurements suggest that magnetic properties such as coercivity and Curie temperature are closely correlated with the microstructure. The combination of results suggests that magnetic interactions between precipitates during annealing can explain consistently the observed precipitation phenomena.

  16. Slow fusion of liposomes composed of membrane-spanning lipids

    NARCIS (Netherlands)

    Elferink, MGL; vanBreemen, J; Konings, WN; Driessen, AJM; Wilschut, J; Elferink, Marieke G.L.

    1997-01-01

    The fusion characteristics of large unilamellar liposomes composed of bipolar tetraether lipids extracted from the thermophilic archaeon Sulfolobus acidocaldarius, was investigated. These lipids span the entire membrane and form single monolayer liposomes in aqueous media [Elferink, M.G.L., de Wit,

  17. Encapsulation of antitumor drug methotrexate in liposome vesicles

    International Nuclear Information System (INIS)

    Xu Bo; Sun Qixun; Zhang Nianbao; Xie Binghua; Zhang Jiong

    1990-01-01

    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 3 H-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%

  18. Rupture Pathway of Phosphatidylcholine Liposomes on Silicon Dioxide

    Directory of Open Access Journals (Sweden)

    Fredrik Höök

    2009-04-01

    Full Text Available We have investigated the pathway by which unilamellar POPC liposomes upon adsorption undergo rupture and form a supported lipid bilayer (SLB on a SiO2 surface. Biotinylated lipids were selectively incorporated in the outer monolayer of POPC liposomes to create liposomes with asymmetric lipid compositions in the outer and inner leaflets. The specific binding of neutravidin and anti-biotin to SLBs formed by liposome fusion, prior to and after equilibrated flip-flop between the upper and lower monolayers in the SLB, were then investigated. It was concluded that the lipids in the outer monolayer of the vesicle predominantly end up on the SLB side facing the SiO2 substrate, as demonstrated by having maximum 30-40% of lipids in the liposome outer monolayer orienting towards the bulk after forming the SLB.

  19. Human neural stem cell-derived cultures in three-dimensional substrates form spontaneously functional neuronal networks.

    Science.gov (United States)

    Smith, Imogen; Silveirinha, Vasco; Stein, Jason L; de la Torre-Ubieta, Luis; Farrimond, Jonathan A; Williamson, Elizabeth M; Whalley, Benjamin J

    2017-04-01

    Differentiated human neural stem cells were cultured in an inert three-dimensional (3D) scaffold and, unlike two-dimensional (2D) but otherwise comparable monolayer cultures, formed spontaneously active, functional neuronal networks that responded reproducibly and predictably to conventional pharmacological treatments to reveal functional, glutamatergic synapses. Immunocytochemical and electron microscopy analysis revealed a neuronal and glial population, where markers of neuronal maturity were observed in the former. Oligonucleotide microarray analysis revealed substantial differences in gene expression conferred by culturing in a 3D vs a 2D environment. Notable and numerous differences were seen in genes coding for neuronal function, the extracellular matrix and cytoskeleton. In addition to producing functional networks, differentiated human neural stem cells grown in inert scaffolds offer several significant advantages over conventional 2D monolayers. These advantages include cost savings and improved physiological relevance, which make them better suited for use in the pharmacological and toxicological assays required for development of stem cell-based treatments and the reduction of animal use in medical research. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  20. Liposome-encapsulated chemotherapy

    DEFF Research Database (Denmark)

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

    2018-01-01

    exist describing various liposomal drugs in healthy dogs. Also, some evidence for its use in veterinary cancer patients exists, especially in canine lymphoma, canine splenic hemangiosarcoma and feline soft tissue sarcoma, however, the results have not been overwhelming. Reasons for this may be related...... for liposomal therapy on an individual, non-histology-oriented, basis. Concurrently, new developments with active-release modified liposomes in experimental models and humans will likely be relevant for veterinary patients as well, and holds the potential to improve the therapeutic response. It, however, does...

  1. Tertiary Lymphoid Tissue Forms in Retinas of Mice with Spontaneous Autoimmune Uveitis and Has Consequences on Visual Function.

    Science.gov (United States)

    Kielczewski, Jennifer L; Horai, Reiko; Jittayasothorn, Yingyos; Chan, Chi-Chao; Caspi, Rachel R

    2016-02-01

    During chronic inflammation, tertiary lymphoid tissue (TLT) can form within an inflamed organ, including the CNS. However, little is known about TLT formation in the neuroretina. In a novel spontaneous autoimmune mouse model of uveitis (R161H), we identified well-organized lymphoid aggregates in the retina and examined them for TLT characteristics. Presence of immune cells, tissue-specific markers, and gene expression patterns typically associated with germinal centers and T follicular helper cells were examined using immunohistochemistry and gene analysis of laser capture microdissected retina. Our data revealed the retinal lymphoid structures contained CD4(+) T cells and B cells in well-defined zonal areas that expressed classic germinal center markers, peanut lectin (agglutinin) and GL-7. Gene expression analysis showed upregulation of T follicular helper cell markers, most notably CXCR5 and its ligand CXCL13, and immunohistochemical analysis confirmed CXCR5 expression, typically associated with CD4(+) T follicular helper cells. Highly organized stromal cell networks, a hallmark of organized lymphoid tissue, were also present. Positive staining for phospho-Zap70 in retina-specific T cells indicated CD4(+) T cells were being activated within these lymphoid structures. CD138(+)/B220(+) plasma cells were detected, suggesting the retinal lymphoid aggregates give rise to functional germinal centers, which produce Abs. Interestingly, eyes with lymphoid aggregates exhibited lower inflammatory scores by fundus examination and a slower initial rate of loss of visual function by electroretinography, compared with eyes without these structures. Our findings suggest that the lymphoid aggregates in the retina of R161H mice represent organized TLT, which impact the course of chronic uveitis.

  2. Solid state solvation effect and reduced amplified spontaneous emission threshold value of glass forming DCM derivative in PMMA films

    Energy Technology Data Exchange (ETDEWEB)

    Vembris, Aivars, E-mail: aivars.vembris@cfi.lu.lv [Institute of Solid State Physics, University of Latvia, 8 Kengaraga Street, Riga LV 1063 (Latvia); Zarins, Elmars; Kokars, Valdis [Institute of Applied Chemistry, Riga Technical University, 14/24 Azenes Street, Riga LV 1048 (Latvia)

    2015-02-15

    Molecule crystallization is one of the limitations for obtaining high-gain organic laser systems. One of the examples is well known red laser dye 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran (DCM). The lowest threshold value of amplified spontaneous emission was achieved by doping 2 wt% of DCM molecule in tris-(8-hydroxy quinoline) aluminum (Alq{sub 3}) matrix. Further increase of the DCM dye concentration makes the system less efficient as its threshold value increases. It is due to large intermolecular interaction, which induces photoluminescence quenching. Compounds with reduced intermolecular interaction could be prospective in organic laser systems due to higher possible doping. In this work photoluminescence and amplified spontaneous emission properties of modified DCM molecule in poly(methyl methacrylate) (PMMA) matrix were investigated. Bulky trityloxyethyl groups were attached to the donor part of DCM. These groups increase intermolecular distance wherewith reduce photoluminescence quenching. More than one order of magnitude lower excitation threshold energy of the amplified spontaneous emission was achieved in doped polymer films with investigated compound in comparison to doped polymer with DCM. It means that the investigated compound is more perspective as a laser material compared to the previously studied. In addition, amplified spontaneous emission maximum could be tuned within 15 nm by changing concentration from 0.1 wt% to 10 wt% DWK-1 in PMMA matrix due to solid state solvation effect. - Highlights: • Bulky groups attached to DCM dye reduce photoluminescence quenching. • Amplified spontaneous emission is in red spectral region. • Amplified spontaneous emission spectra were tuned by 15 nm. • Amplified spontaneous emission threshold value was reduced by one order of magnitude.

  3. Fluorescence and amplified spontaneous emission of glass forming compounds containing styryl-4H-pyran-4-ylidene fragment

    Energy Technology Data Exchange (ETDEWEB)

    Vembris, Aivars, E-mail: aivars.vembris@cfi.lu.lv [Institute of Solid State Physics, University of Latvia, 8 Kengaraga Street, Riga LV-1063 (Latvia); Muzikante, Inta [Institute of Solid State Physics, University of Latvia, 8 Kengaraga Street, Riga LV-1063 (Latvia); Karpicz, Renata; Sliauzys, Gytis [Institute of Physics, Center for Physical Sciences and Technology, A. Gostauto 11, LT-01108 Vilnius (Lithuania); Miasojedovas, Arunas; Jursenas, Saulius [Institute of Applied Research, Vilnius University, Sauletekio 9-III, LT-10222 Vilnius (Lithuania); Gulbinas, Vidmantas [Institute of Physics, Center for Physical Sciences and Technology, A. Gostauto 11, LT-01108 Vilnius (Lithuania)

    2012-09-15

    Potential of glassy films of newly synthesised low molecular weight organic molecules for light amplification and lasing applications has been investigated by analysing fluorescence, transient differential absorption and amplified spontaneous emission properties. These non-symmetric and symmetric molecules contain styryl-4H-pyran-4-ylidene fragment with three different electron acceptor groups: dicyanomethylene, barbituric acid, indene-1,3-dione. Fluorescence quantum yields of the investigated compounds in solutions are between 0.32 and 0.54, while they drop down by an order of magnitude in thin solid films. Incorporation of bulky side groups reduced excitonic interactions enabling manifestation of amplified spontaneous emission in the neat films of the investigated derivatives. - Highlights: Black-Right-Pointing-Pointer Bulky substituents attached to DCM dye enable formation of neat glassy films. Black-Right-Pointing-Pointer Investigated dyes show amplified spontaneous emission in neat films. Black-Right-Pointing-Pointer Two electron donor groups negatively influence light amplification.

  4. 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.

  5. Liposomes for Use in Gene Delivery

    Directory of Open Access Journals (Sweden)

    Daniel A. Balazs

    2011-01-01

    Full Text Available Liposomes have a wide array of uses that have been continuously expanded and improved upon since first being observed to self-assemble into vesicular structures. These arrangements can be found in many shapes and sizes depending on lipid composition. Liposomes are often used to deliver a molecular cargo such as DNA for therapeutic benefit. The lipids used to form such lipoplexes can be cationic, anionic, neutral, or a mixture thereof. Herein physical packing parameters and specific lipids used for gene delivery will be discussed, with lipids classified according to overall charge.

  6. Boron-Containing Compounds for Liposome-Mediated Tumor Localization and Application to Neutron Capture Therapy

    International Nuclear Information System (INIS)

    Hawthorne, M. Frederick

    2005-01-01

    unimolecular nanoparticles presenting several advantages: tunable size through functionalization and branching, spherical shape due to the icosahedral B122 core, promising water solubility resulting from degradation of all pendant closo-carborane groups to their hydrophilic nido anion substituents, and efficient boron delivery owing to the presence of 120 boron atoms which gives rise to a boron content as high as 40% by weight. Keeping the new objective in mind, we have focused on the design, synthesis and evaluation of new and very boron-rich closomer species. Additionally, progress has also been made toward the evaluation of a newly synthesized boron-rich lipid as a substitute for DSPC in bilayer construction, and the boron content of the resulting liposomes has been greatly enhanced. Related research involving the synthesis and self-assembly of carborane-containing amphiphiles has been systematically studied. Combined hydrophobic and hydrophilic properties of the single-chain amphiphiles allow their spontaneous self-assembly to form rods under a variety of variable conditions, such as concentration in the bilayer, carborane cage structure, chain-length, counterion identity, solvents, methods of preparation, and the ionic charge. On the other hand, the number of attached chains affects the self-assembly process. Particles having totally different shapes have been observed for dual-chain amphiphiles.

  7. Boron-Containing Compounds for Liposome-Mediated Tumor Localization and Application to Neutron Capture Therapy

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-04-07

    amphiphilic unimolecular nanoparticles presenting several advantages: tunable size through functionalization and branching, spherical shape due to the icosahedral B122 core, promising water solubility resulting from degradation of all pendant closo-carborane groups to their hydrophilic nido anion substituents, and efficient boron delivery owing to the presence of 120 boron atoms which gives rise to a boron content as high as 40% by weight. Keeping the new objective in mind, we have focused on the design, synthesis and evaluation of new and very boron-rich closomer species. Additionally, progress has also been made toward the evaluation of a newly synthesized boron-rich lipid as a substitute for DSPC in bilayer construction, and the boron content of the resulting liposomes has been greatly enhanced. Related research involving the synthesis and self-assembly of carborane-containing amphiphiles has been systematically studied. Combined hydrophobic and hydrophilic properties of the single-chain amphiphiles allow their spontaneous self-assembly to form rods under a variety of variable conditions, such as concentration in the bilayer, carborane cage structure, chain-length, counterion identity, solvents, methods of preparation, and the ionic charge. On the other hand, the number of attached chains affects the self-assembly process. Particles having totally different shapes have been observed for dual-chain amphiphiles.

  8. Clinical characteristics of post-neurosurgical Klebsiella pneumoniae meningitis in adults and a clinical comparison to the spontaneous form in a Taiwanese population.

    Science.gov (United States)

    Chang, Wen-Neng; Lu, Chen-Hsien; Huang, Chi-Ren; Chuang, Yao-Chung; Tsai, Nai-Wen; Chang, Chiung-Chih; Chen, Shu-Fang; Wang, Hung-Chen; Yang, Tzu-Ming; Hsieh, Mei-Jen; Chien, Chun-Chih

    2010-03-01

    A total of 46 patients (nine post-neurosurgical, 37 spontaneous) with adult bacterial meningitis (ABM) caused by Klebsiellapneumoniae infection were included in this study. The nine patients in the post-neurosurgical K. pneumoniae ABM group (seven male, two female) had a mean age of 48.9 years. Two patients in this group also had diabetes mellitus (DM) and one had liver disease. The most common presentation of patients in post-neurosurgical K. pneumoniae ABM group was fever (nine patients), followed by altered consciousness (seven patients) and hydrocephalus (six patients). With medical and/or surgical treatment, a mortality of 22.2% (2/9) occurred. Compared to patients who had spontaneous K. pneumoniae ABM, those with the post-neurosurgical form had a lower incidence of community-acquired infection, seizure and DM, but had a higher incidence of leukocytosis, hydrocephalus, cerebrospinal fluid leak and bacterial strains with extended-spectrum beta-lactamase. Univariate analysis found these clinical differences to be statistically significant, however they were not significant on multivariate analysis. This study reveals that there are clinical differences between the post-neurosurgical and spontaneous presentations of K. pneumoniae ABM. Copyright 2009 Elsevier Ltd. All rights reserved.

  9. Stabilization of liophilized liposomal products

    Directory of Open Access Journals (Sweden)

    2001-08-01

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

  10. Films of Agarose Enable Rapid Formation of Giant Liposomes in Solutions of Physiologic Ionic Strength

    OpenAIRE

    Horger, Kim S.; Estes, Daniel J.; Capone, Ricardo; Mayer, Michael

    2009-01-01

    This paper describes a method to form giant liposomes in solutions of physiologic ionic strength, such as phosphate buffered saline (PBS) or 150 mM KCl. Formation of these cell-sized liposomes proceeded from hybrid films of partially dried agarose and lipids. Hydrating the films of agarose and lipids in aqueous salt solutions resulted in swelling and partial dissolution of the hybrid films and in concomitant rapid formation of giant liposomes in high yield. This method did not require the pre...

  11. A generic 89Zr labeling method to quantify the in vivo pharmacokinetics of liposomal nanoparticles with positron emission tomography.

    Science.gov (United States)

    Li, Nan; Yu, Zilin; Pham, Truc Thuy; Blower, Philip J; Yan, Ran

    2017-01-01

    Liposomal nanoparticles are versatile drug delivery vehicles that show great promise in cancer therapy. In an effort to quantitatively measure their in vivo pharmacokinetics, we developed a highly efficient 89 Zr liposome-labeling method based on a rapid ligand exchange reaction between the membrane-permeable 89 Zr(8-hydroxyquinolinate) 4 complex and the hydrophilic liposomal cavity-encapsulated deferoxamine (DFO). This novel 89 Zr-labeling strategy allowed us to prepare radiolabeled forms of a folic acid (FA)-decorated active targeting 89 Zr-FA-DFO-liposome, a thermosensitive 89 Zr-DFO-liposome, and a renal avid 89 Zr-PEG-DFO-liposome at room temperature with near-quantitative isolated radiochemical yields of 98%±1% (n=6), 98%±2% (n=5), and 97%±1% (n=3), respectively. These 89 Zr-labeled liposomal nanoparticles showed remarkable stability in phosphate-buffered saline and serum at 37°C without leakage of radioactivity for 48 h. The uptake of 89 Zr-FA-DFO-liposome by the folate receptor-overexpressing KB cells was almost 15-fold higher than the 89 Zr-DFO-liposome in vitro. Positron emission tomography imaging and ex vivo biodistribution studies enabled us to observe the heterogeneous distribution of the 89 Zr-FA-DFO-liposome and 89 Zr-DFO-liposome in the KB tumor xenografts, the extensive kidney accumulation of the 89 Zr-FA-DFO-liposome and 89 Zr-PEG-DFO-liposome, and the different metabolic fate of the free and liposome-encapsulated 89 Zr-DFO. It also unveiled the poor resistance of all three liposomes against endothelial uptake resulting in their catabolism and high uptake of free 89 Zr in the skeleton. Thus, this technically simple 89 Zr-labeling method would find widespread use to guide the development and clinical applications of novel liposomal nanomedicines.

  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. Atmospheric-pressure guided streamers for liposomal membrane disruption

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  14. Attenuation of dermal toxicity of doxorubicin by liposome encapsulation.

    Science.gov (United States)

    Forssen, E A; Tökes, Z A

    1983-05-01

    The severe tissue damage which occurs when doxorubicin (Dxn) is extravasated during infusion has been attenuated by encapsulating the drug in anionic liposomes. Mice were injected intradermally with either 0.05 or 0.10 mg of Dxn in the free or liposome-entrapped form. At both dose levels, the animals receiving free drug developed dermal lesions at a higher frequency and of a greater severity than did those animals receiving Dxn-liposomes. Determination of tissue-associated fluorescence indicated that free Dxn was removed from the area of the dermal injection more rapidly than was the liposome-entrapped drug. The data suggest that the dermal toxicity of Dxn may be determined more by its mode of disposition than by the absolute amount of drug in tissue. Similar observation was made earlier for the Dxn-induced chronic cardiotoxicity.

  15. High-Efficiency Fullerene Solar Cells Enabled by a Spontaneously Formed Mesostructured CuSCN-Nanowire Heterointerface

    KAUST Repository

    Sit, Wai-Yu

    2018-02-02

    Fullerenes and their derivatives are widely used as electron acceptors in bulk-heterojunction organic solar cells as they combine high electron mobility with good solubility and miscibility with relevant semiconducting polymers. However, studies on the use of fullerenes as the sole photogeneration and charge-carrier material are scarce. Here, a new type of solution-processed small-molecule solar cell based on the two most commonly used methanofullerenes, namely [6,6]-phenyl-C61-butyric acid methyl ester (PC60BM) and [6,6]-phenyl-C71-butyric acid methyl ester (PC70BM), as the light absorbing materials, is reported. First, it is shown that both fullerene derivatives exhibit excellent ambipolar charge transport with balanced hole and electron mobilities. When the two derivatives are spin-coated over the wide bandgap p-type semiconductor copper (I) thiocyanate (CuSCN), cells with power conversion efficiency (PCE) of ≈1%, are obtained. Blending the CuSCN with PC70BM is shown to increase the performance further yielding cells with an open-circuit voltage of ≈0.93 V and a PCE of 5.4%. Microstructural analysis reveals that the key to this success is the spontaneous formation of a unique mesostructured p–n-like heterointerface between CuSCN and PC70BM. The findings pave the way to an exciting new class of single photoactive material based solar cells.

  16. Successful co-encapsulation of benzoyl peroxide and chloramphenicol in liposomes by a novel manufacturing method - dual asymmetric centrifugation.

    Science.gov (United States)

    Ingebrigtsen, Sveinung G; Škalko-Basnet, Nataša; de Albuquerque Cavalcanti Jacobsen, Cristiane; Holsæter, Ann Mari

    2017-01-15

    Encapsulation of more than one active pharmaceutical ingredient into nanocarriers such as liposomes is an attractive approach to achieve a synergic drug effect and less complicated dosing schedules in multi-drug treatment regimes. Liposomal drug delivery in acne treatment may improve drug efficiency by targeted delivery to pilosebaceous units, reduce adverse effects and improve patient compliance. We therefore aimed to co-encapsulate benzoyl peroxide (BPO) and chloramphenicol (CAM) into liposomes using the novel liposome processing method - dual asymmetric centrifugation (DAC). Liposomes were formed from soybean lecithin, propylene glycol and distilled water (2:1:2w/v/v ratio), forming a viscous liposome dispersion. Liposomes containing both drugs (BPO-CAM-Lip), single drug (BPO-Lip and CAM-Lip), and empty liposomes were prepared. Drug entrapment of BPO and CAM was determined by a newly developed HPLC method for simultaneous detection and quantification of both drugs. Encapsulation of around 50% for BPO and 60% for CAM respectively was obtained in both single-drug encapsulated formulations (BPO-Lip and CAM-Lip) and co-encapsulated formulations (BPO-CAM-Lip). Liposome sizes were comparable for all liposome formulations, ranging from 130 to 150nm mean diameter, with a polydispersity index <0.2 for all formulations. CAM exhibited a sustained release from all liposomal formulations, whereas BPO appeared retained within the liposomes. BPO retention could be attributed to its poor solubility. However, HaCaT cell toxicity was found dependent on BPO released from the liposomes. In the higher concentration range (4%v/v), liposomal formulations were less cytotoxic than the corresponding drug solutions used as reference. We have demonstrated that DAC is a fast, easy, suitable method for encapsulation of more than one drug within the same liposomes. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Boronated liposome development and evaluation

    International Nuclear Information System (INIS)

    Hawthorne, M.F.

    1995-01-01

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

  18. Preformulation Studies of a Liposomal Formulation Containing Sirolimus for the Treatment of Dry Eye Disease.

    Science.gov (United States)

    Linares-Alba, Mónica Anayántzin; Gómez-Guajardo, Magda Berenice; Fonzar, Joice Furtado; Brooks, Dennis E; García-Sánchez, Gustavo Adolfo; Bernad-Bernad, Maria Josefa

    2016-01-01

    The aim of this study was to develop and characterize a liposomal product containing sirolimus to be administered subconjunctivally for the treatment of nonresponsive keratoconjunctivitis sicca (KCS) or dry eye. Formulations were prepared using an ethanol injection method and an adaptation of the heating method in pursuance of the most suitable methodology for future industrial production. Liposomes were loaded with either a high dose of 1 mg/mL of sirolimus or a less toxic dose of 0.4 mg/mL. The effects of critical process and formulation parameters were investigated. Liposomes were characterized in terms of size, zeta potential, polydispersity, differential scanning calorimetry, morphology, entrapment efficiency, phospholipid content, thermal stability, and sterility. The formulation was evaluated clinically in dogs with spontaneous KCS. Sterile liposomal dispersions with sizes ranging from 140 to 211 nm, were successfully obtained. High entrapment efficiency of 93%-98% was achieved. The heating method allowed an easier production of liposomes with high entrapment efficiency, to significantly shorten production time and the elimination of the use of alcohol. The poor stability of the obtained liposomes in aqueous dispersion made the inclusion of a lyophilization step necessary to the manufacturing process. In vivo testing of the liposomal sirolimus formulations in the spontaneous KCS dog model have produced promising results, particularly with a sirolimus dose of 1 mg/mL, indicating the need for further development and study of proposed formulations in the treatment of canine KCS. Clinical improvement in tear production in dogs with spontaneous KCS treated with the 1 mg/mL dose product was observed. The heating method allowed easier production of high entrapment efficiency liposomes to significantly shorten production time and the elimination of the use of alcohol. Tear production was increased in dogs administered with the formulation.

  19. Temoporfin-loaded liposomes

    DEFF Research Database (Denmark)

    Kuntsche, Judith; Freisleben, Ines; Steiniger, Frank

    2010-01-01

    some problems associated with the commercial formulation Foscan where the drug is dissolved in a mixture of water-free ethanol and propylene glycol. The present study focuses on the physicochemical characterization of different liposome formulations with special emphasis on the influence of drug...... 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....

  20. Recent advances in liposomal dry powder formulations: preparation and evaluation.

    Science.gov (United States)

    Misra, Ambikanandan; Jinturkar, Kaustubh; Patel, Deepa; Lalani, Jigar; Chougule, Mahavir

    2009-01-01

    Liposomal drug dry powder formulations have shown many promising features for pulmonary drug administration, such as selective localization of drug within the lung, controlled drug release, reduced local and systemic toxicities, propellant-free nature, patient compliance, high dose carrying capacity, stability and patent protection. Critical review of the recent developments will provide a balanced view on benefits of liposomal encapsulation while developing dry powder formulations and will help researchers to update themselves and focus their research in more relevant areas. In liposomal dry powder formulations (LDPF), drug encapsulated liposomes are homogenized, dispersed into the carrier and converted into dry powder form by using freeze drying, spray drying and spray freeze drying. Alternatively, LDPF can also be formulated by supercritical fluid technologies. On inhalation with a suitable inhalation device, drug encapsulated liposomes get rehydrated in the lung and release the drug over a period of time. The prepared LDPF are evaluated in vitro and in vivo for lung deposition behavior and drug disposition in the lung using a suitable inhaler device. The most commonly used liposomes are composed of lung surfactants and synthetic lipids. Delivery of anticancer agents for lung cancer, corticosteroids for asthma, immunosuppressants for avoiding lung transplantation rejection, antifungal drugs for lung fungal infections, antibiotics for local pulmonary infections and cystic fibrosis and opioid analgesics for pain management using liposome technology are a few examples. Many liposomal formulations have reached the stage of clinical trials for the treatment of pulmonary distress, cystic fibrosis, lung fungal infection and lung cancer. These formulations have given very promising results in both in vitro and in vivo studies. However, modifications to new therapies for respiratory diseases and systemic delivery will provide new challenges in conducting well

  1. 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.

  2. Aberrant chlamydial developmental forms in the gastrointestinal tract of pigs spontaneously and experimentally infected with Chlamydia suis.

    Science.gov (United States)

    Pospischil, Andreas; Borel, Nicole; Chowdhury, Emdad H; Guscetti, Franco

    2009-03-16

    The phenomenon of persistence is well known from in vitro studies, where it is associated with the production of aberrant bodies, but its occurrence in vivo is less well documented. The objective of this study was to search for aberrant bodies in intestinal tissues from pigs, describe their ultrastructure, and investigate the suitability of immunohistochemical staining for chlamydial heat shock protein 60 (cHSP60) to detect such forms. Intestinal tissues derived from pigs naturally and experimentally infected with Chlamydia (C.) suis were examined by immunohistochemistry, transmission electron microscopy and immunogold electron microscopy. The chlamydial species involved in the natural infection were determined using an Array Tube Microarray to C. suis and Chlamydophila abortus. Ultrastructurally, aberrant bodies were detected in the gut of both naturally and experimentally infected pigs. Immunogold electron microscopy showed that the aberrant bodies were labeled less strongly than the normal forms by antibodies against LPS and cHSP60 respectively. It was concluded that aberrant bodies occur in vivo in pigs and that the gnotobiotic pig model might be suitable for the study of chlamydial persistence in vivo. The antibody against cHSP60 does not appear to be suitable to specifically detect such forms.

  3. Liposome: classification, preparation, and applications

    Science.gov (United States)

    Akbarzadeh, Abolfazl; Rezaei-Sadabady, Rogaie; Davaran, Soodabeh; Joo, Sang Woo; Zarghami, Nosratollah; Hanifehpour, Younes; Samiei, Mohammad; Kouhi, Mohammad; Nejati-Koshki, Kazem

    2013-02-01

    Liposomes, sphere-shaped vesicles consisting of one or more phospholipid bilayers, were first described in the mid-60s. Today, they are a very useful reproduction, reagent, and tool in various scientific disciplines, including mathematics and theoretical physics, biophysics, chemistry, colloid science, biochemistry, and biology. Since then, liposomes have made their way to the market. Among several talented new drug delivery systems, liposomes characterize an advanced technology to deliver active molecules to the site of action, and at present, several formulations are in clinical use. Research on liposome technology has progressed from conventional vesicles 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. This paper summarizes exclusively scalable techniques and focuses on strengths, respectively, limitations in respect to industrial applicability and regulatory requirements concerning liposomal drug formulations based on FDA and EMEA documents.

  4. Encapsulation of a Lactic Acid Bacteria Cell-Free Extract in Liposomes and Use in Cheddar Cheese Ripening

    Science.gov (United States)

    Nongonierma, Alice Beebyaanda; Abrlova, Magdalena; Kilcawley, Kieran Noel

    2013-01-01

    A concentrated form of cell free extract (CFE) derived from attenuated Lactococcus lactis supsb. lactis 303 CFE was encapsulated in liposomes prepared from two different proliposome preparations (Prolipo Duo and Prolipo S) using microfluidization. Entrapment efficiencies of 19.7 % (Prolipo S) and 14.0 % (Prolipo Duo) were achieved and the preparations mixed in the ratio 4 (Prolipo Duo):1 (Prolipo S). Cheddar cheese trials were undertaken evaluating the performance of CFE entrapped in liposomes, empty liposomes and free CFE in comparison to a control cheese without any CFE or liposomes. Identical volumes of liposome and amounts of CFE were used in triplicate trials. The inclusion of liposomes did not adversely impact on cheese composition water activity, or microbiology. Entrapment of CFE in liposomes reduced loss of CFE to the whey. No significant differences were evident in proteolysis or expressed PepX activity during ripening in comparison to the cheeses containing free CFE, empty liposomes or the control, as the liposomes did not degrade during ripening. This result highlights the potential of liposomes to minimize losses of encapsulated enzymes into the whey during cheese production but also highlights the need to optimize the hydrophobicity, zeta potential, size and composition of the liposomes to maximize their use as vectors for enzyme addition in cheese to augment ripening. PMID:28239101

  5. Liposome based radiosensitizer cancer therapy

    DEFF Research Database (Denmark)

    Pourhassan, Houman

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

  6. Propulsion of liposomes using bacterial motors

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  7. Efficacy of neutral and negatively charged liposome-loaded gentamicin on planktonic bacteria and biofilm communities.

    Science.gov (United States)

    Alhariri, Moayad; Majrashi, Majed A; Bahkali, Ali H; Almajed, Faisal S; Azghani, Ali O; Khiyami, Mohammad A; Alyamani, Essam J; Aljohani, Sameera M; Halwani, Majed A

    2017-01-01

    We investigated the efficacy of liposomal gentamicin formulations of different surface charges against Pseudomonas aeruginosa and Klebsiella oxytoca . The liposomal gentamicin formulations were prepared by the dehydration-rehydration method, and their sizes and zeta potential were measured. Gentamicin encapsulation efficiency inside the liposomal formulations was determined by microbiologic assay, and stability of the formulations in biologic fluid was evaluated for a period of 48 h. The minimum inhibitory concentration and the minimum bactericidal concentration were determined, and the in vitro time kill studies of the free form of gentamicin and liposomal gentamicin formulations were performed. The activities of liposomal gentamicin in preventing and reducing biofilm-forming P. aeruginosa and K. oxytoca were compared to those of free antibiotic. The sizes of the liposomal formulations ranged from 625 to 806.6 nm in diameter, with the zeta potential ranging from -0.22 to -31.7 mV. Gentamicin encapsulation efficiency inside the liposomal formulation ranged from 1.8% to 43.6%. The liposomes retained >60% of their gentamicin content during the 48 h time period. The minimum inhibitory concentration of neutral formulation was lower than that of free gentamicin (0.25 versus 1 mg/L for P. aeruginosa and 0.5 versus 1 mg/L for K. oxytoca ). The negatively charged formulation exhibited the same bacteriostatic concentration as that of free gentamicin. The minimum bactericidal concentration of neutral liposomes on planktonic bacterial culture was twofold lower than that of free gentamicin, whereas the negatively charged formulations were comparable to free gentamicin. The killing time curve values for the neutral negatively charged formulation against planktonic P. aeruginosa and K. oxytoca were better than those of free gentamicin. Furthermore, liposomal formulations prevent the biofilm-formation ability of these strains better than free gentamicin. In summary, liposomal

  8. Trifluralin liposomal formulations active against Leishmania donovani infections.

    Science.gov (United States)

    Carvalheiro, Manuela; Jorge, João; Eleutério, Carla; Pinhal, Ana F; Sousa, Ana C; Morais, José G; Cruz, M Eugénia M

    2009-02-01

    The purpose of this study was to increase the therapeutic index of the antiparasitic drug, trifluralin (TFL), to allow its parenteral administration without the need of toxic solvents. This was achieved by incorporating TFL in liposomes with high loading capacity. These formulations were stable in freeze-dried form during at least one year and in frozen form during at least three months. Therapeutic activity, assessed on a visceral model of infection, showed that TFL liposomes reduced the number of parasites by up to one third or one half as compared to negative control and to free TFL, respectively.

  9. Influence of Quil A on liposomal membranes.

    Science.gov (United States)

    Paepenmüller, T; Müller-Goymann, C C

    2014-11-20

    Quil A is the purified saponin fraction extracted from the bark of Quillaja saponaria Molina. Besides its utilisation as a surfactant, it is commonly used in a pseudo-ternary system with cholesterol and phospholipid to form colloidal structures known as ISCOMs (immunostimulating complexes). Their appropriateness as immune stimulating drug carriers has been widely demonstrated, albeit the evaluation of physico-chemical properties of the ISCOM matrix still draws a heterogeneous picture. The aim of our study was to elucidate the effects of Quil A on liposomal phosphatidylcholine/cholesterol dispersions as this interaction is regarded as the major step for the formation of the ISCOM matrix. Transmission electron microscopy was applied to observe structural changes of liposomal dispersions upon addition of Quil A. A formation of ISCOM matrices readily out of the liposomal membrane was proven. The entrapment efficiency (EE) of Arsenazo III as well as differential thermal analysis (DSC) also demonstrated an interaction between the components above a critical concentration of Quil A. To further clarify the effects of interaction, Langmuir trough experiments of insoluble monolayers of both cholesterol and PC and their interaction with Quil A were performed. Measurable effects even below the critical concentration of Quil A (derived from DSC and EE) were shown. Cholesterol had a major impact on the formation and stabilisation of the ISCOM matrix. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Biological activity of liposomal vanillin.

    Science.gov (United States)

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

    2013-06-01

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

  11. Advances in Tumor Targeted Liposomes.

    Science.gov (United States)

    Jain, A; Jain, S K

    2018-04-15

    Cancer remains a deadly disease for effective treatment. Although anomalous tumor microenvironment is now widely exploited for targeted chemotherapy, safe and efficacious drug delivery to tumor cells is not still warranted. Liposomes are promising biodegradable and biocompatible nanocarriers having potential amenability for surface and internal modifications, and extraordinary capability to carry both hydrophilic as well as hydrophobhic drugs. Meticulous fabrication of liposomes with tumor selective ligand(s) and PEGylation reduces immunogenicity and increase target-specificity. This chapter focuses on critical developmental aspects of liposomes to target cancer cells exploiting Enhanced Permeability and Retention (EPR) effect and tumor-selective ligands such as folate, transferrin, peptides etc. Moreover, stimuli-responsive smart liposomes (triggers: pH, temperature, enzymes, magnetic field, ultrasound, and redox potential etc.) are also investigated for enhancement of drug delivery to tumors. This review summarizes advances in tumor-targeted liposomes via various means of targeting. This knowledgeable assemblage of advances in liposomal approaches will render new insights to formulators and budding scientists to design cancer targeted liposomes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. A novel liposome-encapsulated hemoglobin/silica nanoparticle as an oxygen carrier.

    Science.gov (United States)

    Liu, Mingxian; Gan, Lihua; Chen, Liuhua; Zhu, Dazhang; Xu, Zijie; Hao, Zhixian; Chen, Longwu

    2012-05-10

    A novel liposome-encapsulated hemoglobin/silica nanoparticle (LEHSN) was fabricated by a water-in-oil-in-water (W/O/W) double emulsion approach. Bovine hemoglobin (Hb) was first adsorbed onto the surfaces of silica nanoparticles (SNs), and then the complex of Hb/SNs was encapsulated by liposome to form LEHSN which has a core-shell supramolecular structure. On the one hand, liposomes built a cell membrane-like environment for the controlled release of Hb. On the other hand, SNs which act as rigid core provide a supported framework for lecithin membrane, and enhance the stability of liposomes. In comparison with liposome-encapsulated Hb (LEH), LEHSN shows substantially enhanced stability and improved release property of Hb in vitro. This study highlights the potential of the novel LEHSN as an oxygen carrier for pharmaceutical applications. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Role of liposome in treatment of overactive bladder and interstitial cystitis

    Directory of Open Access Journals (Sweden)

    Shih-Ya Hung

    2015-03-01

    Full Text Available Intravesical (local therapy of agents has been effective in delaying or preventing recurrence of superficial bladder cancer. This route of drug administration has also shown tremendous promise in the treatment of interstitial cystitis/painful bladder syndrome (IC/PBS and overactive bladder without systemic side effects. Liposomes are lipid vesicles composed of phospholipid bilayers surrounding an aqueous core. They can incorporate drug molecules, both hydrophilic and hydrophobic, and show greater uptake into cells via endocytosis. Intravesical liposomes have therapeutic effects on IC/PBS patients, mainly because of their ability to form a protective lipid film on the urothelial surface. Recent studies have shown the sustained efficacy and safety of intravesical instillation of botulinum toxin formulated with liposomes (lipo-BoNT for the treatment of refractory overactive bladder This review considers the current status of intravesical liposomes or liposomal mediated drug delivery for the treatment of IC/PBS and overactive bladder.

  14. The effect of liposomes on skin barrier structure.

    Science.gov (United States)

    Coderch, L; de Pera, M; Perez-Cullell, N; Estelrich, J; de la Maza, A; Parra, J L

    1999-01-01

    The present work deals with the 'in vivo' stripping technique to evaluate the percutaneous absorption of sodium fluorescein (NaFl) vehiculized in two different liposome preparations formed by phosphatidylcholine (PC) and lipids mimicking the stratum corneum (SC; ceramides, cholesterol, palmitic acid and cholesteryl sulphate), respectively. Furthermore, the possible effect of these vesicles on the SC lipid alkyl chain conformational order were evaluated at different depths of SC by non-invasive biophysical techniques: Corneometer, Tewameter and especially ATR-FTIR. The results of NaFl percutaneous absorption indicate the highest penetration in the case of incorporation in PC liposomes, which could be related to the increase in SC lipid disorder detected by ATR-FTIR, i.e. a decrease in skin barrier function. On the other hand, SC lipid liposomes have been shown to have a higher affinity for SC owing to the high amount of NaFl found in this layer, suggesting a greater reservoir capacity of SC when similar lipid composition formulation is applied. A lipid order increase is observed by infrared spectroscopy, when these types of liposomes are topically applied, resulting in a strong barrier effect. These results could be useful in designing specific liposomal topical applications.

  15. Ethosomes and liposomes as topical vehicles for azelaic acid: a preformulation study.

    Science.gov (United States)

    Esposito, Elisabetta; Menegatti, Enea; Cortesi, Rita

    2004-01-01

    The basic properties and the in vitro release rate kinetics of azelaic acid (AA), alternatively vehiculated in different phospholipid-based vesicles such as ethosomes or liposomes, were investigated. Ethosomes were produced by a simple method based on addition of an aqueous phase to an ethanol solution (comprised between 20\\% and 45%, v/v) of soy phosphatidyl choline (5%, w/w) and AA (0.2%, w/w) under mechanical stirring. Liposomes were obtained by the same composition in the absence of ethanol with the reverse-phase evaporation method. Vesicle size was measured by photon correlation spectroscopy (PCS), evidencing smaller mean diameters and narrower dimensional distributions in the case of ethosomes with respect to liposomes. In order to obtain homogeneously sized vesicles, both ethosomal and liposomal dispersions were extruded through polycarbonate membranes with pores of calibrated diameter (400 nm and 200 nm). Vesicle morphology was characterized by freeze-fracture scanning electron microscopy (SEM) showing the presence of unilamellar vesicles both in liposome- and in ethosome-based dispersions. Free energy measurements of the vesicle bilayers were conducted by differential scanning calorimetry (DSC). AA diffusion from ethosomal or liposomal dispersions and from ethosomes and liposomes incorporated in a viscous gel was investigated by a Franz cell assembled with synthetic membranes. The release rate was more rapid from ethosomal systems than from liposomal systems. In particular, ethosomes produced by the highest ethanol concentration released AA more rapidly, and the same trend was found using viscous forms.

  16. Preparation, characterization and in vitro antimicrobial activity of liposomal ceftazidime and cefepime against Pseudomonas aeruginosa strains

    Science.gov (United States)

    Torres, Ieda Maria Sapateiro; Bento, Etiene Barbosa; Almeida, Larissa da Cunha; de Sá, Luisa Zaiden Carvalho Martins; Lima, Eliana Martins

    2012-01-01

    Pseudomonas aeruginosa is an opportunistic microorganism with the ability to respond to a wide variety of environmental changes, exhibiting a high intrinsic resistance to a number of antimicrobial agents. This low susceptibility to antimicrobial substances is primarily due to the low permeability of its outer membrane, efflux mechanisms and the synthesis of enzymes that promote the degradation of these drugs. Cephalosporins, particularty ceftazidime and cefepime are effective against P. aeruginosa, however, its increasing resistance has limited the usage of these antibiotics. Encapsulating antimicrobial drugs into unilamellar liposomes is an approach that has been investigated in order to overcome microorganism resistance. In this study, antimicrobial activity of liposomal ceftazidime and cefepime against P. aeruginosa ATCC 27853 and P. aeruginosa SPM-1 was compared to that of the free drugs. Liposomal characterization included diameter, encapsulation efficiency and stability. Minimum Inhibitory Concentration (MIC) was determined for free and liposomal forms of both drugs. Minimum Bactericidal Concentration (MBC) was determined at concentrations 1, 2 and 4 times MIC. Average diameter of liposomes was 131.88 nm and encapsulation efficiency for cefepime and ceftazidime were 2.29% end 5.77%, respectively. Improved stability was obtained when liposome formulations were prepared with a 50% molar ratio for cholesterol in relation to the phospholipid. MIC for liposomal antibiotics for both drugs were 50% lower than that of the free drug, demonstrating that liposomal drug delivery systems may contribute to increase the antibacterial activity of these drugs. PMID:24031917

  17. EXPERIMENTAL LIPOSOMAL VIRAL VACCINE SAFETY

    Directory of Open Access Journals (Sweden)

    Romanova OA

    2016-12-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Akiho Fukuda

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

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

    Directory of Open Access Journals (Sweden)

    Federico Perche

    2013-01-01

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

  1. 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.

  2. 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.

  3. Spontaneous pneumothorax

    Directory of Open Access Journals (Sweden)

    Davari R

    1996-07-01

    Full Text Available A case with bilateral spontaneous pneumothorax was presented. Etiology, mechanism, and treatment were discussed on the review of literature. Spontaneous Pneumothorax is a clinical entity resulting from a sudden non traumatic rupture of the lung. Biach reported in 1880 that 78% of 916 patients with spontaneous pneumothorax had tuberculosis. Kjergaard emphasized 1932 the primary importance of subpleural bleb disease. Currently the clinical spectrum of spontaneous pneumothorax seems to have entered a third era with the recognition of the interstitial lung disease and AIDS as a significant etiology. Standard treatment is including: observation, thoracocentesis, tube thoracostomy. Chemical pleurodesis, bullectomy or wedge resection of lung with pleural abrasion and occasionally pleurectomy. Little information has been reported regarding the efficacy of such treatment in spontaneous pneumothorax secondary to non bleb disease

  4. Tyrosol-based liposomal behavior: Size, z-potential, TEM, QCM-D and fluorescence analysis

    Science.gov (United States)

    In our continued efforts to create biobased antioxidants for the food industry, we have used phospholipase D from Streptomyces sp. to create hydroxytyrosol and tyrosol phospholipids. Extrusion methods proved that both hydroxytyrosol phospholipids and tyrosol phospholipids each formed liposomes that ...

  5. 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

  6. Spontaneous Grammar Explanations.

    Science.gov (United States)

    Tjoo, Hong Sing; Lewis, Marilyn

    1998-01-01

    Describes one New Zealand university language teacher's reflection on her own grammar explanations to university-level students of Bahasa Indonesian. Examines form-focused instruction through the teacher's spontaneous answers to students' questions about the form of the language they are studying. The teacher's experiences show that it takes time…

  7. Vesicular melatonin efficiently downregulates sodium fluoride-induced rat hepato- and broncho- TNF-α, TGF-β expressions, and associated oxidative injury: a comparative study of liposomal and nanoencapsulated forms

    Directory of Open Access Journals (Sweden)

    Sana S

    2017-05-01

    Full Text Available Suvomoy Sana, Swarupa Ghosh, Nirmalendu Das, Sibani Sarkar, Ardhendu Kumar Mandal Drug Development, Diagnostics and Biotechnology, CSIR-Indian Institute of Chemical Biology, West Bengal, India Abstract: The importance of fluoride as a natural and industrial toxicant is recognized worldwide. We evaluated the regulating role and biological effect of vesicular (liposomal and nanoencapsulated melatonin (N-acetyl-5-methoxytryptamine for drug delivery and controlled release on the depletion of inflammatory mediators, as well as oxidative damage in sodium fluoride (NaF-treated lungs and liver. Hepatic and bronchial damage was induced in Swiss albino rats with a single acute ingestion of NaF (48 mg/kg body weight, oral gavage. NaF exposure caused the generation of reactive oxygen species (ROS; upregulation of TNF-α and TGF-β; decreased activities of antioxidant systems (glutathione, glutathione-S-transferase, superoxide dismutase, catalase, succinate dehydrogenase, membrane microviscosity, and membrane potential; increased activity of lipid peroxidation and nicotinamide adenine dinucleotide hydride oxidase; and increased hepatic and nephrite toxicities (P<0.001 compared to those in normal animals. Charge (–ve/+ve-specific single liposomal (dicetyl phosphate/stearylamine and nanoencapsulated melatonin (4.46 mg/kg body weight, intravenous treatments (2 hours after NaF exposure significantly (P<0.01/0.001 and maximally (P<0.001 inhibited all alterations developed in NaF-mediated oxidative injuries in rat liver (+ve and lungs (–ve, demonstrating their strong free radical scavenging, antioxidant and antigenotoxic properties, and vesicular efficiencies of targeting. Overall, these results suggest that nanoencapsulated melatonin might be considered as a more powerful remedial therapy in comparison to liposomes, in terms of its efficacy in regulating NaF-intoxicated oxidative injury. Keywords: sodium fluoride, reactive oxygen species, inflammatory

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

    African Journals Online (AJOL)

    From 1970s, supercritical fluids technology (SCF) has been utilized in liposomal preparation because of its friendliness, nontoxicity to the environment and its possibility to achieve solvent-free liposomes and industrial-scale of liposome production under the conditions of current good manufacturing practice (cGMP).

  9. Tat-functionalized liposomes for the treatment of meningitis: an in vitro study

    Science.gov (United States)

    Bartomeu Garcia, Caterina; Shi, Di; Webster, Thomas J

    2017-01-01

    Bacterial meningitis has become a global concern, because of the emergence of antibiotic-resistant bacteria. It has been demonstrated that liposomes can enter bacteria, thus providing a possible treatment for numerous infections, including meningitis. Fusogenic liposomes are pH-sensitive with a high capacity to fuse with the bacteria membrane and promote intracellular drug release. Moreover, this ability can be improved by using cell-penetrating peptides (such as Tat47–57, which is a peptide derived from the Tat protein of HIV). The purpose of this in vitro study was to demonstrate for the first time the ability of the presently prepared fusogenic liposomes, which were spherical particles with a diameter of 100 nm loaded with antibiotics and functionalized with-cell penetrating peptides (Tat47–57), to fight the main bacteria that cause meningitis. For this, vancomycin, methicillin, and ampicillin antibiotics were loaded inside fusogenic liposomes to fight Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, and Escherichia coli. Antibacterial activity of Tat-functionalized and nonfunctionalized liposomes loaded with antibiotics was tested by determining bacteria colony-forming units and growth-curve assays coupled with live/dead assays using fluorescence microscopy. Results showed a remarkable decrease in antibiotic minimum inhibitory concentration when all of the bacteria were treated with these novel liposomes, especially for the functionalized liposomes loaded with methicillin. With antibiotic concentrations of 1.7–3 µg/mL for Tat-functionalized liposomes loaded with methicillin, the bacteria population was totally eradicated. Cytotoxicity tests with astrocytes and endothelial cells, major cellular components of the blood–brain barrier, were also performed for all of the liposomes, including free antibiotic and the Tat peptide. Results showed much promise for the further study of the presently formulated liposomes to treat meningitis

  10. Environment-responsive multifunctional liposomes.

    Science.gov (United States)

    Kale, Amit A; Torchilin, Vladimir P

    2010-01-01

    Liposomal nanocarriers anchored with a cell-penetrating peptide and a pH-sensitive PEG-shield where later has ability to provide simultaneously better systemic circulation and site-specific exposure of cell penetrating peptide. PEG chains were incorporated into the liposome membrane via the PEG-attached phosphatidylethanolamine (PE) residue with PEG and PE being conjugated with the lowered pH-degradable hydrazone bond (PEG-HZ-PE), while cell-penetrating peptide (TATp) was added as TATp-PEG-PE conjugate. Under normal conditions, liposome-grafted PEG "shielded" liposome-attached TATp moieties, since the PEG spacer for TATp attachment (PEG(1000)) was shorter than protective PEG(2000). PEGylated liposomes accumulate in targets via the EPR effect, but inside the "acidified" tumor or ischemic tissues lose their PEG coating because of the lowered pH-induced hydrolysis of HZ and penetrate inside cells via the now-exposed TATp moieties. pH-responsive behavior of these constructs is successfully tested in cell cultures in vitro as well as in tumors in experimental mice in vivo. These nanocarriers also showed enhanced pGFP transfection efficiency upon intratumoral administration in mice, compared to control pH nonsensitive counterpart. These results can be considered as an important step in the development of tumor-specific stimuli-sensitive drug and gene delivery systems.

  11. Radiolabeling and Quantitative In Vivo SPECT/CT Imaging Study of Liposomes Using the Novel Iminothiolane-99mTc-Tricarbonyl Complex

    Directory of Open Access Journals (Sweden)

    Zoltán Varga

    2017-01-01

    Full Text Available The in vivo biodistribution of liposomal formulations greatly influences the pharmacokinetics of these novel drugs; therefore the radioisotope labeling of liposomes and the use of nuclear imaging methods for in vivo studies are of great interest. In the present work, a new procedure for the surface labeling of liposomes is presented using the novel 99mTc-tricarbonyl complex. Liposomes mimicking the composition of two FDA approved liposomal drugs were used. In the first step of the labeling, thiol-groups were formed on the surface of the liposomes using Traut’s reagent, which were subsequently used to bind 99mTc-tricarbonyl complex to the liposomal surface. The labeling efficiency determined by size exclusion chromatography was 95%, and the stability of the labeled liposomes in bovine serum was found to be 94% over 2 hours. The obtained specific activity was 50 MBq per 1 μmol lipid which falls among the highest values reported for 99mTc labeling of liposomes. Quantitative in vivo SPECT/CT biodistribution studies revealed distinct differences between the labeled liposomes and the free 99mTc-tricarbonyl, which indicates the in vivo stability of the labeling. As the studied liposomes were non-PEGylated, fast clearance from the blood vessels and high uptake in the liver and spleen were observed.

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

    International Nuclear Information System (INIS)

    Nakamura, Hiroyuki; Miyajima, Yusuke; Kuwata, Yasuhiro; Maruyama, Kazuo; Masunaga, Shinichiro; Ono, Koji

    2006-01-01

    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-CO 2 H 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 10 B concentration of 22 ppm in tumor tissues was achieved by the injection of Tf-PEG-CL liposome at 7.2 mg/kg body weight 10 B 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. 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

    depleted, cationic, anionic, and zwitterionic lipid compositions. We demonstrate high in vivo stability of 64Cu-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......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 64Cu2+ 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...

  14. Filter-extruded liposomes revisited

    DEFF Research Database (Denmark)

    Hinna, Askell; Steiniger, Frank; Hupfeld, Stefan

    2016-01-01

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

  15. Preparation and quality evaluation of LHRHa-targeted Brucea javanica oil liposomes

    Directory of Open Access Journals (Sweden)

    Xiao-juan LIU

    2013-07-01

    Full Text Available Objective To prepare luteinizing hormone-releasing hormone a (LHRHa targeted Bruceajavanicaliposomes and evaluate its quality. Methods The LHRHa-targeted Bruceajavanicaliposome was prepared by thin layer dispersion together with biotin¬streptavidin bridge method. The optimum formation was selected by means of orthogonal design of experiment. The morphology of liposome was observed with transmission electron microscope. Zetasizer Nano ZS analyzer was used to measure the particle size and zeta potential. The entrapment efficiency was determined by ultra-violet spectroscopy and column chromatography. Centrifugal acceleration experiment and determination of leak rate were performed to prove the liposome stability. The targeting ability of liposome was appraised by cell experiment in vitro. Results The formed optimum formula was as follows: the ratio of lecithin to cholesterol was 4:1, Brucea javanicaoil:lipid was 3:10, DSPE-PEG (2000-Biotin:lecithin content was 3%, ultrasonic-homogenized for 8 minutes. Liposomes were round in shape, the average diameter and zeta potential of liposome were 155.1±14.5mm and –(24.1±0.54 mV, respectively. The average entrapment efficiency was 92.2%. Binding capacity with the A2780/DDP cell line in the LHRHa-targeted liposomes was 2.7 times higher than that in the non-targeting liposomes. Conclusion The technique of preparing LHRHa-targeted Bruceajavanicaliposome is suitable, and high in entrapment efficiency, with good stability and targeting ability.

  16. Pore formation by T3SS translocators: liposome leakage assay.

    Science.gov (United States)

    Faudry, Eric; Perdu, Caroline; Attrée, Ina

    2013-01-01

    Gram-negative bacteria utilize a dedicated membrane-embedded apparatus, the type III secretion system (T3SS), to inject proteins into host cells. The passage of the proteins across the target membrane is accomplished by a proteinaceous pore-the translocon-formed within the host-cell cytoplasmic membrane. Translocators bound to their chaperones can be expressed in Escherichia coli and subsequently dissociated from the chaperone by guanidine treatment. The pore formation properties of the translocators can then be studied by an in-vitro liposome leakage assay. Sulforhodamine-B is encapsulated within lipid vesicles during liposome preparation. At high concentration, this fluorochrome exhibits self-quenching limiting fluorescence emission. Upon pore formation, liposome leakage leads to the dilution of Sulforhodamine-B in the medium and fluorescence emission increases. Alternatively, fluorochromes coupled to large dextran molecules can be encapsulated in order to estimate pore dimensions. Here we describe protein expression and purification, dye-liposome preparation, and leakage assay conditions.

  17. Topical liposomal azithromycin in the treatment of acute cutaneous leishmaniasis.

    Science.gov (United States)

    Rajabi, Omid; Layegh, Pouran; Hashemzadeh, Sara; Khoddami, Mohsen

    2016-09-01

    Cutaneous leishmaniasis (CL) treatment is based on pentavalant antimony (sbv) drugs which are accompanied by many side effects and are facing ever-increasing resistance. Topical treatment of CL is an attractive alternative avoiding toxicities of parenteral therapy while being administered through a simple painless route. The liposomal formulations of different drugs have recently been increasingly used in the treatment of several types of leishmaniasis. The efficacy of a topical liposomal azithromycin formulation was compared with intralesional meglumine antimoniate (glucantime) in the treatment of CL. Sixty-six patients with 97 lesions who met our inclusion criteria were randomly divided into two groups. One group was administered with the topical liposomal form of azithromycin twice daily. The other group was treated by weekly intralesional injections of glucantime with a volume of 0.5-2 cm3 into each lesion till complete blanching of the lesion occurred. Clinical evaluations were performed weekly during the treatment course (8 weeks) by a single dermatologist for both groups. Per-protocol analysis showed no statistically significant difference between the two groups (p = 0.84, 95% confidence interval (CI) = 0.764 (0.714-0.821). Serious drug side effects were not observed in either group. Topical liposomal azithromycin has the same efficacy as intralesional glucantime in the treatment of CL. © 2016 Wiley Periodicals, Inc.

  18. Improved therapeutic benefits of doxorubicin by entrapment in anionic liposomes.

    Science.gov (United States)

    Forssen, E A; Tökés, Z A

    1983-02-01

    When used as drug carriers, anionic liposomes can reduce the chronic cardiac toxicity and increase the antileukemic activity of doxorubicin (DXN; Adriamycin). Continuing investigations, reported here, have now established the therapeutic benefits of this mode of drug delivery. Liposome encapsulation caused a prolonged elevation in DXN plasma levels and a 2-fold reduction in the exposure of cardiac tissue to the drug. This reduction, however, was not proportional to the substantial decrease in chronic heart toxicity observed in the earlier study. In vivo studies have demonstrated that the entrapped drug retains its full activity against Sarcoma 180 and significantly increases its action against Lewis lung carcinoma, as measured by reduced tumor volume. The increased antineoplastic activity was again not proportional to the increased association of drug with tumor tissue. The effect of liposome entrapment on the immune-suppressive activity of DXN was also examined to determine if factors other than the direct delivery of drug to tumor tissue might improve the therapeutic response. The suppression of the humoral immune response and peripheral leukocyte counts by free DXN was nearly abolished when the drug was administered in the liposome form. These experiments suggest that the improved therapeutic effect of encapsulation may be the outcome of three different mechanisms: (a) altered disposition into subcellular compartments, which reduces cardiotoxicity; (b) increased plasma drug exposure to tumor cells; and (c) significant reduction in the immune suppressive activity of DXN.

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

    Directory of Open Access Journals (Sweden)

    Oula Penate Medina

    2011-01-01

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

  20. Cell-sized liposomes reveal how actomyosin cortical tension drives shape change.

    Science.gov (United States)

    Carvalho, Kevin; Tsai, Feng-Ching; Tsai, Feng C; Lees, Edouard; Voituriez, Raphaël; Koenderink, Gijsje H; Sykes, Cecile

    2013-10-08

    Animal cells actively generate contractile stress in the actin cortex, a thin actin network beneath the cell membrane, to facilitate shape changes during processes like cytokinesis and motility. On the microscopic scale, this stress is generated by myosin molecular motors, which bind to actin cytoskeletal filaments and use chemical energy to exert pulling forces. To decipher the physical basis for the regulation of cell shape changes, here, we use a cell-like system with a cortex anchored to the outside or inside of a liposome membrane. This system enables us to dissect the interplay between motor pulling forces, cortex-membrane anchoring, and network connectivity. We show that cortices on the outside of liposomes either spontaneously rupture and relax built-up mechanical stress by peeling away around the liposome or actively compress and crush the liposome. The decision between peeling and crushing depends on the cortical tension determined by the amount of motors and also on the connectivity of the cortex and its attachment to the membrane. Membrane anchoring strongly affects the morphology of cortex contraction inside liposomes: cortices contract inward when weakly attached, whereas they contract toward the membrane when strongly attached. We propose a physical model based on a balance of active tension and mechanical resistance to rupture. Our findings show how membrane attachment and network connectivity are able to regulate actin cortex remodeling and membrane-shape changes for cell polarization.

  1. “Smart” Drug Carriers: PEGylated TATp-Modified pH-Sensitive Liposomes

    Science.gov (United States)

    KALE, AMIT A.; TORCHILIN, VLADIMIR P.

    2012-01-01

    To engineer drug carriers capable of spontaneous accumulation in tumors and ischemic areas via the enhanced permeability and retention (EPR) effect and further penetration and drug delivery inside tumor or ischemic cells via the action of the cell-penetrating peptide (CPP), we have prepared liposomes simultaneously bearing on their surface CPP (TAT peptide, TATp) moieties and protective PEG chains. PEG chains were incorporated into the liposome membrane via the PEG-attached phosphatidylethanolamine (PE) residue with PEG and PE being conjugated with the lowered pH-degradable hydrazone bond (PEG-HZ-PE). Under normal conditions, liposome-grafted PEG “shielded” liposome-attached TATp moieties since the PEG spacer for TATp attachment (PEG1000) was shorter than protective PEG2000. PEGy-lated liposomes are expected to accumulate in targets via the EPR effect, but inside the “acidified” tumor or ischemic tissues lose their PEG coating due to the lowered pH-induced hydrolysis of HZ and penetrate inside cells via the now-exposed TATp moieties. This concept is shown here to work in cell cultures in vitro as well as in ischemic cardiac tissues in the Langendorff perfused rat heart model and in tumors in experimental mice in vivo. PMID:18027240

  2. "Smart" drug carriers: PEGylated TATp-modified pH-sensitive liposomes.

    Science.gov (United States)

    Kale, Amit A; Torchilin, Vladimir P

    2007-01-01

    To engineer drug carriers capable of spontaneous accumulation in tumors and ischemic areas via the enhanced permeability and retention (EPR) effect and further penetration and drug delivery inside tumor or ischemic cells via the action of the cell-penetrating peptide (CPP), we have prepared liposomes simultaneously bearing on their surface CPP (TAT peptide, TATp) moieties and protective PEG chains. PEG chains were incorporated into the liposome membrane via the PEG-attached phosphatidylethanolamine (PE) residue with PEG and PE being conjugated with the lowered pH-degradable hydrazone bond (PEG-HZ-PE). Under normal conditions, liposome-grafted PEG "shielded" liposome-attached TATp moieties since the PEG spacer for TATp attachment (PEG(1000)) was shorter than protective PEG(2000). PEGylated liposomes are expected to accumulate in targets via the EPR effect, but inside the "acidified" tumor or ischemic tissues lose their PEG coating due to the lowered pH-induced hydrolysis of HZ and penetrate inside cells via the now-exposed TATp moieties. This concept is shown here to work in cell cultures in vitro as well as in ischemic cardiac tissues in the Langendorff perfused rat heart model and in tumors in experimental mice in vivo.

  3. Spontaneous compactification to homogeneous spaces

    International Nuclear Information System (INIS)

    Mourao, J.M.

    1988-01-01

    The spontaneous compactification of extra dimensions to compact homogeneous spaces is studied. The methods developed within the framework of coset space dimensional reduction scheme and the most general form of invariant metrics are used to find solutions of spontaneous compactification equations

  4. Spontaneous deregulation

    NARCIS (Netherlands)

    Edelman, Benjamin; Geradin, Damien

    Platform businesses such as Airbnb and Uber have risen to success partly by sidestepping laws and regulations that encumber their traditional competitors. Such rule flouting is what the authors call “spontaneous private deregulation,” and it’s happening in a growing number of industries. The authors

  5. Analysis of liposomes using asymmetrical flow field-flow fractionation

    DEFF Research Database (Denmark)

    Kuntsche, Judith; Decker, Christiane; Fahr, Alfred

    2012-01-01

    of larger vesicles was underestimated. Imbalance in the osmolality between the inner and outer aqueous phase resulted in liposome swelling after dilution in hypoosmotic carrier liquids. In contrast, liposome shrinking under hyperosmotic conditions was barely visible. The liposomes themselves eluted...

  6. Liposomes derivatized with multimeric copies of KCCYSL peptide as targeting agents for HER-2-overexpressing tumor cells

    Directory of Open Access Journals (Sweden)

    Ringhieri P

    2017-01-01

    Full Text Available Paola Ringhieri,1 Silvia Mannucci,2 Giamaica Conti,2 Elena Nicolato,2 Giulio Fracasso,3 Pasquina Marzola,4 Giancarlo Morelli,1 Antonella Accardo1 1Department of Pharmacy and Interuniversity Research Centre on Bioactive Peptides (CIRPeB, University of Naples “Federico II”, Napoli, 2Department of Neurological Biomedical and Movement Sciences, 3Section of Immunology, Department of Medicine, 4Department of Informatics, University of Verona, Verona, Italy Abstract: Mixed liposomes, obtained by coaggregation of 1,2-dioleoyl-sn-glycero-3-phosphocholine and of the synthetic monomer containing a gadolinium complex ([C18]2DTPA[Gd] have been prepared. Liposomes externally decorated with KCCYSL (P6.1 peptide sequence in its monomeric, dimeric, and tetrameric forms are studied as target-selective delivery systems toward cancer cells overexpressing human epidermal growth factor receptor-2 (HER-2 receptors. Derivatization of liposomal surface with targeting peptides is achieved using the postmodification method: the alkyne-peptide derivative Pra-KCCYSL reacts, through click chemistry procedures, with a synthetic surfactant modified with 1, 2, or 4 azido moieties previously inserted in liposome formulation. Preliminary in vitro data on MDA-MB-231 and BT-474 cells indicated that liposomes functionalized with P6.1 peptide in its tetrameric form had better binding to and uptake into BT-474 cells compared to liposomes decorated with monomeric or dimeric versions of the P6.1 peptide. BT-474 cells treated with liposomes functionalized with the tetrameric form of P6.1 showed high degree of liposome uptake, which was comparable with the uptake of anti-HER-2 antibodies such as Herceptin. Moreover, magnetic MRI experiments have demonstrated the potential of liposomes to act as MRI contrast agents. Keywords: anti-HER2 liposomes, target peptide, KCCYSL peptide, breast cancer, click chemistry, branched peptides 

  7. General and programmable synthesis of hybrid liposome/metal nanoparticles

    OpenAIRE

    Lee, Jin-Ho; Shin, Yonghee; Lee, Wooju; Whang, Keumrai; Kim, Dongchoul; Lee, Luke P.; Choi, Jeong-Woo; Kang, Taewook

    2016-01-01

    Hybrid liposome/metal nanoparticles are promising candidate materials for biomedical applications. However, the poor selectivity and low yield of the desired hybrid during synthesis pose a challenge. We designed a programmable liposome by selective encoding of a reducing agent, which allows self-crystallization of metal nanoparticles within the liposome to produce stable liposome/metal nanoparticles alone. We synthesized seven types of liposome/monometallic and more complex liposome/bimetalli...

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

    Directory of Open Access Journals (Sweden)

    Neda Bavarsad

    2016-01-01

    Full Text Available 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.

  9. Protein immobilization on the surface of liposomes via carbodiimide activation in the presence of N-hydroxysulfosuccinimide.

    Science.gov (United States)

    Bogdanov, A A; Klibanov, A L; Torchilin, V P

    1988-04-25

    A method of the covalent immobilization of proteins on the surface of liposomes, containing 10% (by mol) of N-glutaryl phosphatidylethanolamine, is described. Carboxylic groups of liposomal N-glutaryl phosphatidylethanolamine were activated in the presence of water-soluble carbodiimide and N-hydroxysulfosuccinimide and reacted subsequently with protein amino groups. The liposome-protein conjugates formed contained up to 5 x 10(-4) mol protein/mol lipid. Lectins (RCA1 and WGA) upon immobilization on liposomes retained saccharide specificity and the ability to agglutinate red blood cells. The immobilization of mouse monoclonal IgG in a ratio of 3.5 x 10(-4) mol IgG/mol lipid was achieved. The liposome activation in the absence of N-hydroxysulfosuccinimide resulted in a 2-fold decrease of protein coupling yields.

  10. The adjuvant mechanism of cationic dimethyldioctadecylammonium liposomes

    DEFF Research Database (Denmark)

    Korsholm, Karen Smith; Agger, Else Marie; Foged, Camilla

    2007-01-01

    Cationic liposomes are being used increasingly as efficient adjuvants for subunit vaccines but their precise mechanism of action is still unknown. Here, we investigated the adjuvant mechanism of cationic liposomes based on the synthetic amphiphile dimethyldioctadecylammonium (DDA). The liposomes...... concentrations. This efficient adsorption onto the liposomes led to an enhanced uptake of OVA by BM-DCs as assessed by flow cytometry and confocal fluorescence laser-scanning microscopy. This was an active process, which was arrested at 4 degrees and by an inhibitor of actin-dependent endocytosis, cytochalasin D....... In vivo studies confirmed the observed effect because adsorption of OVA onto DDA liposomes enhanced the uptake of the antigen by peritoneal exudate cells after intraperitoneal injection. The liposomes targeted antigen preferentially to antigen-presenting cells because we only observed a minimal uptake...

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

    Directory of Open Access Journals (Sweden)

    Nayyer Karimi

    2015-06-01

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

  12. Preparation and ocular pharmacokinetics of ganciclovir liposomes

    OpenAIRE

    Shen, Yan; Tu, Jiasheng

    2007-01-01

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

  13. Liposomes - experiment of magnetic resonance imaging application

    International Nuclear Information System (INIS)

    Mathieu, S.

    1987-01-01

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

  14. Evaluation of Extrusion Technique for Nanosizing Liposomes

    Directory of Open Access Journals (Sweden)

    Sandy Gim Ming Ong

    2016-12-01

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

  15. Liposomal Drug Delivery of Anticancer Agents

    DEFF Research Database (Denmark)

    Pedersen, Palle Jacob

    In the first part of the thesis the work towards a new generation of liposomal drug delivery systems for anticancer agents is described. The drug delivery system takes advantage of the elevated level of secretory phospholipase A2 (sPLA2) IIA in many tumors and the enhanced permeability......-trans retinoic acid, α-tocopheryl succinate and calcitriol were examined for their ability to be incorporated into the investigated drug delivery system and syntheses of the phospholipid prodrugs are described. The majority of the phospholipid prodrugs were able to form particles with diameters close to 100 nm...... that upon sPLA2 triggering the formulated phospholipid prodrugs displayed IC50 values in range from 3–36 μM and complete cell death was observed when higher drug concentrations were applied. Promising for the drug delivery system the majority of the phospholipid prodrugs remain non-toxic in the absence...

  16. Development of curcumin liposome formulations using polyol dilution method

    OpenAIRE

    Lalana Kongkaneramit; Porntipa Aiemsum-ang; Prartana Kewsuwan

    2016-01-01

    This study was aimed to formulate curcumin liposomes (CLs) by using polyol dilution method which is advantageous for no residue of organic solvent. CLs were the mixture of hydrogenated phosphatidylcholine (PC) and cholesterol (CH) at the molar ratio of 9:1. Propylene glycol (PG), glycerin, and polyethylene glycol 400 (PEG-400) were used as polyol solvent. Extrusion was applied after the suspension formed. The amount of polyol and curcumin and preparing temperature were investigate...

  17. Laccases stabilization with phosphatidylcholine liposomes

    OpenAIRE

    Martí, M.; Zille, Andrea; Paulo, Artur Cavaco; Parra, J. L.; Coderch, L.

    2012-01-01

    In recent years, there has been an upsurge of interest in enzyme treatment of textile fibres. Enzymes are globular proteins whose catalytic function is due to their three dimensional structure. For this reason, stability strategies make use of compounds that avoid dismantling or distorting protein 3D structures. This study is concerned with the use of microencapsulation techniques to optimize enzyme stabilization. Laccases were embedded in phophatidylcholine liposomes and their encaps...

  18. Sirolimus encapsulated liposomes for cancer therapy: physicochemical and mechanical characterization of sirolimus distribution within liposome bilayers.

    Science.gov (United States)

    Onyesom, Ichioma; Lamprou, Dimitrios A; Sygellou, Lamprini; Owusu-Ware, Samuel K; Antonijevic, Milan; Chowdhry, Babur Z; Douroumis, Dennis

    2013-11-04

    Sirolimus has recently been introduced as a therapeutic agent for breast and prostate cancer. In the current study, conventional and Stealth liposomes were used as carriers for the encapsulation of sirolimus. The physicochemical characteristics of the sirolimus liposome nanoparticles were investigated including the particle size, zeta potential, stability and membrane integrity. In addition atomic force microscopy was used to study the morphology, surface roughness and mechanical properties such as elastic modulus deformation and deformation. Sirolimus encapsulation in Stealth liposomes showed a high degree of deformation and lower packing density especially for dipalmitoyl-phosphatidylcholine (DPPC) Stealth liposomes compared to unloaded. Similar results were obtained by differential scanning calorimetry (DSC) studies; sirolimus loaded liposomes were found to result in a distorted state of the bilayer. X-ray photon electron (XPS) analysis revealed a uniform distribution of sirolimus in multilamellar DPPC Stealth liposomes compared to a nonuniform, greater outer layer lamellar distribution in distearoylphosphatidylcholine (DSPC) Stealth liposomes.

  19. 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.

  20. Continuous-Flow Production of Injectable Liposomes via a Microfluidic Approach

    Directory of Open Access Journals (Sweden)

    Alessandra Zizzari

    2017-12-01

    Full Text Available Injectable liposomes are characterized by a suitable size and unique lipid mixtures, which require time-consuming and nonstraightforward production processes. The complexity of the manufacturing methods may affect liposome solubility, the phase transition temperatures of the membranes, the average particle size, and the associated particle size distribution, with a possible impact on the drug encapsulation and release. By leveraging the precise steady-state control over the mixing of miscible liquids and a highly efficient heat transfer, microfluidic technology has proved to be an effective and direct methodology to produce liposomes. This approach results particularly efficient in reducing the number of the sizing steps, when compared to standard industrial methods. Here, Microfluidic Hydrodynamic Focusing chips were produced and used to form liposomes upon tuning experimental parameters such as lipids concentration and Flow-Rate-Ratios (FRRs. Although modelling evidenced the dependence of the laminar flow on the geometric constraints and the FRR conditions, for the specific formulation investigated in this study, the lipids concentration was identified as the primary factor influencing the size of the liposomes and their polydispersity index. This was attributed to a predominance of the bending elasticity modulus over the vesiculation index in the lipid mixture used. Eventually, liposomes of injectable size were produced using microfluidic one-pot synthesis in continuous flow.

  1. Stable archaeal tetraether lipid liposomes for photodynamic application: transfer of carboxyfluorescein to cultured T84 tumor cells

    Directory of Open Access Journals (Sweden)

    Anton Oertl

    2017-01-01

    Full Text Available Background: Archaeal membranes have phytanyl ether lipids instead of common fatty acid-glycerol esters in bacterial and eukaryotic cells. Sulfolobus and Thermoplasma species have unique membrane-spanning tetraether lipids (TEL, which form stable liposomes. Recently, we cultured Thermoplasma species from the Indonesian volcano Tangkuban Perahu and isolated TEL. The purpose of this in vitro study is to investigate the transfer of fluorescent dye from stable TEL liposomes to cultured colon carcinoma cells.Methods: TEL was extracted from cultured cells with chloroform-methanol (1:1, then it was fractionated and purified via diethylaminoethyl-cellulose-acetate columns and activated charcoal for the formation of stable liposomes. For the fluorescence exchange assay, TEL liposomes were loaded with water-soluble carboxyfluorescein (CF. Staining experiments were conducted with various cell cultures, and T84 colon carcinoma cells were chosen for the main experiments. Liposome stability was tested by light scattering and electron microscopic size determinations as well as by unspecific CF release at low pH (6.0–7.4 and increased temperature  (4–50°C/70°C.Results: TEL liposomes exhibit high stability and extremely low proton permeability at low pH. CF staining of cultured T84 colon carcinoma cells appeares more intensive from TEL liposomes than from dipalmitoylphosphatidylcholine liposomes.Conclusion: The results of this in vitro study demonstrate CF staining of colon carcinoma cells and high stability of TEL liposomes at low pH, matching the condition in the gastro-intestinal (GI route and in the urogentital (UG tract. For this reason, in vivo studies on liposomal fluorescent photosensitizers for topical application of photodynamic cancer therapy in the GI and UG tracts should be carried out.

  2. Liposomes of dimeric artesunate phospholipid: A combination of dimerization and self-assembly to combat malaria.

    Science.gov (United States)

    Ismail, Muhammad; Ling, Longbing; Du, Yawei; Yao, Chen; Li, Xinsong

    2018-05-01

    Artemisinin and its derivatives are highly effective drugs in the treatment of P. falciparum malaria. However, their clinical applications face challenges because of short half-life, poor bioavailability and growing drug resistance. In this article, novel dimeric artesunate phospholipid (Di-ART-GPC) based liposomes were developed by combination of dimerization and self-assembly to address these shortcomings. Firstly, Di-ART-GPC conjugate was synthesized by a facile esterification of artesunate (ART) and glycerophosphorylcholine (GPC) and confirmed by MS, 1 H NMR and 13 C NMR. The conjugate was then assembled to form liposomes without excipient by thin film hydration method. The assembled Di-ART-GPC liposomes have typical multilamellar vesicle structure with bilayer morphology as determined by transmission electron microscopy (TEM) and cryogenic electron microscopy (cryo-EM). Moreover, the liposomes displayed an average hydrodynamic diameter of 190 nm and negative zeta potential at -20.35 mV as determined by Zetasizer. The loading capacity of ART was calculated approximately 77.6% by weight with this liposomal formulation after a simple calculation. In vitro drug release and degradation results showed that the Di-ART-GPC liposomes were stable in neutral physiological conditions but effectively degraded to release parent ART in simulated weakly acidic microenvironment. In vivo pharmacokinetics study revealed that Di-ART-GPC liposomes and conjugate have longer retention half-life in bloodstream. Importantly, Di-ART-GPC liposomes (IC 50 0.39 nM) and the conjugate (IC 50 1.90 nM) demonstrated excellent in vitro antiplasmodial activities without causing hemolysis of erythrocytes, which were superior to free ART (IC 50 5.17 nM) and conventional ART-loaded liposomes (IC 50 3.13 nM). Furthermore, the assembled liposomes resulted in enhanced parasites killing in P. berghei-infected mice in vivo with delayed recrudescence and improved survivability

  3. Bacterial Toxin-Triggered Drug Release from Gold Nanoparticle-Stabilized Liposomes for the Treatment of Bacterial Infection

    Science.gov (United States)

    Pornpattananangkul, Dissaya; Zhang, Li; Olson, Sage; Aryal, Santosh; Obonyo, Marygorret; Vecchio, Kenneth; Huang, Chun-Ming; Zhang, Liangfang

    2011-01-01

    We report a new approach to selectively delivering antimicrobials to the sites of bacterial infections by utilizing bacterial toxins to activate drug release from gold nanoparticle-stabilized phospholipid liposomes. The binding of chitosan modified gold nanoparticles to the surface of liposomes can effectively prevent them from fusing with one another and from undesirable payload release in regular storage or physiological environments. However, once these protected liposomes “see” bacteria that secrete toxins, the toxins will insert into the liposome membranes and form pores, through which the encapsulated therapeutic agents are released. The released drugs subsequently impose antimicrobial effects on the toxin-secreting bacteria. Using methicillin-resistant Staphycoccus aureus (MRSA) as a model bacterium and vacomycin as a model anti-MRSA antibiotic, we demonstrate that the synthesized gold nanoparticle-stabilized liposomes can completely release the encapsulated vacomycin within 24 h in the presence of MRSA bacteria and lead to inhibition of MRSA growth as effective as an equal amount of vacomycin loaded liposomes (without nanoparticle stabilizers) and free vacomycin. This bacterial toxin enabled drug release from nanoparticle-stabilized liposomes provides a new, safe and effective approach for the treatment of bacterial infections. This technique can be broadly applied to treat a variety of infections caused by bacteria that secrete pore-forming toxins. PMID:21344925

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

    Science.gov (United States)

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

    2013-01-01

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

  5. Radionuclide imaging of liposomal drug delivery

    NARCIS (Netherlands)

    van der Geest, Tessa; Laverman, Peter; Metselaar, Josbert M.|info:eu-repo/dai/nl/244207690; Storm, G|info:eu-repo/dai/nl/073356328; Boerman, Otto C.

    2016-01-01

    Introduction: Ever since their discovery, liposomes have been radiolabeled to monitor their fate in vivo. Despite extensive preclinical studies, only a limited number of radiolabeled liposomal formulations have been examined in patients. Since they can play a crucial role in patient management, it

  6. Radionuclide imaging of liposomal drug delivery

    NARCIS (Netherlands)

    Geest, T. van der; Laverman, P.; Metselaar, J.M.; Storm, G.; Boerman, O.C.

    2016-01-01

    Ever since their discovery, liposomes have been radiolabeled to monitor their fate in vivo. Despite extensive preclinical studies, only a limited number of radiolabeled liposomal formulations have been examined in patients. Since they can play a crucial role in patient management, it is of

  7. 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...

  8. Intravesical liposome therapy for interstitial cystitis.

    Science.gov (United States)

    Tyagi, Pradeep; Kashyap, Mahendra; Majima, Tsuyoshi; Kawamorita, Naoki; Yoshizawa, Tsuyoshi; Yoshimura, Naoki

    2017-04-01

    Over the past two decades, there has been lot of interest in the use of liposomes as lipid-based biocompatible carriers for drugs administered by the intravesical route. The lipidic bilayer structure of liposomes facilitates their adherence to the apical membrane surface of luminal cells in the bladder, and their vesicular shape allows them to co-opt the endocytosis machinery for bladder uptake after instillation. Liposomes have been shown to enhance the penetration of both water-soluble and insoluble drugs, toxins, and oligonucleotides across the bladder epithelium. Empty liposomes composed entirely of the endogenous phospholipid, sphingomyelin, could counter mucosal inflammation and promote wound healing in patients suffering from interstitial cystitis. Recent clinical studies have tested multilamellar liposomes composed entirely of sphingomyelin as a novel intravesical therapy for interstitial cystitis. In addition, liposomes have been used as a delivery platform for the instillation of botulinum toxin in overactive bladder patients. The present review discusses the properties of liposomes that are important for their intrinsic therapeutic effect, summarizes the recently completed clinical studies with intravesical liposomes and covers the latest developments in this field. © 2017 The Japanese Urological Association.

  9. Methods for using redox liposome biosensors

    Science.gov (United States)

    Cheng, Quan; Stevens, Raymond C.

    2002-01-01

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

  10. Development of curcumin liposome formulations using polyol dilution method

    Directory of Open Access Journals (Sweden)

    Lalana Kongkaneramit

    2016-12-01

    Full Text Available This study was aimed to formulate curcumin liposomes (CLs by using polyol dilution method which is advantageous for no residue of organic solvent. CLs were the mixture of hydrogenated phosphatidylcholine (PC and cholesterol (CH at the molar ratio of 9:1. Propylene glycol (PG, glycerin, and polyethylene glycol 400 (PEG-400 were used as polyol solvent. Extrusion was applied after the suspension formed. The amount of polyol and curcumin and preparing temperature were investigated. The obtained suspensions were observed for appearance, size, size distribution, zeta potential, morphology, and percentage of entrapment. The results showed that type and amount of polyol had an impact on both liposomal size and the amount of entrapped curcumin, while preparing temperature was also an important factor. However, the solubility of lipids and drug in a given polyol should be considered because of loading efficiency in the formulation.

  11. Tumor uptake of /sup 67/Ga-carrying liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Ogihara, Izumi; Kojima, Shuji; Kubodera, Akiko; Jay, M.

    1986-02-01

    The in vivo distribution, excretion, and tumor localization of liposome-encapsulated /sup 67/Ga in normal and Ehrlich tumor (solid form)-bearing mice were studied. In normal mice, multilamellar vesicles (MLVs) were taken up mainly be the liver and spleen, whereas small, unilamellar vesicles (SUVs) exhibited a broader tissue distribution. When /sup 67/Ga was encapsulated in MLVs or SUVs, the excretion of the radiotracer in the urine and feces was less than that observed for free tracer at 72 h after i.v. administration. In tumor-bearing mice, SUVs were formed to accumulate preferentially in tumors. The tumor uptake of neutral, positive, and negative SUVs was 10%-13% of the administered dose per gram of tumor tissue at 24 h after their injection. These values were about three times higher than those found for free /sup 67/Ga-nitrilotriacetic acid trisodium salt (NTA) or /sup 67/Ga-citrate. Significant differences in tumor uptake due to different surface charges of liposomes were not observed. Enhanced tumor-to-blood and tumor-to-muscle ratios were also observed at 24 h after injection. These results suggest that /sup 67/Ga-carrying liposomes may be a useful for tumor imaging.

  12. Tumor uptake of 67Ga-carrying liposomes

    International Nuclear Information System (INIS)

    Ogihara, Izumi; Kojima, Shuji; Kubodera, Akiko; Jay, M.

    1986-01-01

    The in vivo distribution, excretion, and tumor localization of liposome-encapsulated 67 Ga in normal and Ehrlich tumor (solid form)-bearing mice were studied. In normal mice, multilamellar vesicles (MLVs) were taken up mainly be the liver and spleen, whereas small, unilamellar vesicles (SUVs) exhibited a broader tissue distribution. When 67 Ga was encapsulated in MLVs or SUVs, the excretion of the radiotracer in the urine and feces was less than that observed for free tracer at 72 h after i.v. administration. In tumor-bearing mice, SUVs were formed to accumulate preferentially in tumors. The tumor uptake of neutral, positive, and negative SUVs was 10%-13% of the administered dose per gram of tumor tissue at 24 h after their injection. These values were about three times higher than those found for free 67 Ga-nitrilotriacetic acid trisodium salt (NTA) or 67 Ga-citrate. Significant differences in tumor uptake due to different surface charges of liposomes were not observed. Enhanced tumor-to-blood and tumor-to-muscle ratios were also observed at 24 h after injection. These results suggest that 67 Ga-carrying liposomes may be a useful for tumor imaging. (orig.)

  13. 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 has been...... an important tool in the development of liposomal drugs. However, advanced imaging systems now provide new possibilities for non-invasive monitoring of liposome biodistribution in humans. Thus, advances in imaging and developments in liposome radiolabeling techniques allow us to enter a new 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...

  14. Vincristine liposomal--INEX: lipid-encapsulated vincristine, onco TCS, transmembrane carrier system--vincristine, vincacine, vincristine sulfate liposomes for injection, VSLI.

    Science.gov (United States)

    2004-01-01

    INEX Pharmaceuticals is developing a liposomal formulation of vincristine [Onco TCS, vincacine, VSLI, Vincristine sulfate liposomes for injection] for the treatment of relapsed aggressive non-Hodgkin's lymphoma (NHL) and other cancers. It is being developed using INEX's proprietary drug-delivery technology platform called the transmembrane carrier systems (TCS), which enables the targeted intracellular delivery of various therapeutic agents. Liposomal vincristine is expected to have certain advantages over the existing standard preparation of vincristine because the use of TCS technology enables the vincristine to circulate in the blood for longer, accumulate in the tumour, and be released over an extended period of time at the tumour site. The application of TCS technology to any agent, including vincristine, has the potential to increase the efficacy and decrease the side effects of the agent. INEX decided in 1998 to focus on gaining approval for liposomal vincristine in the treatment of relapsed aggressive NHL because no standard therapy was approved for this indication. In 1999, liposomal vincristine was granted accelerated development status by the US FDA, which enables the FDA to approve it based on the surrogate endpoint of a single clinical trial. In addition, the FDA granted liposomal vincristine fast track status in August 2000. In April 2001, INEX and Elan Corporation formed a joint venture for the development and commercialisation of liposomal vincristine, with both companies contributing assets to the venture including worldwide rights to the product and intellectual property rights. The joint venture was called IE Oncology. However, in June 2002, Elan announced that it was going to focus its business strategy on three specific areas, which would not include cancer therapies. INEX announced it had regained 100% ownership of liposomal vincristine in April 2003, by reacquiring the 19.9% equity interest held by Elan and in addition retaining a fully paid

  15. Catalase-loaded cisplatin-prodrug-constructed liposomes to overcome tumor hypoxia for enhanced chemo-radiotherapy of cancer.

    Science.gov (United States)

    Zhang, Rui; Song, Xuejiao; Liang, Chao; Yi, Xuan; Song, Guosheng; Chao, Yu; Yang, Yu; Yang, Kai; Feng, Liangzhu; Liu, Zhuang

    2017-09-01

    Aiming at improved therapeutic efficacies, the combination of chemotherapy and radiotherapy (chemo-radiotherapy) has been widely studied and applied in clinic. However, the hostile characteristics of tumor microenvironment such as hypoxia often limit the efficacies in both types of cancer therapies. Herein, catalase (CAT), an antioxidant enzyme, is encapsulated inside liposomes constituted by cisplatin (IV)-prodrug-conjugated phospholipid, forming CAT@Pt (IV)-liposome for enhanced chemo-radiotherapy of cancer. After being loaded inside liposomes, CAT within CAT@Pt (IV)-liposome shows retained and well-protected enzyme activity, and is able to trigger decomposition of H 2 O 2 produced by tumor cells, so as to produce additional oxygen for hypoxia relief. As the result, treatment of CAT@Pt (IV)-liposome induces the highest level of DNA damage in cancer cells after X-ray radiation compared to the control groups. In vivo tumor treatment further demonstrates a remarkably improved therapeutic outcome in chemo-radiotherapy with such CAT@Pt (IV)-liposome nanoparticles. Hence, an exquisite type of liposome-based nanoparticles is developed in this work by integrating cisplatin-based chemotherapy and catalase-induced tumor hypoxia relief together for combined chemo-radiotherapy with great synergistic efficacy, promising for clinical translation in cancer treatment. Copyright © 2017. Published by Elsevier Ltd.

  16. 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 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 < 0.001), but also maintained much longer drug retention time compared to the neutral PEGylated liposomes.

  17. Effect of liposomes on rheological and syringeability properties of hyaluronic acid hydrogels intended for local injection of drugs.

    Science.gov (United States)

    El Kechai, Naila; Bochot, Amélie; Huang, Nicolas; Nguyen, Yann; Ferrary, Evelyne; Agnely, Florence

    2015-06-20

    The aim of this work was to thoroughly study the effect of liposomes on the rheological and the syringeability properties of hyaluronic acid (HA) hydrogels intended for the local administration of drugs by injection. Whatever the characteristics of the liposomes added (neutral, positively or negatively charged, with a corona of polyethylene glycol chains, size), the viscosity and the elasticity of HA gels increased in a lipid concentration-dependent manner. Indeed, liposomes strengthened the network formed by HA chains due to their interactions with this polymer. The nature and the resulting effects of these interactions depended on liposome composition and concentration. The highest viscosity and elasticity were observed with liposomes covered by polyethylene glycol chains while neutral liposomes displayed the lowest effect. Despite their high viscosity at rest, all the formulations remained easily injectable through needles commonly used for local injections thanks to the shear-thinning behavior of HA gels. The present study demonstrates that rheological and syringeability tests are both necessary to elucidate the behavior of such systems during and post injection. In conclusion, HA liposomal gels appear to be a promising and versatile formulation platform for a wide range of applications in local drug delivery when an injection is required. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Stimuli-responsive liposome-nanoparticle assemblies.

    Science.gov (United States)

    Preiss, Matthew R; Bothun, Geoffrey D

    2011-08-01

    Nanoscale assemblies are needed that achieve multiple therapeutic objectives, including cellular targeting, imaging, diagnostics and drug delivery. These must exhibit high stability, bioavailability and biocompatibility, while maintaining or enhancing the inherent activity of the therapeutic cargo. Liposome-nanoparticle assemblies (LNAs) combine the demonstrated potential of liposome-based therapies, with functional nanoparticles. Specifically, LNAs can be used to concentrate and shield the nanoparticles and, in turn, stimuli-responsive nanoparticles that respond to external fields can be used to control liposomal release. The ability to design LNAs via nanoparticle encapsulation, decoration or bilayer-embedment offers a range of configurations with different structures and functions. This paper reviews the current state of research and understanding of the design, characterization and performance of LNAs. A brief overview is provided on liposomes and nanoparticles for therapeutic applications, followed by a discussion of the opportunities and challenges associated with combining the two in a single assembly to achieve controlled release via light or radiofrequency stimuli. LNAs offer a unique opportunity to combine the therapeutic properties of liposomes and nanoparticles. Liposomes act to concentrate small nanoparticles and shield nanoparticles from the immune system, while the nanoparticle can be used to initiate and control drug release when exposed to external stimuli. These properties provide a platform to achieve nanoparticle-controlled liposomal release. LNA design and application are still in infancy. Research concentrating on the relationships among LNA structure, function and performance is essential for the future clinical use of LNAs.

  19. Preparation and ocular pharmacokinetics of ganciclovir liposomes.

    Science.gov (United States)

    Shen, Yan; Tu, Jiasheng

    2007-12-07

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

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

    OpenAIRE

    Sandy Gim Ming Ong; Long Chiau Ming; Kah Seng Lee; Kah Hay Yuen

    2016-01-01

    The objective of the present study was to investigate the influence of the encapsulation efficiency and size of liposome on the oral bioavailability of griseofulvin-loaded liposomes. Griseofulvin-loaded liposomes with desired characteristics were prepared from pro-liposome using various techniques. To study the effect of encapsulation efficiency, three preparations of griseofulvin, namely, griseofulvin aqueous suspension and two griseofulvin-loaded liposomes with different amounts of griseofu...

  1. Tin compounds interaction with membranes of egg lecithin liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Man, D.; Podolak, M. [Opole Univ. (Poland). Inst. of Physics

    2007-05-15

    This work is a continuation of earlier research concerning the influence of tin compounds on the dynamic properties of liposome membranes produced with lecithin hen egg yolks (EYL). The experiments were carried out at room temperature (about 25 C). Four tin compounds were chosen, including three organic ones, (CH{sub 3}){sub 4}Sn, (C{sub 2}H{sub 5}){sub 4}Sn and (C{sub 3}H{sub 7}){sub 3}SnCl, and one inorganic, SnCl{sub 2}. The investigated compounds were admixed to water dispersions of liposomes. The content of the admixture changed within the range 0 mol-% to 11 mol-% in proportion to EYL. Two spin probes were used in the experiment: 2,2,6,6-tetramethylpiperidine- 1-oxyl (TEMPO) and 2-ethyl-2-(15-methoxy-15-oxopentadecyl)-4,4-dimethyl-3-oxazolidinyloxyl (16-DOXYL-stearic acid), which penetrated through different areas of the membrane. It was found that tin compounds containing chlorine were the most active in interaction with liposome membranes. In the case of (C{sub 3}H{sub 7}){sub 3}SnCl, after exceeding 4% admixture content, an additional line appeared in the spectrum of the TEMPO probe which can be a result of formation of domain structures in the membranes of the studied liposomes. Compounds containing chlorine are of ionized form in water solution. The obtained results can thus mean that the activity of admixtures can be seriously influenced by their ionic character. In case of an admixture of non-ionic compounds the compound with a longer hydrocarbon chain displayed a slightly stronger effect on the spectroscopic parameters of the probes. (orig.)

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

    Science.gov (United States)

    Patel, Niravkumar R.

    in increased cell association with these cancer cells. The 2C5-modified immunoliposomes, along with unmodified liposomes co-loaded with tariquidar and paclitaxel were tested for their antitumor effects in vivo. Significant tumor growth inhibition occurred with combination therapy in resistant as well as sensitive cell lines. However, immunoliposomes failed to increase antitumor effect in vivo as spontaneous accumulation of liposomes at added dose may have saturated tumor accumulation. We were also interested in evaluating physiological factors responsible for the MDR. Spheroids grown in vitro provided platform to demonstrate many characteristics of tumor tissues such as cell-cell interaction, a hypoxic core, low pH environment at core and a relevant genetic profile. In this study, spheroids were utilized to evaluate paclitaxel cytotoxity and to evaluate effects of 2C5 modification on cellular uptake. Lack of cytotoxicity was observed in spheroids treated with paclitaxel alone as well as in combination with tariquidar. Likely explanations could be the presence of cells in diverse cell cycle stages and limited penetration. Also, increased uptake was observed in spheroids when treated with 2C5-modified Rh-labeled liposomes compared to UPC10-modified Rh-labeled liposomes. Such results have clearly demonstrated the importance of using this novel research model in cancer research.

  3. 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.

  4. Targeted drug delivery using temperature-sensitive liposomes

    International Nuclear Information System (INIS)

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

    1984-01-01

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

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  6. Progress involving new techniques for liposome preparation

    Directory of Open Access Journals (Sweden)

    Zhenjun Huang

    2014-08-01

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

  7. 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......Liposomes are self-assembled phospholipid vesicles and have numerous research and therapeutic applications. In the pharmaceutical and biomedical sciences liposomes find use as models of biological membranes, partitioning medium and as drug carriers. The present review addresses the use of capillary...

  8. Spatial SPION Localization in Liposome Membranes

    OpenAIRE

    Bonnaud C{é}cile; Vanhecke Dimitri; Demurtas Davide; Rothen-Rutishauser Barbara M; Petri-Fink Alke

    2013-01-01

    Nanocarriers, including liposomes, offer great opportunities for targeted and controlled therapy. The development in this field has led to a large panel of drug delivery systems, which can be classified into 3 different nanovector generations. However, the success of such smart materials requires the control of a large variety of properties and parameters. Unfortunately, characterization at the nanoscale is often cumbersome and many methods are still being developed. Liposomes have been chara...

  9. Targeting of pegylated liposomal mitomycin-C prodrug to the folate receptor of cancer cells: Intracellular activation and enhanced cytotoxicity.

    Science.gov (United States)

    Patil, Yogita; Amitay, Yasmine; Ohana, Patricia; Shmeeda, Hilary; Gabizon, Alberto

    2016-03-10

    Mitomycin C (MMC) is a powerful anti-bacterial, anti-fungal and anti-tumor antibiotic, often active against multidrug resistant cells. Despite a broad spectrum of antitumor activity, MMC clinical use is relatively limited due to its fast clearance and dose-limiting toxicity. To exploit the potential antitumor activity of MMC and reduce its toxicity we have previously developed a formulation of pegylated liposomes with a lipophilic prodrug of MMC (PL-MLP), activated by endogenous reducing agents which are abundant in the tumor cell environment in the form of different thiols. PL-MLP has minimal in vitro cytotoxicity unless reducing agents are added to the cell culture to activate the prodrug. In the present study, we hypothesized that targeting PL-MLP via folate receptors will facilitate intracellular activation of prodrug and enhance cytotoxic activity without added reducing agents. We grafted a lipophilic folate conjugate (folate-PEG(5000)-DSPE) to formulate folate targeted liposomes (FT-PL-MLP) and examined in vitro cell uptake and cytotoxic activity in cancer cell lines with high folate receptors (HiFR). 3H-cholesterol-hexadecyl ether (3H-Chol)-radiolabeled liposomes were prepared to study liposome-cell binding in parallel to cellular uptake of prodrug MLP. 3H-Chol and MLP cell uptake levels were 4-fold and 9-fold greater in KB HiFR cells when FT-PL-MLP is compared to non-targeted PL-MLP liposomes. The cytotoxic activity of FT-PL-MLP liposomes was significantly increased up to ~5-fold compared with PL-MLP liposomes in all tested HiFR expressing cell lines. The enhanced uptake and intracytoplasmic liposome delivery was confirmed by confocal fluorescence studies with Rhodamine-labeled liposomes. In vivo, no significant differences in pharmacokinetics and biodistribution were observed when PL-MLP was compared to FT-PL-MLP by the intravenous route. However, when liposomes were directly injected into the peritoneal cavity of mice with malignant ascites of J6456 Hi

  10. Enzyme-induced shedding of a poly(amino acid)-coating triggers contents release from dioleoyl phosphatidylethanolamine liposomes.

    Science.gov (United States)

    Romberg, Birgit; Flesch, Frits M; Hennink, Wim E; Storm, Gert

    2008-05-01

    The enzymatically degradable poly(amino acid)-lipid conjugate poly(hydroxyethyl l-glutamine)-N-succinyl-dioctadecylamine (PHEG-DODASuc) has been shown to effectively prolong liposome circulation times. In this paper, we investigated whether PHEG-DODASuc can stabilize liposomes composed of the fusogenic, non-bilayer-forming lipid dioleoyl phosphatidylethanolamine (DOPE). Moreover, we evaluated the release of an entrapped compound after enzyme-induced shedding of the PHEG-coating, interbilayer contact and membrane destabilizing phase changes. Contents release was monitored using the fluorescent model compound calcein. Liposome destabilization and lipid mixing was studied by dynamic light scattering (DLS), fluorescence resonance energy transfer (FRET) and cryogenic-temperature transmission electron microscopy (cryo-TEM). It was shown that PHEG-DODASuc is able to stabilize DOPE-based liposomes and that contents release can be triggered by shedding of the PHEG-coating.

  11. Application of Coiled Coil Peptides in Liposomal Anticancer Drug Delivery Using a Zebrafish Xenograft Model.

    Science.gov (United States)

    Yang, Jian; Shimada, Yasuhito; Olsthoorn, René C L; Snaar-Jagalska, B Ewa; Spaink, Herman P; Kros, Alexander

    2016-08-23

    The complementary coiled coil forming peptides E4 [(EIAALEK)4] and K4 [(KIAALKE)4] are known to trigger liposomal membrane fusion when tethered to lipid vesicles in the form of lipopeptides. In this study, we examined whether these coiled coil forming peptides can be used for drug delivery applications. First, we prepared E4 peptide modified liposomes containing the far-red fluorescent dye TO-PRO-3 iodide (E4-Lipo-TP3) and confirmed that E4-liposomes could deliver TP3 into HeLa cells expressing K4 peptide on the membrane (HeLa-K) under cell culture conditions in a selective manner. Next, we prepared doxorubicin-containing E4-liposomes (E4-Lipo-DOX) and confirmed that E4-liposomes could also deliver DOX into HeLa-K cells. Moreover, E4-Lipo-DOX showed enhanced cytotoxicity toward HeLa-K cells compared to free doxorubicin. To prove the suitability of E4/K4 coiled coil formation for in vivo drug delivery, we injected E4-Lipo-TP3 or E4-Lipo-DOX into zebrafish xenografts of HeLa-K. As a result, E4-liposomes delivered TP3 to the implanted HeLa-K cells, and E4-Lipo-DOX could suppress cancer proliferation in the xenograft when compared to nontargeted conditions (i.e., zebrafish xenograft with free DOX injection). These data demonstrate that coiled coil formation enables drug selectivity and efficacy in vivo. It is envisaged that these findings are a step forward toward biorthogonal targeting systems as a tool for clinical drug delivery.

  12. Surface fractals in liposome aggregation.

    Science.gov (United States)

    Roldán-Vargas, Sándalo; Barnadas-Rodríguez, Ramon; Quesada-Pérez, Manuel; Estelrich, Joan; Callejas-Fernández, José

    2009-01-01

    In this work, the aggregation of charged liposomes induced by magnesium is investigated. Static and dynamic light scattering, Fourier-transform infrared spectroscopy, and cryotransmission electron microscopy are used as experimental techniques. In particular, multiple intracluster scattering is reduced to a negligible amount using a cross-correlation light scattering scheme. The analysis of the cluster structure, probed by means of static light scattering, reveals an evolution from surface fractals to mass fractals with increasing magnesium concentration. Cryotransmission electron microscopy micrographs of the aggregates are consistent with this interpretation. In addition, a comparative analysis of these results with those previously reported in the presence of calcium suggests that the different hydration energy between lipid vesicles when these divalent cations are present plays a fundamental role in the cluster morphology. This suggestion is also supported by infrared spectroscopy data. The kinetics of the aggregation processes is also analyzed through the time evolution of the mean diffusion coefficient of the aggregates.

  13. Doxorubicin-loaded photosensitive magnetic liposomes for multi-modal cancer therapy.

    Science.gov (United States)

    Shah, Saqlain A; Aslam Khan, M U; Arshad, M; Awan, S U; Hashmi, M U; Ahmad, N

    2016-12-01

    Multifunctional magnetic nanosystems have attracted an enormous attention of researchers for their potential applications in cancer diagnostics and therapy. The localized nanotherapies triggered by the external stimuli, like magnetic fields and visible light, are significant in clinical applications. We report a liposomal system that aims to treat cancer by magnetic hyperthermia, photodynamic therapy and chemotherapy simultaneously. The liposomes enclose clinically used photosensitizer m-THPC (Foscan) and anti-cancer drug doxorubicin, in its hydrophobic lipid bilayers, and contains magnetite nanoparticles in hydrophilic core. Three different sizes of magnetic nanoparticles (10, 22 and 30nm) and liposomes (40, 70 and 110nm) were used in this study. Magnetite single domain nanoparticles forming the magnetic core were superparamagnetic but liposomes expressed slight coercivity and hysteresis due to the clustering of nanoparticles in the core. This enhanced the heating efficiency (specific power loss) of the liposomes under an AC field (375kHz, 170Oe). Cell viability and toxicity were studied on HeLa cells using MTT assay and proteomic analysis. Confocal and fluorescence microscopy were used to study the photosensitizer's profile and cells response to combined therapy. It revealed that combined therapy almost completely eliminated the cancer cells as opposed to the separate treatments. Magnetic hyperthermia and photodynamic therapies were almost equally effective whereas chemotherapy showed the least effect. Copyright © 2016. Published by Elsevier B.V.

  14. Tumor Endothelial Cell-Specific Drug Delivery System Using Apelin-Conjugated Liposomes

    Science.gov (United States)

    Kawahara, Hiroki; Naito, Hisamichi; Takara, Kazuhiro; Wakabayashi, Taku; Kidoya, Hiroyasu; Takakura, Nobuyuki

    2013-01-01

    Background A drug delivery system specifically targeting endothelial cells (ECs) in tumors is required to prevent normal blood vessels from being damaged by angiogenesis inhibitors. The purpose of this study was to investigate whether apelin, a ligand for APJ expressed in ECs when angiogenesis is taking place, can be used for targeting drug delivery to ECs in tumors. Methods and Results Uptake of apelin via APJ stably expressed in NIH-3T3 cells was investigated using TAMRA (fluorescent probe)-conjugated apelin. Both long and short forms of apelin (apelin 36 and apelin 13) were taken up, the latter more effectively. To improve efficacy of apelin- liposome conjugates, we introduced cysteine, with its sulfhydryl group, to the C terminus of apelin 13, resulting in the generation of apelin 14. In turn, apelin 14 was conjugated to rhodamine-encapsulating liposomes and administered to tumor-bearing mice. In the tumor microenvironment, we confirmed that liposomes were incorporated into the cytoplasm of ECs. In contrast, apelin non-conjugated liposomes were rarely found in the cytoplasm of ECs. Moreover, non-specific uptake of apelin-conjugated liposomes was rarely detected in other normal organs. Conclusions ECs in normal organs express little APJ; however, upon hypoxic stimulation, such as in tumors, ECs start to express APJ. The present study suggests that apelin could represent a suitable tool to effectively deliver drugs specifically to ECs within tumors. PMID:23799018

  15. Tumor endothelial cell-specific drug delivery system using apelin-conjugated liposomes.

    Directory of Open Access Journals (Sweden)

    Hiroki Kawahara

    Full Text Available BACKGROUND: A drug delivery system specifically targeting endothelial cells (ECs in tumors is required to prevent normal blood vessels from being damaged by angiogenesis inhibitors. The purpose of this study was to investigate whether apelin, a ligand for APJ expressed in ECs when angiogenesis is taking place, can be used for targeting drug delivery to ECs in tumors. METHODS AND RESULTS: Uptake of apelin via APJ stably expressed in NIH-3T3 cells was investigated using TAMRA (fluorescent probe-conjugated apelin. Both long and short forms of apelin (apelin 36 and apelin 13 were taken up, the latter more effectively. To improve efficacy of apelin- liposome conjugates, we introduced cysteine, with its sulfhydryl group, to the C terminus of apelin 13, resulting in the generation of apelin 14. In turn, apelin 14 was conjugated to rhodamine-encapsulating liposomes and administered to tumor-bearing mice. In the tumor microenvironment, we confirmed that liposomes were incorporated into the cytoplasm of ECs. In contrast, apelin non-conjugated liposomes were rarely found in the cytoplasm of ECs. Moreover, non-specific uptake of apelin-conjugated liposomes was rarely detected in other normal organs. CONCLUSIONS: ECs in normal organs express little APJ; however, upon hypoxic stimulation, such as in tumors, ECs start to express APJ. The present study suggests that apelin could represent a suitable tool to effectively deliver drugs specifically to ECs within tumors.

  16. Engineering liposomal nanoparticles for targeted gene therapy.

    Science.gov (United States)

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

    2017-08-01

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

  17. 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.

  18. The role of phospholipid transfer protein in lipoprotein-mediated neutralization of the procoagulant effect of anionic liposomes.

    Science.gov (United States)

    Oslakovic, C; Jauhiainen, M; Ehnholm, C; Dahlbäck, B

    2010-04-01

    Serum has the ability to neutralize the procoagulant properties of anionic liposomes, with transfer of phospholipids (PLs) to both high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles. Phospholipid transfer protein (PLTP) mediates transfer of PLs between HDL and other lipoproteins and conversion of HDL into larger and smaller particles. To examine the role of PLTP in the neutralization of procoagulant liposomes. Procoagulant liposomes were incubated with different lipoproteins in the presence or absence of PLTP, and then tested for their ability to stimulate thrombin formation. In the absence of added PLTP, the lipoprotein-enriched fraction, total HDL, HDL(3) and very high-density lipoprotein (VHDL) were all able to neutralize the procoagulant properties of the liposomes. In these samples, endogenous PLTP was present, as judged by Western blotting. In contrast, no PLTP was present in LDL, HDL(2) and lipoprotein-deficient serum, all of which displayed no ability to neutralize the procoagulant liposomes. The phospholipid (PL) transfer activity was dependent on both enzyme (PLTP) and PL acceptor (lipoproteins). After treatment of the VHDL fraction with antiserum against PLTP, the neutralization of procoagulant activity was reduced, but could be regained by the addition of active PLTP. The neutralizing activity was dependent on a catalytically active form of PLTP, and addition of a low activity form of PLTP had no effect. In conclusion, PLTP was found to mediate transfer of anionic PLs to HDL and LDL, thereby neutralizing the effect of procoagulant liposomes, resulting in a reduction of procoagulant activity.

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

    Directory of Open Access Journals (Sweden)

    Chiong HS

    2013-03-01

    Full Text Available Hoe Siong Chiong,1 Yoke Keong Yong,1 Zuraini Ahmad,1 Mohd Roslan Sulaiman,1 Zainul Amiruddin Zakaria,1 Kah Hay Yuen,2 Muhammad Nazrul Hakim1,31Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia; 2School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor, Malaysia; 3Sports Academy, Universiti Putra Malaysia, Serdang, MalaysiaBackground: Liposomal drug delivery systems, a promising lipid-based nanoparticle technology, have been known to play significant roles in improving the safety and efficacy of an encapsulated drug.Methods: Liposomes, prepared using an optimized proliposome method, were used in the present work to encapsulate piroxicam, a widely prescribed nonsteroidal anti-inflammatory drug. The cytotoxic effects as well as the in vitro efficacy in regulation of inflammatory responses by free-form piroxicam and liposome-encapsulated piroxicam were evaluated using a lipopolysaccharide-sensitive macrophage cell line, RAW 264.7.Results: Cells treated with liposome-encapsulated piroxicam demonstrated higher cell viabilities than those treated with free-form piroxicam. In addition, the liposomal piroxicam formulation resulted in statistically stronger inhibition of pro-inflammatory mediators (ie, nitric oxide, tumor necrosis factor-α, interleukin-1β, and prostaglandin E2 than piroxicam at an equivalent dose. The liposome-encapsulated piroxicam also caused statistically significant production of interleukin-10, an anti-inflammatory cytokine.Conclusion: This study affirms the potential of a liposomal piroxicam formulation in reducing cytotoxicity and enhancing anti-inflammatory responses in vitro.Keywords: liposomes, nitric oxide, cytokines, prostaglandin E2, interleukin-1β, piroxicam

  20. A Case of Multiple Spontaneous Keloid Scars

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    Abdulhadi Jfri

    2015-07-01

    Full Text Available Keloid scars result from an abnormal healing response to cutaneous injury or inflammation that extends beyond the borders of the original wound. Spontaneous keloid scars forming in the absence of any previous trauma or surgical procedure are rare. Certain syndromes have been associated with this phenomenon, and few reports have discussed the evidence of single spontaneous keloid scar, which raises the question whether they are really spontaneous. Here, we present a 27-year-old mentally retarded single female with orbital hypertelorism, broad nasal bridge, repaired cleft lip and high-arched palate who presented with progressive multiple spontaneous keloid scars in different parts of her body which were confirmed histologically by the presence of typical keloidal collagen. This report supports the fact that keloid scars can appear spontaneously and are possibly linked to a genetic factor. Furthermore, it describes a new presentation of spontaneous keloid scars in the form of multiple large lesions in different sites of the body.

  1. Construction of spherical liposome on solid transducers for electrochemical DNA sensing and transfection.

    Science.gov (United States)

    Bhuvana, Mohanlal; Dharuman, Venkataraman

    2014-10-01

    Cationic 1,2-dioleoyl trimethyl ammonium propane (DOTAP) and neutral 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) are anchored on cysteamine (cyst), mercaptopropionic acid (MPA) monolayer (thiol monolayers) modified on an individual gold transducer. DOTAP and DOPE are mixed with gold nanoparticle (AuNP) to form spherical liposome-AuNP. The electrochemical behaviors of the surface attached DOTAP-AuNP and DOPE-AuNP in presence of [Fe(CN)6](3-/4-) depend on the method of layer formation. Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), and ultraviolet (UV)-visible spectroscopic techniques are used to characterize the liposome-AuNP nanocomposite. The studies indicate stability of spherical liposome-AuNP on the gold transducer. Label-free DNA hybridization detection on these surfaces reveals different detection limits. Confocal laser scanning microscopy (CLSM) is used to confirm the cell transfection.

  2. Interactions between macromolecule-bound antioxidants and Trolox during liposome autoxidation: A multivariate approach.

    Science.gov (United States)

    Çelik, Ecem Evrim; Rubio, Jose Manuel Amigo; Andersen, Mogens L; Gökmen, Vural

    2017-12-15

    The interactions between free and macromolecule-bound antioxidants were investigated in order to evaluate their combined effects on the antioxidant environment. Dietary fiber (DF), protein and lipid-bound antioxidants, obtained from whole wheat, soybean and olive oil products, respectively and Trolox were used for this purpose. Experimental studies were carried out in autoxidizing liposome medium by monitoring the development of fluorescent products formed by lipid oxidation. Chemometric methods were used both at experimental design and multivariate data analysis stages. Comparison of the simple addition effects of Trolox and bound antioxidants with measured values on lipid oxidation revealed synergetic interactions for DF and refined olive oil-bound antioxidants, and antagonistic interactions for protein and extra virgin olive oil-bound antioxidants with Trolox. A generalized version of logistic function was successfully used for modelling the oxidation curve of liposomes. Principal component analysis revealed two separate phases of liposome autoxidation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Formulation of a New Generation of Liposomes from Bacterial and ...

    African Journals Online (AJOL)

    AFM). Results: At 37 °C, the liposomes and archaeosomes interacted with cell membranes predominantly by fusion and endocytosis. The AFM images showed uniform and dispersed distribution of the liposomes. Conclusion: The findings ...

  4. Temoporfin-loaded liposomes: physicochemical characterization.

    Science.gov (United States)

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

    2010-07-11

    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 some problems associated with the commercial formulation Foscan where the drug is dissolved in a mixture of water-free ethanol and propylene glycol. The present study focuses on the physicochemical characterization of different liposome formulations with special emphasis on the influence of drug incorporation on the thermal phase behavior of the liposomes. In addition to conventional liposomes, pegylated lipids were used for the preparation of "stealth" liposomes. The dispersions as well as freeze-dried formulations were characterized by photon correlation spectroscopy, differential scanning calorimetry and cryo-electron microscopy. Incorporation of temoporfin resulted in a distinct concentration dependent decrease of the main phase transition of the liposomes. In case of liposomes based on dipalmitoylphosphatidylcholine/-glycerol, phase transition was close or even below body temperature. In contrast, if phospholipids with longer fatty acid chains (distearoylphosphatidylcholine/-glycerol) were used, phase transitions were well above body temperature even at high drug load. Size and thermal behavior were not distinctly influenced by the addition of pegylated lipids but cryo-electron microscopic 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. 2010 Elsevier B.V. All rights reserved.

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

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

  7. Synthesis of Ag-liposome nano composites.

    Science.gov (United States)

    Barani, Hossein; Montazer, Majid; Toliyat, Tayebeh; Samadi, Nasrin

    2010-12-01

    Silver nanoparticles were synthesized and stabilized by a simple, environment-friendly method in a liposomes structure. Liposomes were prepared by facing lecithin to the aqueous-phase solutions while stirring vigorously. The ratio of lecithin concentration to silver nitrate (K(Lec/Ag) = [Lecithin]/[AgNO(3)]) is the influencing factor in the synthesis of silver nanoparticles. The stability, size distribution, and antibacterial properties of synthesized silver nanoparticles were studied by ultraviolet (UV)-visible, dynamic light scattering, and antibacterial assay. The UV spectra indicated a single symmetric extinction peak at 400 nm, confirming the spherical shape of the synthesized silver nanoparticles. A high K(Lec/Ag) value leads to a reduction in the intensity of extinction spectra and increases the size of Ag-liposomes nanocomposites. The large Ag-liposomes nanocomposites are transformed to the smaller Ag-liposomes nanocomposites (from 342 to 190 nm) due to sonication treatment. The stabilized silver nanoparticles with various lecithin concentrations showed a good antibacterial activity against Staphylococcus aureus, a Gram-positive bacterium, and Escherichia coli, a Gram-negative bacterium.

  8. Treatment of Digital Ischemia with Liposomal Bupivacaine

    Directory of Open Access Journals (Sweden)

    José Raul Soberón

    2014-01-01

    Full Text Available Objective. This report describes a case in which the off-label use of liposomal bupivacaine (Exparel in a peripheral nerve block resulted in marked improvement of a patient’s vasoocclusive symptoms. The vasodilating and analgesic properties of liposomal bupivacaine in patients with ischemic symptoms are unknown, but our clinical experience suggests a role in the management of patients suffering from vasoocclusive disease. Case Report. A 45-year-old African American female was admitted to the hospital with severe digital ischemic pain. She was not a candidate for any vascular surgical or procedural interventions. Two continuous supraclavicular nerve blocks were placed with modest clinical improvement. These effects were also short-lived, with the benefits resolving after the discontinuation of the peripheral nerve blocks. She continued to report severe pain and was on multiple anticoagulant medications, so a decision was made to perform an axillary nerve block using liposomal bupivacaine (Exparel given the compressibility of the site as well as the superficial nature of the target structures. Conclusions. This case report describes the successful off-label usage of liposomal bupivacaine (Exparel in a patient with digital ischemia. Liposomal bupivacaine (Exparel is currently FDA approved only for wound infiltration use at this time.

  9. Adsorption of lecithin liposomes to acid clay.

    Science.gov (United States)

    Matsunaga, Naoki; Kato, An-Na; Murase, Norio

    2011-01-01

    The interaction between lecithin liposomes and acid clay was investigated to clarify the mechanism for liposome adsorption to the clay. It was found that the multilamellar vesicular structure of the liposomes was broken as a result of primary adsorption. The acid clay particles aggregated and were eventually covered by the lecithin layer structure. In the case of kaolin, on the other hand, the liposomes were weakly adsorbed to the clay and maintained the vesicular structure. The amount of primary adsorption to the clay surface, which was estimated from the adsorption isotherm, was more for acid clay than for kaolin, and the total amount adsorbed to the acid clay was also more than to kaolin. This result can be explained by the much higher density of the negative charge on the acid clay surface than that for kaolin. The liposomes are therefore considered to be adsorbed to the acid clay mainly by the choline positive charge residing at the end of the lecithin molecule, although this is of no net charge as a whole.

  10. Liposomal adjuvant development for leishmaniasis vaccines.

    Science.gov (United States)

    Askarizadeh, Anis; Jaafari, Mahmoud Reza; Khamesipour, Ali; Badiee, Ali

    2017-08-01

    Leishmaniasis is a parasitic disease that ranges in severity from skin lesions to fatality. Since long-lasting protection is induced upon recovery from cutaneous leishmaniasis, development of an effective vaccine is promising. However, there is no vaccine for use in humans yet. It seems limited efficacy in leishmaniasis vaccines is due to lack of an appropriate adjuvant or delivery system. Hence, the use of particulate adjuvants such as liposomes for effective delivery to the antigen presenting cells (APCs) is a valuable strategy to enhance leishmaniasis vaccine efficacy. The extraordinary versatility of liposomes because of their unique amphiphilic and biphasic nature allows for using antigens or immunostimulators within the core, on the surface or within the bilayer, and modulates both the magnitude and the T-helper bias of the immune response. In this review article, we attempt to summarize the role of liposomal adjuvants in the development of Leishmania vaccines and describe the main physicochemical properties of liposomes like phospholipid composition, surface charge, and particle size during formulation design. We also suggest potentially useful formulation strategies in order for future experiments to have a chance to succeed as liposomal vaccines against leishmaniasis.

  11. Liposome-encapsulated ISMN: a novel nitric oxide-based therapeutic agent against Staphylococcus aureus biofilms.

    Directory of Open Access Journals (Sweden)

    Camille Jardeleza

    Full Text Available Staphylococcus aureus in its biofilm form has been associated with recalcitrant chronic rhinosinusitis with significant resistance to conventional therapies. This study aims to determine if liposomal-encapsulation of a precursor of the naturally occurring antimicrobial nitric oxide (NO enhances its desired anti-biofilm effects against S. aureus, in the hope that improving its efficacy can provide an effective topical agent for future clinical use.S. aureus ATCC 25923 biofilms were grown in-vitro using the Minimum Biofilm Eradication Concentration (MBEC device and exposed to 3 and 60 mg/mL of the NO donor isosorbide mononitrate (ISMN encapsulated into different anionic liposomal formulations based on particle size (unilamellar ULV, multilamellar MLV and lipid content (5 and 25 mM at 24 h and 5 min exposure times. Biofilms were viewed using Live-Dead Baclight stain and confocal scanning laser microscopy and quantified using the software COMSTAT2.At 3 and 60 mg/mL, ISMN-ULV liposomes had comparable and significant anti-biofilm effects compared to untreated control at 24 h exposure (p = 0.012 and 0.02 respectively. ULV blanks also had significant anti-biofilm effects at both 24 h and 5 min exposure (p = 0.02 and 0.047 respectively. At 5 min exposure, 60 mg/mL ISMN-MLV liposomes appeared to have greater anti-biofilm effects compared to pure ISMN or ULV particles. Increasing liposomal lipid content improved the anti-biofilm efficacy of both MLV and ULVs at 5 min exposure.Liposome-encapsulated "nitric oxide" is highly effective in eradicating S. aureus biofilms in-vitro, giving great promise for use in the clinical setting to treat this burdensome infection. Further studies however are needed to assess its safety and efficacy in-vivo before clinical translation is attempted.

  12. Therapeutic Potential of Delivering Arsenic Trioxide into HPV-Infected Cervical Cancer Cells Using Liposomal Nanotechnology

    Science.gov (United States)

    Wang, Xiaoyan; Li, Dong; Ghali, Lucy; Xia, Ruidong; Munoz, Leonardo P.; Garelick, Hemda; Bell, Celia; Wen, Xuesong

    2016-02-01

    Arsenic trioxide (ATO) has been used successfully to treat acute promyelocytic leukaemia, and since this discovery, it has also been researched as a possible treatment for other haematological and solid cancers. Even though many positive results have been found in the laboratory, wider clinical use of ATO has been compromised by its toxicity at higher concentrations. The aim of this study was to explore an improved method for delivering ATO using liposomal nanotechnology to evaluate whether this could reduce drug toxicity and improve the efficacy of ATO in treating human papillomavirus (HPV)-associated cancers. HeLa, C33a, and human keratinocytes were exposed to 5 μm of ATO in both free and liposomal forms for 48 h. The stability of the prepared samples was tested using inductively coupled plasma optical emission spectrometer (ICP-OES) to measure the intracellular arsenic concentrations after treatment. Fluorescent double-immunocytochemical staining was carried out to evaluate the protein expression levels of HPV-E6 oncogene and caspase-3. Cell apoptosis was analysed by flow cytometry. Results showed that liposomal ATO was more effective than free ATO in reducing protein levels of HPV-E6 and inducing cell apoptosis in HeLa cells. Moreover, lower toxicity was observed when liposomal-delivered ATO was used. This could be explained by lower intracellular concentrations of arsenic. The slowly accumulated intracellular ATO through liposomal delivery might act as a reservoir which releases ATO gradually to maintain its anti-HPV effects. To conclude, liposome-delivered ATO could protect cells from the direct toxic effects induced by higher concentrations of intracellular ATO. Different pathways may be involved in this process, depending on local architecture of the tissues and HPV status.

  13. Advanced strategies in liposomal cancer therapy

    DEFF Research Database (Denmark)

    Andresen, Thomas Lars; Jensen, Simon Skøde; Jørgensen, Kent

    2005-01-01

    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...... have emerged ranging from externally triggered light- and thermo-sensitive liposomes to receptor targeted, pH- and enzymatically triggered liposomes relying on an endogenous trigger mechanism in the cancerous tissue. However, even though several of these strategies were introduced three decades ago......, 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...

  14. Liposomal cancer therapy: exploiting tumor characteristics

    DEFF Research Database (Denmark)

    Kaasgaard, Thomas; Andresen, Thomas Lars

    2010-01-01

    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......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...

  15. 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.

  16. Inhibition of HIV Virus by Neutralizing Vhh Attached to Dual Functional Liposomes Encapsulating Dapivirine

    Science.gov (United States)

    Wang, Scarlet Xiaoyan; Michiels, Johan; Ariën, Kevin K.; New, Roger; Vanham, Guido; Roitt, Ivan

    2016-07-01

    Although highly active antiretroviral therapy (HAART) has greatly improved the life expectancy of HIV/AIDS patients, the treatment is not curative. It is a global challenge which fosters an urgent need to develop an effective drug or neutralizing antibody delivery approach for the prevention and treatment of this disease. Due to the low density of envelope spikes with restricted mobility present on the surface of HIV virus, which limit the antibody potency and allow virus mutation and escape from the immune system, it is important for a neutralizing antibody to form bivalent or multivalent bonds with the virus. Liposome constructs could fulfil this need due to the flexible mobility of the membrane with its attached antibodies and the capacity for drug encapsulation. In this study, we evaluated the neutralization activity of a range of liposome formulations in different sizes coated with anti-gp120 llama antibody fragments (Vhhs) conjugated via either non-covalent metal chelation or a covalent linkage. The non-covalent construct demonstrated identical binding affinity to HIV-1 envelope glycoprotein gp120 and neutralizing ability for HIV virus as free Vhh. Although covalently linked Vhh showed significant binding affinity to gp120, it unexpectedly had a lower neutralization potency. This may be due to the comparability in size of the viral and liposome particles restricting the number which can be bound to the liposome surface so involving only a fraction of the antibodies, whereas non-covalently attached antibodies dissociate from the surface after acting with gp120 and free the remainder to bind further viruses. Covalently conjugated Vhh might also trigger the cellular uptake of a liposome-virion complex. To explore the possible ability of the antibody-coated liposomes to have a further function, we encapsulated the hydrophobic antiviral drug dapivirine into both of the non-covalently and covalently conjugated liposome formulations, both of which revealed high

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

    Science.gov (United States)

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

    2012-01-01

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

  18. Potential Effect of Liposomes and Liposome-Encapsulated Botulinum Toxin and Tacrolimus in the Treatment of Bladder Dysfunction

    Directory of Open Access Journals (Sweden)

    Joseph J. Janicki

    2016-03-01

    Full Text Available Bladder drug delivery via catheter instillation is a widely used treatment for recurrence of superficial bladder cancer. Intravesical instillation of liposomal botulinum toxin has recently shown promise in the treatment of overactive bladder and interstitial cystitis/bladder pain syndrome, and studies of liposomal tacrolimus instillations show promise in the treatment of hemorrhagic cystitis. Liposomes are lipid vesicles composed of phospholipid bilayers surrounding an aqueous core that can encapsulate hydrophilic and hydrophobic drug molecules to be delivered to cells via endocytosis. This review will present new developments on instillations of liposomes and liposome-encapsulated drugs into the urinary bladder for treating lower urinary tract dysfunction.

  19. Efficacy of neutral and negatively charged liposome-loaded gentamicin on planktonic bacteria and biofilm communities

    Directory of Open Access Journals (Sweden)

    Alhariri M

    2017-09-01

    Full Text Available Moayad Alhariri,1 Majed A Majrashi,2 Ali H Bahkali,3 Faisal S Almajed,4 Ali O Azghani,5 Mohammad A Khiyami,2 Essam J Alyamani,2 Sameera M Aljohani,6 Majed A Halwani1 1Nanomedicine Department, King Abdullah International Medical Research Center (KAIMRC, King Saud bin Abdulaziz University for Health Sciences, 2National Centre for Biotechnology, Life Sciences and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST, 3Botany and Microbiology Department, College of Science, King Saud University, 4Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; 5Department of Biology, The University of Texas at Tyler, Tyler, TX, USA; 6College of Science and Health Professions, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia Abstract: We investigated the efficacy of liposomal gentamicin formulations of different surface charges against Pseudomonas aeruginosa and Klebsiella oxytoca. The liposomal gentamicin formulations were prepared by the dehydration–rehydration method, and their sizes and zeta potential were measured. Gentamicin encapsulation efficiency inside the liposomal formulations was determined by microbiologic assay, and stability of the formulations in biologic fluid was evaluated for a period of 48 h. The minimum inhibitory concentration and the minimum bactericidal concentration were determined, and the in vitro time kill studies of the free form of gentamicin and liposomal gentamicin formulations were performed. The activities of liposomal gentamicin in preventing and reducing biofilm-forming P. aeruginosa and K. oxytoca were compared to those of free antibiotic. The sizes of the liposomal formulations ranged from 625 to 806.6 nm in diameter, with the zeta potential ranging from

  20. Characterization and cytotoxicity of mixed polyethyleneglycol modified liposomes containing doxorubicin.

    Science.gov (United States)

    Sadzuka, Yasuyuki; Sugiyama, Ikumi; Tsuruda, Tomoko; Sonobe, Takashi

    2006-04-07

    Liposomes are recognized as one of the useful drug carriers, but have many problems to overcome before their clinical application. Liposomes, bonding peculiarly with serum protein (opsonization), are taken up by reticuloendothelial system (RES) cells in the liver and spleen. It is known that polyethyleneglycol (PEG) modification of the liposome surface induces the formation of a fixed aqueous layer around the liposomes due to the interaction between the PEG-polymer and water molecule, and thus prevents the attraction of opsonins. Namely, PEG-modified liposomes are able to escape trapping by the RES cells, and have a prolonged circulation time. In this study, the effects of different anchors with the same PEG molecular weight on the cell uptake and cytotoxicity of mixed PEG-modified liposomal doxorubicin (DOX) were examined. The fixed aqueous layer thickness (FALT) of liposomes covered with mixtures of PEG-molecules which differ in their chain length were increased, compared to that of the single PEG2000-modified liposome. Mixed PEG-modification of liposomes with different anchors (PEG2000-(1-monomethoxypolyethyleneglycol-2,3-distearoylglycerol (DSG): cholesterol (CHO)=1:1)-modified liposome) led to an increase in the FALT, compared to that of each single PEG-modification. The uptake of DOX into Ehrlich ascites carcinoma cells by the liposomes covered with PEG-CHO was higher than the other liposomes. Thus, liposomes covered with PEG-DSG and PEG-CHO have an enhanced cytotoxicity. In conclusion, it was confirmed that mix-modified liposomes using PEG-lipid with different anchors were superior.

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

    Science.gov (United States)

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

    2016-03-15

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

  2. Development and optimization of a new processing approach for manufacturing topical liposomes-in-hydrogel drug formulations by dual asymmetric centrifugation.

    Science.gov (United States)

    Ingebrigtsen, Sveinung G; Škalko-Basnet, Nataša; Holsæter, Ann Mari

    2016-09-01

    The objective of the present study was to utilize dual asymmetric centrifugation (DAC) as a novel processing approach for the production of liposomes-in-hydrogel formulations. Lipid films of phosphatidylcholine, with and without chloramphenicol (CAM), were hydrated and homogenized by DAC to produce liposomes in the form of vesicular phospholipid gels with a diameter in the size range of 200-300 nm suitable for drug delivery to the skin. Different homogenization processing parameters were investigated along with the effect of adding propylene glycol (PG) to the formulations prior to homogenization. The produced liposomes were incorporated into a hydrogel made of 2.5% (v/v) soluble β-1,3/1,6-glucan (SBG) and mixed by DAC to achieve a homogenous liposomes-in-hydrogel-formulation suitable for topical application. CAM-containing liposomes with a vesicle diameter of 282 ± 30 nm and polydispersity index (PI) of 0.13 ± 0.02 were successfully produced by DAC after 50 min centrifugation at 3500 rpm, and homogenously (centrifugation time to 2 min and 55 s, producing liposomes of 230 ± 51 nm and PI of 0.25 ± 0.04. All formulations had an entrapment efficiency of approximately 50%. We managed to develop a relatively fast and reproducible new method for the production of liposomes-in-hydrogel formulations by DAC.

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

    Directory of Open Access Journals (Sweden)

    Samadikhah HR

    2011-10-01

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

  4. Near-infrared spectroscopic studies of self-forming lipids and nanovesicles

    Science.gov (United States)

    Bista, Rajan K.; Bruch, Reinhard F.

    2009-02-01

    Lipids and liposomes have remained an active research topic for several decades due to their significance as membrane model. Several vibrational spectroscopic techniques have been developed and employed to study the properties of lipids and liposomes. In this study, near-infrared (NIR) spectroscopy has been used to analyze a suite of synthesized PEGylated lipids trademarked as QuSomesTM. The three amphiphiles used in this study, differ in their apolar hydrophobic chain length and contain various units of polar polyethylene glycol (PEG) head groups. In contrast to conventional phospholipids, this new kind of lipids forms liposomes spontaneously upon hydration, without the supply of external activation energy. Whilst the NIR spectra of QuSomesTM show a common pattern, differences in the spectra are observed which enable the lipids to be distinguished. NIR absorption spectra of these new artificial lipids have been recorded in the spectral range of 4800-9000 cm-1 (~2100-1100 nm) by using a new miniaturized spectrometer based on micro-optical-electro-mechanical systems (MOEMS) technology. In particular, we have established specific band structures as "molecular fingerprints" corresponding to overtones and combinations vibrational modes involving mainly C-H and O-H functional groups for sample analysis of QuSomesTM. Moreover, we have demonstrated that the nanovesicles formed by such lipids in polar solvents show high stability and obey Beer's law at low concentration. The results reported in this study may find applications in various field including the development of lipids based drug delivery systems.

  5. Spontaneous pneumothorax in weightlifters.

    Science.gov (United States)

    Marnejon, T; Sarac, S; Cropp, A J

    1995-06-01

    Spontaneous pneumothorax is infrequently caused by strenuous exertion. To our knowledge there has only been one case of spontaneous pneumothorax associated with weightlifting reported in the medical literature. We describe three consecutive cases of spontaneous pneumothorax associated with weightlifting. We postulate that spontaneous pneumothorax in these patients may be secondary to improper breathing techniques. It is important that physicians and weight trainers be aware of the association between weight lifting and spontaneous pneumothorax and assure that proper instruction is given to athletes who work with weights.

  6. F. VON HAYEK’S THEORY OF SPONTANEOUS ORDER

    Directory of Open Access Journals (Sweden)

    О. Nesterenko

    2013-04-01

    Full Text Available The essence and the genesis of spontaneous order are disclosed in the context of critical analysis of constructivism. The author’s approach to the definition of the characteristic features of the spontaneous order is proposed. The dichotomy of the order is revealed towards the economic sphere in form of spontaneous order and organization.

  7. DISSOLUTION CHARACTERISTIC OF CHLORAMPHENICOL PALMITATE-LIPOSOMAL PREPARATION

    Directory of Open Access Journals (Sweden)

    Morteza Rafiee-Tehrani

    1990-07-01

    Full Text Available Solid dispersions of chloramphenicol palmitate and dipalmitoyl-phosphatidylcholine (lecithin have been produced both as copreci-pitate and physical mixtures. The dissolution behavior of both forms were compared with pure chloramphenicol palrnitate st different weight ratios of chloramphenicol palrnitate-lecithin (liposomal system; as well as various pH. The dissolution characteristic of physical mixtures for different weight ratios of chloramphenicol palmitate-lecithin was similar to the pure drug. Whereas, the coprecipitates produced a 2.8 fold greater initial dissolution rate (1DR and a 2.4 fold greater drug release concentration after 60 min at a chloramphenicol palmitatc-lecithin weight ratio of 19:1. However, lecithin content enhancement to 9:1, 4:1 and 1.5:1 compositions, resulted in a further increase of 6%, 21%. and 24%. respectively in the initial dissolution rate. In¬creasing the lecithin content shows only a slight increase (8.5°c on drug release after 60 min when, the chloramphenicol palrnitate lecithin weight ratio was 1.5:1. However, other weight ratios did not show any effect on the improvement of drug release after 60 min. I he effect of pH of the medium on dissolution was slight, but varied with composition of the system."nIn conclusion, liposome encapsulation of chloramphenicol palmitale has a significant effect on dissolution improvement of this drug.

  8. 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.

  9. Designing of 14C, 3H-labeled liposomal preparations and their distribution in inner organs of experimental animals

    International Nuclear Information System (INIS)

    Isaev, E.I.; Kamalova, M.E.; Isakova, A.V.; Mirakhmedov, F.K.; Saatov, T.S.

    2004-01-01

    Full text: Development of methods for introduction of drug liposomal forms into practice is an urgent task for medicine and radiobiology. Per oral way of administration of the medications has been unexplored properly yet. Preservation of their stability in the gastro-intestinal tract is the essential requirement to the liposomes. Literature data and our studies showed that the elevated saturation of fatty acids and viscosity of liposomal membrane bilayer increases their stability to acidic and alkaline media of the digestive system. To prepare the liposome we used 14C,H-labeled lipids isolated from tissues by means of preparative chromatography after administration of D(1-614C)glucose (specific radioactivity 100 mkCu/mM) as well as of D(1-3H)-galactose (specific radioactivity 900 mkCU/mM) to 10 rats. Organ-specific liposomes were prepared in accordance with the special method without ultrasound processing to administered them with milk per orally to rats by means of a gastric probe. Before administration of 14C,3H liposomes the animals were not fed for 16-20 hours for complete emptying of the gastrointestinal tract. Under these conditions 1-1.5 hours after administration of liposomes their maximum amount was absorbed from he intestine. We found tissue specificity of the liposome administered. If the amount of administered liposomes for each tissue to be taken for 100%, in target organs their distribution (in %) would be as follows: 0.30/0.39 in the heart, 0.54/0.06 in the skeletal muscle, 0.4/0.6 in the brain, 4.2/10.2 in the spleen, 2.9/6.1 in the pancreas, 5.1/1.2 in the kidney. In these experiments liposomes had covering of 14 C, 3 H-glycosphingolipids of the spleen. Under these conditions 3H-cAMP in the form of liposomes was administered to mice per orally to measure radioactivity (in cpm 100mg of tissue) in the organs. The values were as follows: 77±6.3 in the liver, 750±47 in the spleen, 250±19 in the kidney, 70±77 in the heart, 267±21 in the lung and 95

  10. Modulation of pharmacokinetic behavior of liposomes

    NARCIS (Netherlands)

    Scherphof, G.L.; Velinova, M.; Kamps, J.; Donga, J.; Want, H. van der; Kuipers, F.; Havekes, L.; Daemen, T.

    1997-01-01

    The authors's recent work on matters pertinent to the in vivo processing of systemically administered liposomes is reviewed. particular emphasis is given to factors influencing blood clearance rates, hepatic and splenic uptake and intrahepatic as well as intrasplenic distribution. In addition to

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

    African Journals Online (AJOL)

    Background: Radix Astragali was one of the main compositions of 'Modified Danggui Buxue Decoction' used for treatment of various kidney diseases. Astragaloside IV was the active composition of Radix Astragali. Astragaloside IV liposomes were used for the treatment of adriamycin-induced nephropathy (AN) rats.

  12. Herbal liposome for the topical delivery of ketoconazole for the effective treatment of seborrheic dermatitis

    Science.gov (United States)

    Dave, Vivek; Sharma, Swati; Yadav, Renu Bala; Agarwal, Udita

    2017-11-01

    The aim of the present study was to develop liposomal gel containing ketoconazole and neem extract for the treatment of seborrheic dermatitis in an effectual means. Azoles derivatives that are commonly used to prevent superficial fungal infections include triazole category like itraconazole. These drugs are available in the form of oral dosage that required a long period of time for treatment. Ketoconazole is available in the form of gel but is not used with any herbal extract. Neem ( Azadirachta indica) leaves show a good anti-bacterial and anti-fungal activity and have great potential as a bioactive compound. The thin film hydration method was used to design an herbal liposomal preparation. The formulation was further subjected to their characterization as particle size, zeta potential, entrapment efficiency, % cumulative drug release, and anti-fungal activity and it was also characterized by the mean of their physicochemical properties such as FTIR, SEM, DSC, TGA, and AFM. The results show that the formulation of liposomes with neem extract F12 were found to be optimum on the basis of entrapment efficiency in the range 88.9 ± 0.7%, with a desired mean particle size distribution of 141.6 nm and zeta potential - 45 mV. The anti-fungal activity of liposomal formulation F12 was carried out against Aspergillus niger and Candida tropicalis by measuring the inhibition zone 8.9 and 10.2 mm, respectively. Stability of optimized formulation was best seen at refrigerated condition. Overall, these results indicated that developed liposomal gel of ketoconazole with neem extract could have great potential for seborrheic dermatitis and showed synergetic effect for the treatment.

  13. Drug release from liposome coated hydrogels for soft contact lenses: the blinking and temperature effect.

    Science.gov (United States)

    Paradiso, P; Colaço, R; Mata, J L G; Krastev, R; Saramago, B; Serro, A P

    2017-10-01

    In this article, liposome-based coatings aiming to control drug release from therapeutic soft contact lenses (SCLs) materials are analyzed. A PHEMA based hydrogel material loaded with levofloxacin is used as model system for this research. The coatings are formed by polyelectrolyte layers containing liposomes of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and DMPC + cholesterol (DMPC + CHOL). The effect of friction and temperature on the drug release is investigated. The aim of the friction tests is to simulate the blinking of the eyelid in order to verify if the SCLs materials coated with liposomes are able to keep their properties, in particular the drug release ability. It was observed that under the study conditions, friction did not affect significantly the drug release from the liposome coated PHEMA material. In contrast, increasing the temperature of release leads to an increase of the drug diffusion rate through the hydrogel. This phenomenon is recorded both in the control and in the coated samples. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1799-1807, 2017. © 2016 Wiley Periodicals, Inc.

  14. Spectroscopic and morphological studies on interaction between gold nanoparticle and liposome constructed with phosphatidylcholine

    Science.gov (United States)

    Tsukada, C.; Tsuji, T.; Matsuo, K.; Nomoto, T.; Kutluk, G.; Sawada, M.; Ogawa, S.; Yoshida, T.; Yagi, S.

    2015-03-01

    The gold nanoparticles (Au NPs) colloidal solution and the phosphatidylcholine (PC) liposome aqueous solution are fabricated by the solution plasma method and the extrusion procedure, respectively. When the Au NPs colloidal solution and the PC liposome aqueous solution are mixed, considering the TEM image, we think that the Au NPs firstly are covered with the PC molecules, which do not contribute to form the PC liposome, and subsequently the Au NPs covered with the PC adsorb on the PC liposome surface. We propose that the PC molecule adsorbs on the Au sheet surface at the methyl group of N-CH3 and the oxygen atoms of P-O, P=O, C-O and C=O bonds, because each peak intensity of N, O and P K-edges NEXAFS spectra for the PC/Au sheet is reduced in comparison with that for the PC multilayer. Furthermore, the Au NPs covered with PC seem to be aggregated each other through the hydrophobic groups of PC on Au NPs.

  15. Engineering of (10-hydroxycamptothecin intercalated layered double hydroxide)@liposome nanocomposites with excellent water dispersity

    Science.gov (United States)

    Zhang, Yongfang; Wu, Xiaowen; Mi, Yuwei; Li, Haiping; Hou, Wanguo

    2017-09-01

    A hierarchical nanocomposite of 10-hydroxycamptothecin (HCPT), a nonionic and lipophilic anticancer drug, intercalated layered double hydroxide (LDH) encapsulated in liposomes was constructed. HCPT molecules were first incorporated into sodium cholate (Ch) micelles, and the resultant negatively charged HCPT-loaded Ch micelles were then co-assembled with positively charged LDH single-layer nanosheets, forming a HCPT/Ch intercalated LDH (HCPT-Ch-LDH) host-gest nanohybrid. The nanohybrid particles were further coated with liposomes (LSs), gaining a core-shell nanocomposite, denoted as (HCPT-Ch-LDH)@LS. The so-obtained samples were characterized using TEM, SAXS, FT-IR, DLS, and elemental analyses. Special emphasis was placed on the effect of liposome-coating for the HCPT-Ch-LDH on its water dispersity and drug-release. The results showed that the nanocomposite has excellent water dispersity and enhanced drug sustained-release performance in comparison with the HCPT-Ch-LDH, demonstrating that the liposome-coating for drug-LDH nanohybrids is an effective strategy to enhance their water dispersity and sustained-release performances. This work provides an effective strategy for engineering of LDH-based delivery systems for nonionic and lipophilic drugs.

  16. Comparison of therapeutic effects of liposomal Tranexamic Acid and conventional Hydroquinone on melasma.

    Science.gov (United States)

    Banihashemi, Mahnaz; Zabolinejad, Naghmeh; Jaafari, Mahmoud Reza; Salehi, Maryam; Jabari, Asma

    2015-09-01

    Melasma is one of the most common cosmetic disorders with skin darkening. Although several treatment modalities are available, none is satisfactorily used in management of this condition. Tranexamic acid (TA), a plasmin inhibitor, is reported to improve melasma when injected locally or used as oral and topical forms. The aim of this study was to compare therapeutic effects of liposomal tranexamic acid and conventional hydroquinone on melasma. Thirty women with bilateral melasma were enrolled in a split-face trial lasting 12 weeks. Patients blindly applied 5% topical liposomal TA and 4% hydroquinone cream, to the designated sides of the face twice daily in addition to the assigned sunscreen in the morning. Skin pigmentation was measured using MASI (Melasma Area and Severity Index) at each visit separately for each side at the base line and every month until one month after treatment course. Data were obtained from patients file and were analyzed statistically using SPSS software, paired samples t-test, and repeated measured ANOVA. Twenty-three patients completed the study. The mean MASI scores significantly reduced in both treated sides (P < P = 0.001) after 12 week. A greater decrease was observed with 5% liposomal TA, although this difference was not statistically significant. Irritation occurred in three patients with hydroquinone, while no serious adverse events occurred with TA. On the basis of these results, topical liposomal TA can be used as a new, effective, safe, and promising therapeutic agent in melasma. © 2015 Wiley Periodicals, Inc.

  17. Spectroscopic Study of the Interaction of Carboxyl-Modified Gold Nanoparticles with Liposomes of Different Chain Lengths and Controlled Drug Release by Layer-by-Layer Technology.

    Science.gov (United States)

    Kanwa, Nishu; De, Soumya Kanti; Adhikari, Chandan; Chakraborty, Anjan

    2017-12-21

    In this article, we investigate the interactions of carboxyl-modified gold nanoparticles (AuC) with zwitterionic phospholipid liposomes of different chain lengths using a well-known membrane probe PRODAN by steady-state and time-resolved spectroscopy. We use three zwitterionic lipids, namely, dipalmitoylphosphatidylcholine (DPPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC), which are widely different in their phase transition temperatures to form liposome-AuC assemblies. The steady-state and time-resolved studies indicate that the AuC brings in stability toward liposomes by local gelation. We observe that the bound AuC detach from the surface of the liposomes under pH ≈ 5 due to protonation of the carboxyl group, thus eliminating the electrostatic interaction between nanoparticles and head groups of liposomes. The detachment rate of AuC from the liposome-AuC assemblies is different for the aforementioned liposomes due to differences in their fluidity. We exploited the phenomena for the controlled release of a prominent anticancer drug Doxorubicin (DOX) under acidic conditions for different zwitterionic liposomes. The drug release rate was further optimized by coating of liposome-AuC assemblies with oppositely charged polymer (P), polydiallyldimethylammonium chloride, followed by a mixture of lipids L (DMPC:DMPG) and again with a polymer in a layer-by-layer fashion to obtain capsule-like structures. This system is highly stable for weeks, as confirmed by field-emission scanning electron microscopy (FE-SEM) and confocal laser scanning microscopy (CLSM) imaging, and inhibits premature release. The layer coating was confirmed by hydrodynamic size and zeta potential measurements of the systems. The capsules obtained are of immense importance as they can control release of the drug from the systems to a large extent.

  18. Allometric scaling of pegylated liposomal anticancer drugs.

    Science.gov (United States)

    Caron, Whitney P; Clewell, Harvey; Dedrick, Robert; Ramanathan, Ramesh K; Davis, Whitney L; Yu, Ning; Tonda, Margaret; Schellens, Jan H; Beijnen, Jos H; Zamboni, William C

    2011-10-01

    Pegylated liposomal formulations contain lipid conjugated to polyethylene glycol. The disposition of encapsulated drug is dictated by the composition of the liposome, thus altering the pharmacokinetic (PK) profile of the drug. Allometric scaling is based on a power-log relationship between body weight (W) and drug clearance (CL) among mammals and has been used to compare the disposition of nonliposomal drugs across species. The objectives of this study were to use allometric scaling to: (1) compare the disposition of pegylated liposomal drugs across speciesand determine the best scaling model and (2) predict PK parameters of pegylated liposomal drugs in humans. The PK of pegylated liposomal CKD-602 (S-CKD602), doxorubicin (Doxil®), and cisplatin (SPI-077) were compared. PK studies ofS-CKD602, Doxil®, and SPI-077 were performed at the maximum tolerated dose (MTD) in male and female mice, rats, dogs and patients with refractory solid tumors. The allometric equation used to evaluate the relationship between W and CL in each species was CL = a(W)(m) (a = empirical coefficient; m = allometric exponent). Substitution of physiological variables other than body weight, such as factors representative of the mononuclear phagocyte system (MPS) were evaluated. Dedrick Plots and Maximum Life-Span Potential (MLP) were used to determine scaling feasibility. Standard allometry demonstrated a relationship between clearance of S-CKD602, Doxil®, and SPI-077 and body, spleen, liver, and kidney weights, total monocyte count, and spleen and liver blood flow. However, using scaling to predict CL of these agents in humans often resulted in differences >30%. Despite a strong correlation between body weight and MPS-associated variables with CL among preclinical species, the use of the equations did not predict CL. Thus, new methods of allometric scaling and measures of MPS function need to be developed.

  19. Biodistribution and pharmacokinetics of In-111-labeled Stealth{reg_sign} liposomes in patients with solid tumours

    Energy Technology Data Exchange (ETDEWEB)

    Harrington, K.J.; Peters, A.M.; Mohammadtaghi, S. [Hammersmith Hospital, London (United Kingdom)] [and others

    1996-05-01

    The use of liposomal doxorubicin yields response rates of up to 70-80% in patients with AIDS-related Kaposi`s sarcoma with favourable alteration of the toxicity profile of the drug. Liposomal delivery of therapy in patients with solid cancers is currently under investigation. Our aim is to determine the biodistribution and pharmacokinetics of In-111-labeled Stealth{reg_sign} liposomes (SEQUUS{trademark}) liposomes (SEQUUS{trademark} Pharmaceuticals Inc., Menlo Park, USA) in patients with advanced solid malignant tumours. Ten patients (4 male, 6 female) with a median age of 59 (range 43 - 75) received 100 MBq of In-111-labeled Stealth{reg_sign} liposomes. Four had breast cancer, 3 head and neck tumours, 2 lung and 1 cervical cancer. Blood samples and whole body gamma camera images were obtained at 0.5, 4, 24, 48, 72, 96 and 240 hours after injection and sequential 24 hour urine collections were performed for the first 96 h. SPECT imaging was performed when indicated. High definition images of tumours were obtained in 9 patients (3/4 breast, 3/3 head and neck, 2/2 lung and 1/1 cervix cancers). One patient (breast cancer) had negative images. The median cumulative urinary excretion of In-111 over the first 96 h was 17.8 (range 3.5-21.3) % of the injected dose. The uptake of liposomes in various tissues was estimated from regions of interest on the whole body images. Prominent uptake was seen in the liver (10-15% of injected dose), lungs (4-9%) and spleen (2-8%). Tumour uptake in the first 96 h varied form 0.5-4% of the injected dose. This is approximately 10 fold higher than might be expected from experience with other targeting methods (eg monoclonal antibodies). These data confirm that Stealth liposomes have a prolonged circulation half-life and localise to solid tumour tissue.

  20. 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.

  1. OPTIMIZATION OF MIXING TEMPERATURE AND SONICATION DURATION IN LIPOSOME PREPARATION

    Directory of Open Access Journals (Sweden)

    Dina Christin Ayuning Putri

    2017-11-01

    Full Text Available Liposomes are a delivery system used in pharmaceutical products and cosmetics. Liposomes have many advantages such as increase stability and efficacy, can be targeted to reduce toxicity and increase accumulation at the target site and are biocompatible.  Preparation of liposomes can be done by conventional or new methods which are still being developed. Conventional methods often require a long time and organic solvents which may be toxic. Heating (Mozafari method is one of the new methods developed in the manufacture of liposomes without organic solvents. Mixing temperature can affect the physical properties of liposomes. The particle size has become one of the important physical properties because it affects the absorption of the drug. Sonication is an easy method of choice in reducing the size of liposomes. Optimization of mixing temperature and duration of sonication in liposomes’ preparation using new heating methods and sonication were performed by factorial design with 2 factors and 3-levels to obtain optimal liposome size. Data were analyzed with two-way ANOVA. The results showed that both mixing temperature and sonication duration significantly affect liposome size, but the interaction was not statistically significant. Data analysis also showed that mixing temperature, sonication, and their interaction do not affect the polydispersity index of liposome. Results showed the optimum mixing temperature and sonication duration that can produce liposomes with size below 100 nm is at 60°C for 30 minutes.

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

    Directory of Open Access Journals (Sweden)

    Frieder Helm

    2015-04-01

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

  3. 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.

  4. Cysteines introduced into extracellular loops 1 and 4 of human P-glycoprotein that are close only in the open conformation spontaneously form a disulfide bond that inhibits drug efflux and ATPase activity.

    Science.gov (United States)

    Loo, Tip W; Clarke, David M

    2014-09-05

    P-glycoprotein (P-gp) is an ATP-binding cassette drug pump that protects us from toxic compounds and confers multidrug resistance. The protein is organized into two halves. The halves contain a transmembrane domain (TMD) with six transmembrane segments and a nucleotide-binding domain (NBD). The drug- and ATP-binding sites reside at the TMD1/TMD2 and NBD1/NBD2 interfaces, respectively. ATP-dependent drug efflux involves changes between the open inward-facing (NBDs apart, extracellular loops (ECLs) close together) and the closed outward-facing (NBDs close together, ECLs apart) conformations. It is controversial, however, whether the open conformation only exists transiently in intact cells because of the presence of high levels of ATP. To test for the presence of an open conformation in intact cells, reporter cysteines were placed in extracellular loops 1 (A80C, N half) and 4 (R741C, C half). The rationale was that cysteines A80C/R741C would only come close enough to form a disulfide bond in an open conformation (6.9 Å apart) because they are separated widely (30.4 Å apart) in the closed conformation. It was observed that the mutant A80C/R741C cross-linked spontaneously (>90%) when expressed in cells. In contrast to previous reports showing that trapping P-gp in a closed conformation highly activated ATPase activity, here we show that A80C/R741C cross-linking inhibited ATPase activity and drug efflux. Both activities were restored when the cross-linked mutant was treated with a thiol-reducing agent. The results show that an open conformation can be readily detected in cells and that cross-linking of cysteines placed in ECLs 1 and 4 inhibits activity. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Advances and Challenges of Liposome Assisted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Lisa eSercombe

    2015-12-01

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

  6. Liposome-based drug delivery in breast cancer treatment

    International Nuclear Information System (INIS)

    Park, John W

    2002-01-01

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

  7. CTG-loaded liposomes as an approach for improving the intestinal absorption of asiaticoside in Centella Total Glucosides.

    Science.gov (United States)

    Wang, Jiayu; Ma, Changhua; Guo, Chengjie; Yuan, Ruijuan; Zhan, Xueyan

    2016-07-25

    Centella Total Glucosides (CTG),obtained from Centella asiatica (L.), have been shown to possess a multitude of pharmacological activities, however, oral administeration of CTG failed to fulfill their therapeutic potentials due to the low bioavailability. In this study, the author prepared the liposomes encapsulated CTG using the ethanol injection method in order to enhance their intestinal absorption. The average particle size and the polydispersityindex(PDI) of CTG-loaded liposome in a batch are 137.0nm and 0.283, and the CTG-loaded amounts in CTG-loaded liposomes were 0.177mgmL(-1) and the zeta potential of CTG-loaded lipsomes is -21.2mV. The TEM images of CTG-loaded lipsomes showed that CTG-loaded liposomes are round and maintain high structural integrity, and their DSC thermograms indicated that CTG might be incorporated into the aqueous phase of DPPC to become more stable. The everted rat gut sac model was used to study the absorption characteristic of CTG-loaded solution in rat intestines. The cumulative absorption amount (Q) and the cumulative absorption percentage (P%) of asiaticoside in the CTG-loaded liposome was significantly higher than that in CTG (Pabsorption of asiaticoside in the ileum of the rats by enhancing its transmembrane permeability. The above study will provide the experimental evidence and a reference for the development of the oral dosage forms of Centella total glucosides. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Influence of lipid concentration on encapsulation and particle size in the development of liposomal irinotecan

    Directory of Open Access Journals (Sweden)

    A. V. Stadnichenko

    2017-04-01

    Full Text Available Purpose. For creation of liposomal irinotecan form, the influence of lipid concentration on the encapsulation of the active substance and nanoparticle size was necessary to investigate. Materials and methods. We used «chemical gradient" method for liposomes formulation, in the variety of “pH gradient”. Ammonium citrate at pH 2.5 was used as internal buffer. Lipid film was obtained, by evaporation technics with further high pressure homogenization with Microfluidics Microfluidizer M-110P apparatus. “Chemical gradient” was created by ultrafiltration, with “Minim 2” apparatus. Ultrafiltration cartridge with an upper cut-off 30 kDa was used. Encapsulation was measured using HPLC methods developed in variant of gel chromatography, with Shimadzu LC-20 instrument. The particle size was measured by laser diffraction method withe “Zetasizer Nano ZS” instrument. Results. For the preparation of liposomes was applied a constant lipid ratio with varying of total lipid concentration. The ratio of lipids in the experiment was a phosphatidylcholine / cholesterol 80/20 % by weight. A total concentration was investigated in range from 10 mg/ml to 30 mg/ml. The number of extrusion cycles consisted from 3 cycles at 1500 bar, in case of 10 mg/ml concentration, to 17 cycles at 1500 bar, in case of 30 mg/ml concentration. Conclusions. It was shown that the lipid concentration from 25 mg/ml led to particles formation with size more than 5000 nm, and it was not possible to reduce them by high pressure homogenization method. It was proven that the most optimal, in terms of technology and the final characteristics of liposomes, was lipids in concentration 20 mg/ml. The degree of encapsulation in this case was 82 ± 0.98 %. The size of the liposomes was 106 nm, 5000 nm particles were absent.

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

    OpenAIRE

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

    1988-01-01

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

  10. Liposomes: structure, properties and methods of curative administration in organism

    Directory of Open Access Journals (Sweden)

    M. A. Kisyakova

    2010-07-01

    Full Text Available A review of data from scientific sources, devoted to problems of liposomes’ structure, properties and processes of formation was made. Advantages of liposomes used for medical purposes are shown. Methods of liposomes administration in an organism are characterised. Data on mechanisms of interaction between liposomes and cells, peculiarities of liposomes’ lipids composition and dependence of its tropism to definite organs and tissues are generalised.

  11. Vesicular lipidic systems, liposomes, PLO, and liposomes-PLO: characterization by electronic transmission microscopy.

    Science.gov (United States)

    Ruiz, M Adolfina; Clares, Beatriz; Morales, M Encarnacion; Gallardo, Visitacion

    2008-12-01

    Situations exist in which rapid administration of treatment, as well as maintenance of efficient concentrations for the longest possible time, turns out to be essential. In view of the previous treatment, the elaboration of liposomes, PLO (pluronic lecithin organogel), and the mixture of both is described, as well as their characterizations by electronic transmission microscopy, with the aim of finding out precisely the type of structure for both controlled release systems, its composition, size, homogeneity, and integrity. The period of study has been 90 days. Multilaminar and unilaminar vesicles smaller than 1 microm in diameter were seen in the liposomes, PLO, and liposomes-PLO formulations on transmission electron microscopic (TEM) observation. The technique of characterization reveals the progressive aggregation of the liposomas along the period of study. However, all the vesicles of PLO maintain a defined structure and only a light aggregation 60 days after the elaboration. Changes of morphology and aggregation of liposomas decreased after the incorporation of cholesterol (CH) to the liposomal matrix. The best results were obtained with the formulas liposomes-PLO, which maintain their individuality and integrity during the whole period of study. The combined formulation of liposomas and PLO showed an increase of stability of both lipid systems.

  12. Polyethylene glycol (PEG)-dendron phospholipids as innovative constructs for the preparation of super stealth liposomes for anticancer therapy.

    Science.gov (United States)

    Pasut, Gianfranco; Paolino, Donatella; Celia, Christian; Mero, Anna; Joseph, Adrian Steve; Wolfram, Joy; Cosco, Donato; Schiavon, Oddone; Shen, Haifa; Fresta, Massimo

    2015-02-10

    Pegylation of nanoparticles has been widely implemented in the field of drug delivery to prevent macrophage clearance and increase drug accumulation at a target site. However, the shielding effect of polyethylene glycol (PEG) is usually incomplete and transient, due to loss of nanoparticle integrity upon systemic injection. Here, we have synthesized unique PEG-dendron-phospholipid constructs that form super stealth liposomes (SSLs). A β-glutamic acid dendron anchor was used to attach a PEG chain to several distearoyl phosphoethanolamine lipids, thereby differing from conventional stealth liposomes where a PEG chain is attached to a single phospholipid. This composition was shown to increase liposomal stability, prolong the circulation half-life, improve the biodistribution profile and enhance the anticancer potency of a drug payload (doxorubicin hydrochloride). Copyright © 2014. Published by Elsevier B.V.

  13. Liposomally encapsulated diclofenac for sonophoresis induced systemic delivery.

    Science.gov (United States)

    Vyas, S P; Singh, R; Asati, R K

    1995-01-01

    Liposomes containing diclofenac, an anti-inflammatory agent were incorporated into an ointment base for topical application. The drug loaded liposomes were characterized for various physico-chemical attributes and drug efflux profile in in vitro. The systemic availability of drug from liposomes following topical application was evaluated in rats. The effect of sonophoresis on the drug release profile in vitro and systemic availability in vivo was established. The application of liposomal diclofenac resulted in localization of the drug at the site of application with slow systemic availability; however, with the application of ultrasound pulsed drug systemic levels could be achieved.

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

    Science.gov (United States)

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

    2017-11-01

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

  15. Liposomal Bupivacaine Injection Technique in Total Knee Arthroplasty.

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Najeeb Ullah

    2017-08-01

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

  17. 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

  18. Spontaneous uterine rupture

    African Journals Online (AJOL)

    ABSTRACT. Rupture of a gravid uterus is a surgical emergency. Predisposing factors include a scarred uterus. Spontaneous rupture of an unscarred uterus during pregnancy is a rare occurrence. We hereby present the case of a spontaneous complete uterine rupture at a gestational age of 34 weeks in a 35 year old patient ...

  19. Spontaneous intracranial hypotension.

    LENUS (Irish Health Repository)

    Fullam, L

    2012-01-31

    INTRODUCTION: Spontaneous\\/primary intracranial hypotension is characterised by orthostatic headache and is associated with characteristic magnetic resonance imaging findings. CASE REPORT: We present a case report of a patient with typical symptoms and classical radiological images. DISCUSSION: Spontaneous intracranial hypotension is an under-recognised cause of headache and can be diagnosed by history of typical orthostatic headache and findings on MRI brain.

  20. Inhibition of hexokinase-2 with targeted liposomal 3-bromopyruvate in an ovarian tumor spheroid model of aerobic glycolysis

    Directory of Open Access Journals (Sweden)

    Gandham SK

    2015-07-01

    Full Text Available Srujan Kumar Gandham, Meghna Talekar, Amit Singh, Mansoor M Amiji Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA, USA Background: The objective of this study was to evaluate the expression levels of glycolytic markers, especially hexokinase-2 (HK2, using a three-dimensional multicellular spheroid model of human ovarian adenocarcinoma (SKOV-3 cells and to develop an epidermal growth factor receptor-targeted liposomal formulation for improving inhibition of HK2 and the cytotoxicity of 3-bromopyruvate (3-BPA. Methods: Multicellular SKOV-3 tumor spheroids were developed using the hanging drop method and expression levels of glycolytic markers were examined. Non-targeted and epidermal growth factor receptor-targeted liposomal formulations of 3-BPA were formulated and characterized. Permeability and cellular uptake of the liposomal formulations in three-dimensional SKOV-3 spheroids was evaluated using confocal microscopy. The cytotoxicity and HK2 inhibition potential of solution form of 3-BPA was compared to the corresponding liposomal formulation by using cell proliferation and HK2 enzymatic assays. Results: SKOV-3 spheroids were reproducibly developed using the 96-well hanging drop method, with an average size of 900 µm by day 5. HK2 enzyme activity levels under hypoxic conditions were found to be higher than under normoxic conditions (P<0.0001, Student’s t-test, unpaired and two-tailed. Liposomal formulations (both non-targeted and targeted of 3-BPA showed a more potent inhibitory effect (P<0.001, Student’s t-test, unpaired and two-tailed at a dose of 50 µM than the aqueous solution form at 3, 6, and 24 hours post administration. Similarly, the cytotoxic activity 3-BPA at various concentrations (10 µM–100 µM showed that the liposomal formulations had an enhanced cytotoxic effect of 2–5-fold (P<0.0001, Student’s t-test, unpaired and two-tailed when compared to the aqueous solution form

  1. Interaction of liposomal formulations of meta-tetra(hydroxyphenyl)chlorin (temoporfin) with serum proteins: protein binding and liposome destruction.

    Science.gov (United States)

    Reshetov, Vadzim; Zorin, Vladimir; Siupa, Agnieszka; D'Hallewin, Marie-Ange; Guillemin, François; Bezdetnaya, Lina

    2012-01-01

    mTHPC is a non polar photosensitizer used in photodynamic therapy. To improve its solubility and pharmacokinetic properties, liposomes were proposed as drug carriers. Binding of liposomal mTHPC to serum proteins and stability of drug carriers in serum are of major importance for PDT efficacy; however, neither was reported before. We studied drug binding to human serum proteins using size-exclusion chromatography. Liposomes destruction in human serum was measured by nanoparticle tracking analysis (NTA). Inclusion of mTHPC into conventional (Foslip(®)) and PEGylated (Fospeg(®)) liposomes does not affect equilibrium serum protein binding compared with solvent-based mTHPC. At short incubation times the redistribution of mTHPC from Foslip(®) and Fospeg(®) proceeds by both drug release and liposomes destruction. At longer incubation times, the drug redistributes only by release. The release of mTHPC from PEGylated vesicles is delayed compared with conventional liposomes, alongside with greatly decreased liposomes destruction. Thus, for long-circulation times the pharmacokinetic behavior of Fospeg(®) could be influenced by a combination of protein- and liposome-bound drug. The study highlights the modes of interaction of photosensitizer-loaded nanovesicles in serum to predict optimal drug delivery and behavior in vivo in preclinical models, as well as the novel application of NTA to assess the destruction of liposomes. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

  2. Interaction of cationic drugs with liposomes.

    Science.gov (United States)

    Howell, Brett A; Chauhan, Anuj

    2009-10-20

    Interactions between cationic drugs and anionic liposomes were studied by measuring binding of drugs and the effect of binding on liposome permeability. The measurements were analyzed in the context of a continuum model based on electrostatic interactions and a Langmuir isotherm. Experiments and modeling indicate that, although electrostatic interactions are important, the fraction of drug sequestered in the double-layer is negligible. The majority of drug enters the bilayer with the charged regions interacting with the charged lipid head groups and the lipophilic regions associated with the bilayer. The partitioning of the drug can be described by a Langmuir isotherm with the electrostatic interactions increasing the sublayer concentration of the drug. The binding isotherms are similar for all tricyclic antidepressants (TCA). Bupivacaine (BUP) binds significantly less compared to TCA because its structure is such that the charged region has minimal interactions with the lipid heads once the BUP molecule partitions inside the bilayer. Conversely, the TCAs are linear with distinct hydrophilic and lipophilic regions, allowing the lipophilic regions to lie inside the bilayer and the hydrophilic regions to protrude out. This conformation maximizes the permeability of the bilayer, leading to an increased release of a hydrophilic fluorescent dye from liposomes.

  3. The (perceived) meaning of spontaneous thoughts.

    Science.gov (United States)

    Morewedge, Carey K; Giblin, Colleen E; Norton, Michael I

    2014-08-01

    Spontaneous thoughts, the output of a broad category of uncontrolled and inaccessible higher order mental processes, arise frequently in everyday life. The seeming randomness by which spontaneous thoughts arise might give people good reason to dismiss them as meaningless. We suggest that it is precisely the lack of control over and access to the processes by which they arise that leads people to perceive spontaneous thoughts as revealing meaningful self-insight. Consequently, spontaneous thoughts potently influence judgment. A series of experiments provides evidence supporting two hypotheses. First, we hypothesize that the more a thought is perceived to be spontaneous, the more it is perceived to provide meaningful self-insight. Participants perceived more spontaneous kinds of thought (e.g., intuition) to reveal greater self-insight than did more controlled kinds of thought in Study 1 (e.g., deliberation). In Studies 2 and 3, participants perceived thoughts with the same content and target to reveal greater self-insight when spontaneously rather than deliberately generated (i.e., childhood memories and impressions formed). Second, we hypothesize that the greater self-insight attributed to thoughts that are (perceived to be) spontaneous leads those thoughts to more potently influence judgment. Participants felt more sexually attracted to an attractive person whom they thought of spontaneously than deliberately in Study 4, and reported their commitment to a current romantic relationship would be more affected by the spontaneous rather than deliberate recollection of a good or bad experience with their romantic partner in Study 5. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  4. 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.

    1980-01-01

    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

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

    Science.gov (United States)

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

    2006-11-01

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

  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. 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

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

    International Nuclear Information System (INIS)

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

    1983-01-01

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

  9. Hydrogel Containing Nanoparticle-Stabilized Liposomes for Topical Antimicrobial Delivery

    Science.gov (United States)

    2015-01-01

    Adsorbing small charged nanoparticles onto the outer surfaces of liposomes has become an effective strategy to stabilize liposomes against fusion prior to “seeing” target bacteria, yet allow them to fuse with the bacteria upon arrival at the infection sites. As a result, nanoparticle-stabilized liposomes have become an emerging drug delivery platform for treatment of various bacterial infections. To facilitate the translation of this platform for clinical tests and uses, herein we integrate nanoparticle-stabilized liposomes with hydrogel technology for more effective and sustained topical drug delivery. The hydrogel formulation not only preserves the structural integrity of the nanoparticle-stabilized liposomes, but also allows for controllable viscoeleasticity and tunable liposome release rate. Using Staphylococcus aureus bacteria as a model pathogen, we demonstrate that the hydrogel formulation can effectively release nanoparticle-stabilized liposomes to the bacterial culture, which subsequently fuse with bacterial membrane in a pH-dependent manner. When topically applied onto mouse skin, the hydrogel formulation does not generate any observable skin toxicity within a 7-day treatment. Collectively, the hydrogel containing nanoparticle-stabilized liposomes hold great promise for topical applications against various microbial infections. PMID:24483239

  10. General and programmable synthesis of hybrid liposome/metal nanoparticles.

    Science.gov (United States)

    Lee, Jin-Ho; Shin, Yonghee; Lee, Wooju; Whang, Keumrai; Kim, Dongchoul; Lee, Luke P; Choi, Jeong-Woo; Kang, Taewook

    2016-12-01

    Hybrid liposome/metal nanoparticles are promising candidate materials for biomedical applications. However, the poor selectivity and low yield of the desired hybrid during synthesis pose a challenge. We designed a programmable liposome by selective encoding of a reducing agent, which allows self-crystallization of metal nanoparticles within the liposome to produce stable liposome/metal nanoparticles alone. We synthesized seven types of liposome/monometallic and more complex liposome/bimetallic hybrids. The resulting nanoparticles are tunable in size and metal composition, and their surface plasmon resonance bands are controllable in visible and near infrared. Owing to outer lipid bilayer, our liposome/Au nanoparticle shows better colloidal stability in biologically relevant solutions as well as higher endocytosis efficiency than gold nanoparticles without the liposome. We used this hybrid in intracellular imaging of living cells via surface-enhanced Raman spectroscopy, taking advantage of its improved physicochemical properties. We believe that our method greatly increases the utility of metal nanoparticles in in vivo applications.

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

    African Journals Online (AJOL)

    2017-09-03

    Sep 3, 2017 ... the effects of liposomal carriers, phytic acid, zinc and particle size on iron transport using Caco-2 cell models. Methods: Caco-2 cells were .... port of ferrous glycinate liposomes could result from the protection of ferrous glycinate by ..... 1998;37:12875-12883. 23. Albanese A, Tang PS, Chan WC The effect of.

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

    Science.gov (United States)

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

    2012-02-07

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

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

    African Journals Online (AJOL)

    DS liposomes with good bioavailability. Keywords: Liposome, Drug delivery, Palm oil, Diclofenac. Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus,. International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index Copernicus, EBSCO, African. Index Medicus ...

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

    Science.gov (United States)

    Yue, Xiuli; Dai, Zhifei

    2014-05-01

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

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

    International Nuclear Information System (INIS)

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

    2003-01-01

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

  16. The clearance of liposomes administered by the intramuscular route

    International Nuclear Information System (INIS)

    Arrowsmith, M.; Mills, S.N.

    1982-01-01

    Iodine 131-labelled lecithin was used to label liposomes entrapping cortisone-21-palmitate. The lecithin was injected into the fascia latae muscles of rabbits and the percentage of the initial dose remaining at certain time intervals was calculated from gamma camera image data. Release from the intramuscular site occurs by diffusion from intact liposomes. (U.K.)

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

    Science.gov (United States)

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

    2017-12-01

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

  18. Arabidopsis dynamin-related protein 1A polymers bind, but do not tubulate, liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Backues, Steven K. [Department of Biochemistry, University of Wisconsin - Madison, 433 Babcock Dr., Madison, WI 53706 (United States); Bednarek, Sebastian Y., E-mail: sybednar@wisc.edu [Department of Biochemistry, University of Wisconsin - Madison, 433 Babcock Dr., Madison, WI 53706 (United States)

    2010-03-19

    The Arabidopsis dynamin-related protein 1A (AtDRP1A) is involved in endocytosis and cell plate maturation in Arabidopsis. Unlike dynamin, AtDRP1A does not have any recognized membrane binding or protein-protein interaction domains. We report that GTPase active AtDRP1A purified from Escherichia coli as a fusion to maltose binding protein forms homopolymers visible by negative staining electron microscopy. These polymers interact with protein-free liposomes whose lipid composition mimics that of the inner leaflet of the Arabidopsis plasma membrane, suggesting that lipid-binding may play a role in AtDRP1A function. However, AtDRP1A polymers do not appear to assemble and disassemble in a dynamic fashion and do not have the ability to tubulate liposomes in vitro, suggesting that additional factors or modifications are necessary for AtDRP1A's in vivo function.

  19. A pulse radiolysis study of the dynamics of ascorbic acid free radicals within a liposomal environment.

    Science.gov (United States)

    Kobayashi, Kazuo; Seike, Yumiko; Saeki, Akinori; Kozawa, Takahiro; Takeuchi, Fusako; Tsubaki, Motonari

    2014-10-06

    The dynamics of free-radical species in a model cellular system are examined by measuring the formation and decay of ascorbate radicals within a liposome with pulse radiolysis techniques. Upon pulse radiolysis of an N2O-saturated aqueous solution containing ascorbate-loaded liposome vesicles, ascorbate radicals are formed by the reaction of OH(·) radicals with ascorbate in unilamellar vesicles exclusively, irrespective of the presence of vesicle lipids. The radicals are found to decay rapidly compared with the decay kinetics in an aqueous solution. The distinct radical reaction kinetics in the vesicles and in bulk solution are characterized, and the kinetic data are analyzed. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Arabidopsis dynamin-related protein 1A polymers bind, but do not tubulate, liposomes

    International Nuclear Information System (INIS)

    Backues, Steven K.; Bednarek, Sebastian Y.

    2010-01-01

    The Arabidopsis dynamin-related protein 1A (AtDRP1A) is involved in endocytosis and cell plate maturation in Arabidopsis. Unlike dynamin, AtDRP1A does not have any recognized membrane binding or protein-protein interaction domains. We report that GTPase active AtDRP1A purified from Escherichia coli as a fusion to maltose binding protein forms homopolymers visible by negative staining electron microscopy. These polymers interact with protein-free liposomes whose lipid composition mimics that of the inner leaflet of the Arabidopsis plasma membrane, suggesting that lipid-binding may play a role in AtDRP1A function. However, AtDRP1A polymers do not appear to assemble and disassemble in a dynamic fashion and do not have the ability to tubulate liposomes in vitro, suggesting that additional factors or modifications are necessary for AtDRP1A's in vivo function.

  1. Liposomal encapsulation masks genotoxicity of a chemotherapeutic agent in regulatory toxicology assessments.

    Science.gov (United States)

    Alexander, Jenolyn F; Aguirre-Villarreal, David; Godin, Biana

    2017-04-01

    The burgeoning application of nanotechnology to a variety of industries including cosmetics, food, medicine and materials has led to the exploration of nanotoxicology as a trending subject of research. However the role of a nanovector, in affecting the mutagenicity of its therapeutic payload has not yet been investigated. In this study, we compare the mutagenicity of the free drug - doxorubicin hydrochloride with its nanoencapsulated form - doxorubicin loaded liposome, using conventional methods required for regulatory approval. Contrary to free doxorubicin, doxorubicin encapsulated liposome expressed a significantly lower mutant frequency in the Ames assay, and was non-genotoxic in the in vitro micronucleus assay. Further investigation of the systems' cytotoxicity and their interaction with the bacterial cell envelope, suggests that the modification of the test parameters and release of the encapsulated drug prior to the Ames test show comparable mutagenic potential of the nanotherapeutic system to a free drug. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Corneal Epithelial Wound Healing Promoted by Verbascoside-Based Liposomal Eyedrops

    Directory of Open Access Journals (Sweden)

    Luigi Ambrosone

    2014-01-01

    Full Text Available Different liposomal formulations were prepared to identify those capable of forming eyedrops for corneal diseases. Liposomes with neutral or slightly positive surface charge interact very well with the cornea. Then these formulations were loaded with verbascoside to heal a burn of corneal epithelium induced by alkali. The cornea surface affected involved in wound was monitored as a function of time. Experimental results were modeled by balance equation between the rate of healing, due to the flow of phenylpropanoid, and growth of the wound. The results indicate a latency time of only three hours and furthermore the corneal epithelium heals in 48 hours. Thus, the topical administration of verbascoside appears to reduce the action time of cells, as verified by histochemical and immunofluorescence assays.

  3. Corneal Epithelial Wound Healing Promoted by Verbascoside-Based Liposomal Eyedrops

    Science.gov (United States)

    Ambrosone, Luigi; Guerra, Germano; Cinelli, Mariapia; Filippelli, Mariaelena; Mosca, Monica; Vizzarri, Francesco; Giorgio, Dario; Costagliola, Ciro

    2014-01-01

    Different liposomal formulations were prepared to identify those capable of forming eyedrops for corneal diseases. Liposomes with neutral or slightly positive surface charge interact very well with the cornea. Then these formulations were loaded with verbascoside to heal a burn of corneal epithelium induced by alkali. The cornea surface affected involved in wound was monitored as a function of time. Experimental results were modeled by balance equation between the rate of healing, due to the flow of phenylpropanoid, and growth of the wound. The results indicate a latency time of only three hours and furthermore the corneal epithelium heals in 48 hours. Thus, the topical administration of verbascoside appears to reduce the action time of cells, as verified by histochemical and immunofluorescence assays. PMID:25165705

  4. Characteristics of quercetin interactions with liposomal and vacuolar membranes.

    Science.gov (United States)

    Pawlikowska-Pawlęga, Bożena; Dziubińska, Halina; Król, Elżbieta; Trębacz, Kazimierz; Jarosz-Wilkołazka, Anna; Paduch, Roman; Gawron, Antoni; Gruszecki, Wieslaw I

    2014-01-01

    Quercetin (3,3',4',5,7-pentahydroxyflavone) is claimed to exert many beneficial health effects. With application of (1)H NMR (nuclear magnetic resonance) and FTIR (Fourier-transform infrared) techniques, quercetin interaction with liposomes formed with dipalmitoylphosphatidylcholine (DPPC) was analyzed. Patch-clamp technique was employed to study quercetin effects at single channel level of vacuolar membranes in the liverwort Conocephalum conicum. Light and electron microscopy were applied to study quercetin effects on human negroid cervix carcinoma cells (HeLa). Enzymatic measurements along with DPPH (1,1-diphenyl-2-picrylhydrazyl) bioassay were performed to investigate the influence of quercetin on antioxidant enzymes and reactive oxygen species (ROS) production. The inclusion of quercetin to the membrane exerted pronounced ordering effect on the motional freedom of lipids in the head group region as manifested by broadening of the (1)H NMR spectral line representing the choline groups. FTIR analysis revealed quercetin incorporation into DPPC liposomes via hydrogen bonding between its own hydroxyl groups and lipid polar head groups in the C-O-P-O-C segment. Both, FTIR and NMR techniques indicated also quercetin spectral effects in the region corresponding to alkyl chains. Patch-clamp experiments showed that quercetin stabilizes tonoplast and promotes a close state of SV channels. Microscopic observations of HeLa cells revealed characteristic changes in ultrastructure and morphology of the examined cells in comparison to control cells. Pretreatment of HeLa cells with quercetin alleviated H2O2-induced cell injury by improving redox balance as indicated by the increase in glutathione content and SOD (superoxide dismutase) levels as well as by the decrease in ROS level. \\In conclusion, the incorporation, distribution and the changes of biophysical properties of the membranes are very important for the effectiveness of phenolic compounds as antioxidant and anticancer

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

    Science.gov (United States)

    Michel*, Raphael; Gradzielski*, Michael

    2012-01-01

    In the past few years, growing attention has been devoted to the study of the interactions taking place in mixed systems of phospholipid membranes (for instance in the form of vesicles) and hard nanoparticles (NPs). In this context liposomes (vesicles) may serve as versatile carriers or as a model system for biological membranes. Research on these systems has led to the observation of novel hybrid structures whose morphology strongly depends on the charge, composition and size of the interacting colloidal species as well as on the nature (pH, ionic strength) of their dispersing medium. A central role is played by the phase behaviour of phospholipid bilayers which have a tremendous influence on the liposome properties. Another central aspect is the incorporation of nanoparticles into vesicles, which is intimately linked to the conditions required for transporting a nanoparticle through a membrane. Herein, we review recent progress made on the investigations of the interactions in liposome/nanoparticle systems focusing on the particularly interesting structures that are formed in these hybrid systems as well as their potential applications. PMID:23109874

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

    Science.gov (United States)

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

    2017-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Michael Gradzielski

    2012-09-01

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

  8. Spontaneous Pneumomediastinum: Hamman Syndrome

    Directory of Open Access Journals (Sweden)

    Tushank Chadha, BS

    2018-04-01

    significant fat stranding. The image also showed an intraluminal stent traversing the gastric antrum and gastric pylorus with no indication of obstruction. Circumferential mural thickening of the gastric antrum and body were consistent with the patient’s history of gastric adenocarcinoma. The shotty perigastric lymph nodes with associated fat stranding, along the greater curvature of the distal gastric body suggested local regional nodal metastases and possible peritoneal carcinomatosis. The thoracic CT scans showed extensive pneumomediastinum that tracked into the soft tissues of the neck, which given the history of vomiting also raised concern for esophageal perforation. There was still no evidence of mediastinal abscess or fat stranding. Additionally, a left subclavian vein port catheter, which terminates with tip at the cavoatrial junction of the superior vena cava can also be seen on the image. Discussion: Spontaneous Pneumomediastinum, also known as Hamman syndrome, is defined by the uncommon incidence of free air in the mediastinum due to the bursting of alveoli, as a result of extended spells of shouting, coughing, or vomiting.1,2 The condition is diagnosed when a clear cause (aerodigestive rupture, barotrauma, infection secondary to gas-forming organisms3 for pneumomediastinum cannot be clearly identified on diagnostic studies. Macklin and Macklin were the first to note the pathogenesis of the syndrome and explained that the common denominator to spontaneous pneumomediastinum was that increased alveolar pressure leads to alveolar rupture.3 Common clinical findings for spontaneous pneumomediastinum include: chest pain, dyspnea, cough, and emesis.4 The condition is not always readily recognized on initial presentation in part for its rare incidence, estimated to be approximately 1 in every 44,500 ED patients3and also because of the non-specific presenting symptoms. For this patient, there was no clear singular cause, and therefore she received care for spontaneous

  9. Designing of 'intelligent' liposomes for efficient delivery of drugs.

    Science.gov (United States)

    Voinea, Manuela; Simionescu, Maya

    2002-01-01

    The liposome- vesicles made by a double phospholipid layers which may encapsulate aqueous solutions- have been introduced as drug delivery vehicles due to their structural flexibility in size, composition and bilayer fluidity as well as their ability to incorporate a large variety of both hydrophilic and hydrophobic compounds. With time the liposome formulations have been perfected so as to serve certain purposes and this lead to the design of "intelligent" liposomes which can stand specifically induced modifications of the bilayers or can be surfaced with different ligands that guide them to the specific target sites. We present here a brief overview of the current strategies in the design of liposomes as drug delivery carriers and the medical applications of liposomes in humans.

  10. Mechanical properties of a giant liposome studied using optical tweezers

    Science.gov (United States)

    Shitamichi, Yoko; Ichikawa, Masatoshi; Kimura, Yasuyuki

    2009-09-01

    The mechanical properties of a micrometer-sized giant liposome are studied by deforming it from the inside using dual-beam optical tweezers. As the liposome is extended, its shape changes from a sphere to a lemon shape, and finally, a tubular part is generated. The surface tension σ and the bending rigidity κ of the lipid membrane are obtained from the measured force-extension curve. In a one-phase liposome, it was found that σ increases as the charged component increases but κ remains approximately constant. In a two-phase liposome, the characteristic deformation and the force-extension curve differ from those observed for the one-phase liposome.

  11. Liposomal Formulations in Clinical Use: An Updated Review

    Directory of Open Access Journals (Sweden)

    Upendra Bulbake

    2017-03-01

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

  12. Electromagnetic field triggered drug and chemical delivery via liposomes

    Science.gov (United States)

    Liburdy, Robert P.

    1993-01-01

    The present invention relates to a system and to a method of delivering a drug to a preselected target body site of a patient, comprising the steps of encapsulating the chemical agent within liposomes, essentially temperature insensitive, i.e. not having a specific predetermined phase transition temperature within the specific temperature range of drug administration; administering the liposomes to the target body site; and subjecting the target body site to nonionizing electromagnetic fields in an area of the preselected target body in order to release said chemical agent from the liposomes at a temperature of between about +10 and 65.degree. C. The invention further relates to the use of said liposomes to bind to the surface of or to enter target tissue or an organ in a living system, and, when subjected to a nonionizing field, to release a drug from the liposomes into the target site.

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

    Science.gov (United States)

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

    2017-06-01

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

  14. Spontaneous Trait Inferences on Social Media.

    Science.gov (United States)

    Levordashka, Ana; Utz, Sonja

    2017-01-01

    The present research investigates whether spontaneous trait inferences occur under conditions characteristic of social media and networking sites: nonextreme, ostensibly self-generated content, simultaneous presentation of multiple cues, and self-paced browsing. We used an established measure of trait inferences (false recognition paradigm) and a direct assessment of impressions. Without being asked to do so, participants spontaneously formed impressions of people whose status updates they saw. Our results suggest that trait inferences occurred from nonextreme self-generated content, which is commonly found in social media updates (Experiment 1) and when nine status updates from different people were presented in parallel (Experiment 2). Although inferences did occur during free browsing, the results suggest that participants did not necessarily associate the traits with the corresponding status update authors (Experiment 3). Overall, the findings suggest that spontaneous trait inferences occur on social media. We discuss implications for online communication and research on spontaneous trait inferences.

  15. Evaluation of antinociceptive activity of nanoliposome-encapsulated and free-form diclofenac in rats and mice.

    Science.gov (United States)

    Goh, Jun Zheng; Tang, Sook Nai; Chiong, Hoe Siong; Yong, Yoke Keong; Zuraini, Ahmad; Hakim, Muhammad Nazrul

    2015-01-01

    Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, antinociceptive, and antipyretic activities. Liposomes have been shown to improve the therapeutic efficacy of encapsulated drugs. The present study was conducted to compare the antinociceptive properties between liposome-encapsulated and free-form diclofenac in vivo via different nociceptive assay models. Liposome-encapsulated diclofenac was prepared using the commercialized proliposome method. Antinociceptive effects of liposome-encapsulated and free-form diclofenac were evaluated using formalin test, acetic acid-induced abdominal writhing test, Randall-Selitto paw pressure test, and plantar test. The results of the writhing test showed a significant reduction of abdominal constriction in all treatment groups in a dose-dependent manner. The 20 mg/kg liposome-encapsulated diclofenac demonstrated the highest antinociceptive effect at 78.97% compared with 55.89% in the free-form group at equivalent dosage. Both liposome-encapsulated and free-form diclofenac produced significant results in the late phase of formalin assay at a dose of 20 mg/kg, with antinociception percentages of 78.84% and 60.71%, respectively. Significant results of antinociception were also observed in both hyperalgesia assays. For Randall-Sellito assay, the highest antinociception effect of 71.38% was achieved with 20 mg/kg liposome-encapsulated diclofenac, while the lowest antinociceptive effect of 17.32% was recorded with 0 mg/kg liposome formulation, whereas in the plantar test, the highest antinociceptive effect was achieved at 56.7% with 20 mg/kg liposome-encapsulated diclofenac, and the lowest effect was shown with 0 mg/kg liposome formulation of 8.89%. The present study suggests that liposome-encapsulated diclofenac exhibits higher antinociceptive efficacy in a dose-dependent manner in comparison with free-form diclofenac.

  16. Analysis of individual lipoproteins and liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Robbins, D.L.; Keller, R.A.; Nolan, J.P. [and others

    1997-08-01

    We describe the application of single molecule detection (SMD) technologies for the analysis of natural (serum lipoproteins) and synthetic (liposomes) transport systems. The need for advanced analytical procedures of these complex and important systems is presented with the specific enhancements afforded by SMD with flowing sample streams. In contrast to bulk measurements which yield only average values, measurement of individual species allows creation of population histograms from heterogeneous samples. The data are acquired in minutes and the analysis requires relatively small sample quantities. Preliminary data are presented from the analysis of low density lipoprotein, and multilamellar and unilamellar vesicles.

  17. The Role of Liposomal CpG ODN on the Course of L. major Infection in BALB/C Mice

    Directory of Open Access Journals (Sweden)

    H Hejazi

    2010-02-01

    Full Text Available "nBackground: Historically, leishmanization is the most effective protective measure against Cutaneous Leishmaniasis (CL, CL lesion induced by leishmanization sometimes takes a long time to heal. Ma­nipulation of leishmanization inoculums needed to induce a mild and acceptable CL lesion. The aim of this study was to explore if liposomal form of CpG ODN (Cytosin phosphate Guanin Oligodeoxynu­cleotides mixed with Leishmania major   would induce a milder lesion size in Balb/c mice."nMethods: This study was performed in Biotechnology Research Center, Mashhad, and Center for Re­search and Training in Skin Diseases and Leprosy, Tehran, Iran during 2008-2009.  mice were subcutaneously (SC inoculated with L. major mixed with liposomal form of CpG ODN, or L. major plus free CpG ODN, or L. major mixed with empty liposomes or L. major in PBS. The lesion onset and the size of lesion were recorded; the death rate was also monitored. "nResult: Footpad thickness was significantly (P<0.01 smaller, death rate was also significantly (P<0.05 lower in the mice received L. major mixed with liposomal CpG ODN or free CpG ODN than control groups received L. major in PBS or L. major plus liposomes, also mice which received L. ma­jor mixed with CpG ODN in soluble form showed a significantly (P < 0.001 smaller lesion size than control groups."nConclusion: CpG ODN seems to be an appropriate immunopotentiator mixed with Leishmania stabi­late in leishmanization.

  18. 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.

  19. Liposomal formulation for co-delivery of paclitaxel and lapatinib, preparation, characterization and optimization.

    Science.gov (United States)

    Ravar, Fatemeh; Saadat, Ebrahim; Kelishadi, Pouya Dehghan; Dorkoosh, Farid A

    2016-09-01

    Paclitaxel (PTX) is one of the most promising natural anticancer agents with a wide therapeutic range which is limited by its hydrophobic nature, low therapeutic index and more importantly, the emergence of multidrug resistance (MDR). Lapatinib (LPT) is a dual tyrosine kinase inhibitor with a significant potential to inhibit p-glycoproteins which form one of the main groups of proteins responsible for efflux pump mediated MDR. To overcome the PTX related MDR, a novel liposomal formulation was optimized for co-delivery of PTX and LPT by applying the D-optimal response surface methodology. The encapsulation efficiency (EE%) of the optimized formulation for LPT and PTX was 52 ± 3% and 68 ± 5, respectively. The optimized formulation showed a narrow size distribution with the average of 235 ± 12 nm. The transmission electron microscopy image showed that liposomes were round in shape and discrete. The release profile exhibited 93% and 71% drug release for PTX and LPT after 40 h in the sink condition. The differential scanning calorimetry analysis indicated the conversion of both drugs from crystalline state to molecular state in the optimized lyophilized formulation. The cytotoxicity of the prepared formulation was studied against 4T1 murine mammary cells. The liposomal formulation showed better cytotoxicity in comparison to the binary mixture of free drugs.

  20. Development of a Rapidly Dissolvable Oral Pediatric Formulation for Mefloquine Using Liposomes.

    Science.gov (United States)

    Tang, Wei-Lun; Tang, Wei-Hsin; Chen, Weihsu Claire; Diako, Charles; Ross, Carolyn F; Li, Shyh-Dar

    2017-06-05

    Mefloquine (Mef), a poorly soluble and highly bitter drug, has been used for malaria prophylaxis and treatment. The dosage form for Mef is mostly available as adult tablets, and thus children under the age of 5 suffer from poor medication adherence. We have developed a stable, rapidly dissolvable, and palatable pediatric formulation for Mef using liposomes composed of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol with a mean diameter of ∼110 nm. Mef was actively loaded into the liposomes via an ammonium sulfate gradient using the solvent-assisted loading technology (SALT) developed in our lab. Complete loading of Mef inside the liposomal core was achieved at a high drug-to-lipid ratio (D/L) of 0.1-0.2 (w/w), and the final drug content in the formulation was ∼8 mg/mL, well above the solubility of Mef (3 months. In mice, orally delivered liquid and lyophilized Mef-Lipo displayed comparable absorption with bioavailability (BA) of 81-86%, while the absorption of the standard Mef suspension was significantly lower with BA of 70% and 20% decreased maximal plasma concentration and area under the curve. Our data suggest that the Mef-Lipo was a stable, palatable, and bioavailable formulation that might be suitable for pediatric use.

  1. Immobilization of aloin encapsulated into liposomes in layer-by-layer films for transdermal drug delivery.

    Science.gov (United States)

    Xavier, Aline Carla Farrapo; de Moraes, Marli Leite; Ferreira, Marystela

    2013-04-01

    Layer-by-layer (LbL) films have been exploited in drug delivery systems that may be used in the form of patches, but the encapsulation of poor water soluble drugs and their release with a controlled rate are still major challenges to be faced. In this paper, we demonstrate the controlled release of aloin (barbaloin), an important component of the widely used Aloe vera, encapsulated into liposomes and immobilized in LbL films with a polyelectrolyte. With a systematic study using fluorescence spectroscopy of aloin release from solutions and from LbL films with different phospholipid liposomes, we inferred that optimized release was achieved with aloin incorporated into palmitoyl oleyl phosphatidyl glycerol (POPG) or dipalmitoyl phosphatidyl glycerol (DPPG) liposomes immobilized in LbL films. Significantly, with this optimized system aloin was almost completely released within 30 h, with a small release rate at the end, which followed a sharp release in the first 5h. Upon comparing the rates of the distinct systems, we conclude that the main factors controlling the release are the electrostatic interactions involving the negatively charged phospholipids. Because these interactions can be tuned in LbL films, the approach used here opens the way for new drug delivery systems to be developed with fine control of the drug release. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. siRNA-loaded liposomes: Inhibition of encystment of Acanthamoeba and toxicity on the eye surface.

    Science.gov (United States)

    Faber, Kathrin; Zorzi, Giovanni K; Brazil, Nathalya T; Rott, Marilise B; Teixeira, Helder F

    2017-09-01

    Current treatments for Acanthamoeba keratitis are unspecific. Because of the presence of the resilient cyst form of the parasite, the infection is persistent. Silencing the key protein of cyst formation, glycogen phosphorylase, has shown potential for reducing encystment processes of the Acanthamoeba trophozoite. However, a suitable carrier to protect and deliver siRNA sequences is still needed. DOPE:DSPE-PEG liposomes were prepared by three different techniques and used to associate a therapeutic siRNA sequence. Liposomes prepared by film hydration followed by membrane extrusion were considered the most adequate ones with average size of 250 nm and zeta potential of +45 mV, being able to associate siRNA for at least 24 hr in culture medium. siRNA-liposomes could inhibit up to 66% of the encystment process. Cell viability studies demonstrated MTT reduction capacity higher than 80% after 3 hr incubation with this formulation. After 24 hr of incubation, LDH activity ranged for both the formulations from around 4% to 40%. In vivo tolerance studies in mice showed no macroscopic alteration in the eye structures up to 24 hr after eight administrations during 1 day. Histological studies showed regular tissue architecture without any morphological alteration. Overall, these results suggest that the formulations developed are a promising new strategy for the treatment of ocular keratitis caused by Acanthamoeba spp. © 2017 John Wiley & Sons A/S.

  3. Heparin octasaccharide decoy liposomes inhibit replication of multiple viruses

    Science.gov (United States)

    Hendricks, Gabriel L.; Velazquez, Lourdes; Pham, Serena; Qaisar, Natasha; Delaney, James C.; Viswanathan, Karthik; Albers, Leila; Comolli, James C.; Shriver, Zachary; Knipe, David M.; Kurt-Jones, Evelyn A.; Fygenson, Deborah K.; Trevejo, Jose M.

    2016-01-01

    Heparan sulfate (HS) is a ubiquitous glycosaminoglycan that serves as a cellular attachment site for a number of significant human pathogens, including respiratory syncytial virus (RSV), human parainfluenza virus 3 (hPIV3), and herpes simplex virus (HSV). Decoy receptors can target pathogens by binding to the receptor pocket on viral attachment proteins, acting as ‘molecular sinks’ and preventing the pathogen from binding to susceptible host cells. Decoy receptors functionalized with HS could bind to pathogens and prevent infection, so we generated decoy liposomes displaying HS-octasaccharide (HS-octa). These decoy liposomes significantly inhibited RSV, hPIV3, and HSV infectivity in vitro to a greater degree than the original HS-octa building block. The degree of inhibition correlated with the density of HS-octa displayed on the liposome surface. Decoy liposomes with HS-octa inhibited infection of viruses to a greater extent than either full-length heparin or HS-octa alone. Decoy liposomes were effective when added prior to infection or following the initial infection of cells in vitro. By targeting the well-conserved receptor-binding sites of HS-binding viruses, decoy liposomes functionalized with HS-octa are a promising therapeutic antiviral agent and illustrate the utility of the liposome delivery platform. PMID:25637710

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

    Science.gov (United States)

    Lankalapalli, Srinivas; Tenneti, V S Vinai Kumar

    2016-01-01

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

  5. Liposomes, a promising strategy for clinical application of platinum derivatives.

    Science.gov (United States)

    Zalba, Sara; Garrido, María J

    2013-06-01

    Liposomes represent a versatile system for drug delivery in various pathologies. Platinum derivatives have been demonstrated to have therapeutic efficacy against several solid tumors. But their use is limited due to their side effects. Since liposomal formulations are known to reduce the toxicity of some conventional chemotherapeutic drugs, the encapsulation of platinum derivatives in these systems may be useful in reducing toxicity and maintaining an adequate therapeutic response. This review describes the strategies applied to platinum derivatives in order to improve their therapeutic activity, while reducing the incidence of side effects. It also reviews the results found in the literature for the different platinum-drugs liposomal formulations and their current status. The design of liposomes to achieve effectiveness in antitumor treatment is a goal for platinum derivatives. Liposomes can change the pharmacokinetic parameters of these encapsulated drugs, reducing their side effects. However, few liposomal formulations have demonstrated a significant advantage in therapeutic terms. Lipoplatin, a cisplatin formulation in Phase III, combines a reduction in the toxicity associated with an antitumor activity similar to the free drug. Thermosensitive or targeted liposomes for tumor therapy are also included in this review. Few articles about this strategy applied to platinum drugs can be found in the literature.

  6. Multimodality imaging demonstrates trafficking of liposomes preferentially to ischemic myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Lipinski, Michael J., E-mail: mjlipinski12@gmail.com [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States); Albelda, M. Teresa [GIBI2" 3" 0, Grupo de Investigación Biomédica en Imagen, IIS La Fe, Valencia (Spain); Frias, Juan C. [Departamento de Ciencias Biomédicas, Universidad CEU Cardenal Herrera, Valencia (Spain); Anderson, Stasia A. [Advanced Cardiovascular Imaging Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (United States); Luger, Dror; Westman, Peter C.; Escarcega, Ricardo O.; Hellinga, David G.; Waksman, Ron [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States); Arai, Andrew E. [Advanced Cardiovascular Imaging Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (United States); Epstein, Stephen E. [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States)

    2016-03-15

    Introduction: Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia–reperfusion murine myocardial infarction model. Methods: Mice underwent ischemia–reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24 h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging. Results: The mean size of the liposomes was 100 nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163 ± 31% vs. 13 ± 14%, p = 0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium. Conclusions: Liposomes traffic to the heart and preferentially home to regions of myocardial injury, enabling improved diagnosis of myocardial injury and could serve as a vehicle for drug delivery.

  7. Effectiveness of liposomal-N-acetylcysteine against LPS-induced lung injuries in rodents.

    Science.gov (United States)

    Mitsopoulos, Panagiotis; Omri, Abdelwahab; Alipour, Misagh; Vermeulen, Natasha; Smith, Milton G; Suntres, Zacharias E

    2008-11-03

    Acute lung injury (ALI) and its most severe form, the acute respiratory distress syndrome (ARDS) are frequent complications in critically ill patients and are responsible for significant morbidity and mortality. So far, experimental evidence supports the role of oxidants and oxidative injury in the pathogenesis of ALI/ARDS. In this study, the antioxidant effects of conventional N-acetylcysteine (NAC) and liposomally entrapped N-acetylcysteine (L-NAC) were evaluated in experimental animals challenged with lipopolysaccharide (LPS). Rats were pretreated with empty liposomes, NAC, or L-NAC (25mg/kg body weight, iv); 4h later were challenged with LPS (E. coli, LPS 0111:B4) and sacrificed 20h later. Challenge of saline (SAL)-pretreated animals with LPS resulted in lung injury as evidenced by increases in wet lung weight (edema), increases in lipid peroxidation (marker of oxidative stress), decreases of lung angiotensin-converting enzyme (ACE) (injury marker for pulmonary endothelial cells) and increases in the pro-inflammatory eicosanoids, thromboxane B(2) and leukotriene B(4). The LPS challenge also increased pulmonary myeloperoxidase activity and chloramine concentrations indicative of neutrophil infiltration and activation of the inflammatory response. Pretreatment of animals with L-NAC resulted in significant increases in the levels of non-protein thiols and NAC levels in lung homogenates (p<0.05) and bronchoalveolar lavage fluids (p<0.001), respectively. L-NAC was significantly (p<0.05) more effective than NAC or empty liposomes in attenuating the LPS-induced lung injuries as indicated by the aforementioned injury markers. Our results suggested that the delivery of NAC as a liposomal formulation improved its prophylactic effectiveness against LPS-induced lung injuries.

  8. 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...

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

    Science.gov (United States)

    Mota, Aline de Carvalho Varjão; de Freitas, Zaida Maria Faria; Ricci Júnior, Eduardo; Dellamora-Ortiz, Gisela Maria; Santos-Oliveira, Ralph; Ozzetti, Rafael Antonio; Vergnanini, André Luiz; Ribeiro, Vanessa Lira; Silva, Ronald Santos; dos Santos, Elisabete Pereira

    2013-01-01

    Solar radiation causes damage to human skin, and photoprotection is the main way to prevent these harmful effects. The development of sunscreen formulations containing nanosystems is of great interest in the pharmaceutical and cosmetic industries because of the many potential benefits. This study aimed to develop and evaluate an octyl methoxycinnamate (OMC) liposomal nanosystem (liposome/OMC) to obtain a sunscreen formulation with improved safety and efficacy by retaining OMC for longer on the stratum corneum. The liposome/OMC nanostructure obtained was tested for enzymatic hydrolysis with lipase from Rhizomucor miehei and biodistribution with liposomes labeled with technetium-99m. The liposome/OMC formulation was then incorporated in a gel formulation and tested for ocular irritation using the hen's egg test-chorio-allantoic membrane (HET-CAM) assay, in vitro and in vivo sun protection factor, in vitro release profile, skin biometrics, and in vivo tape stripping. The liposome/OMC nanosystem was not hydrolyzed from R. miehei by lipase. In the biodistribution assay, the liposome/OMC formulation labeled with technetium-99m had mainly deposited in the skin, while for OMC the main organ was the liver, showing that the liposome had higher affinity for the skin than OMC. The liposome/OMC formulation was classified as nonirritating in the HET-CAM test, indicating good histocompatibility. The formulation containing liposome/OMC had a higher in vivo solar photoprotection factor, but did not show increased water resistance. Inclusion in liposomes was able to slow down the release of OMC from the formulation, with a lower steady-state flux (3.9 ± 0.33 μg/cm(2)/hour) compared with the conventional formulation (6.3 ± 1.21 μg/cm(2)/hour). The stripping method showed increased uptake of OMC in the stratum corneum, giving an amount of 22.64 ± 7.55 μg/cm(2) of OMC, which was higher than the amount found for the conventional formulation (14.57 ± 2.30 μg/cm(2)). These results

  10. External beam radiotherapy synergizes 188Re-liposome against human esophageal cancer xenograft and modulates 188Re-liposome pharmacokinetics

    Science.gov (United States)

    Chang, Chih-Hsien; Liu, Shin-Yi; Chi, Chih-Wen; Yu, Hsiang-Lin; Chang, Tsui-Jung; Tsai, Tung-Hu; Lee, Te-Wei; Chen, Yu-Jen

    2015-01-01

    External beam radiotherapy (EBRT) treats gross tumors and local microscopic diseases. Radionuclide therapy by radioisotopes can eradicate tumors systemically. Rhenium 188 (188Re)-liposome, a nanoparticle undergoing clinical trials, emits gamma rays for imaging validation and beta rays for therapy, with biodistribution profiles preferential to tumors. We designed a combinatory treatment and examined its effects on human esophageal cancer xenografts, a malignancy with potential treatment resistance and poor prognosis. Human esophageal cancer cell lines BE-3 (adenocarcinoma) and CE81T/VGH (squamous cell carcinoma) were implanted and compared. The radiochemical purity of 188Re-liposome exceeded 95%. Molecular imaging by NanoSPECT/CT showed that BE-3, but not CE81T/VGH, xenografts could uptake the 188Re-liposome. The combination of EBRT and 188Re-liposome inhibited tumor regrowth greater than each treatment alone, as the tumor growth inhibition rate was 30% with EBRT, 25% with 188Re-liposome, and 53% with the combination treatment at 21 days postinjection. Combinatory treatment had no additive adverse effects and significant biological toxicities on white blood cell counts, body weight, or liver and renal functions. EBRT significantly enhanced the excretion of 188Re-liposome into feces and urine. In conclusion, the combination of EBRT with 188Re-liposome might be a potential treatment modality for esophageal cancer. PMID:26056445

  11. [Transfection of pEGFP-C2 in brain mediated by targeting liposome P-MMA-DOSPER].

    Science.gov (United States)

    Tang, Shaonian; Liu, Zhenhua; Zhao, Lianxu; Zou, Zhihao; Du, Mouxuan

    2008-10-01

    This research tried improving the specificity and efficiency of gene transfection in gene therapy and tried making the liposome a better gene transfer vector to brain by use of the monoclonal antibody (anti-Lex/SSEA-1)-mediated targeting of liposome. The derivatized monoclonal antibody was conjugated to the liposome DOSPER to form the targeting liposome P-MMA-DOSPER. Then, the pEGFP-C2 encapsulated in P-MMA-DOSPER or DOSPER was injected into the lateral ventricle of SD rats respectively, and the brains were taken for frosted slice 1, 3, 7 or 14 days later. The expression of GFP was observed under fluorescent microscope. There was a lot of expression of GFP around the lateral ventricle of rats in each group. But the indirect fluorescence antibody test showed the ratio of GFP+/nestin+ cells to nestin+ cells of every marking time point in the group of P-MMA-DOSPER was higher than the one in the group of DOSPER; the difference was found to be statistically significant (PMMA-DOSPER can permeat the ependyma and can transfer gene into the nerve stem cells in vivo safely and effectively.

  12. The antitumor activity of tumor-homing peptide-modified thermosensitive liposomes containing doxorubicin on MCF-7/ADR: in vitro and in vivo.

    Science.gov (United States)

    Wang, Chao; Wang, Xin; Zhong, Ting; Zhao, Yang; Zhang, Wei-Qiang; Ren, Wei; Huang, Dan; Zhang, Shuang; Guo, Yang; Yao, Xin; Tang, Yi-Qun; Zhang, Xuan; Zhang, Qiang

    2015-01-01

    Clotted plasma proteins are present on the walls of tumor vessels and in tumor stroma. Tumor-homing peptide Cys-Arg-Glu-Lys-Ala (CREKA) could recognize the clotted plasma proteins in tumor vessels. Thermosensitive liposomes could immediately release the encapsulated drug in the vasculature of the heated tumor. In this study, we designed a novel form of targeted thermosensitive liposomes, CREKA-modified lysolipid-containing thermosensitive liposomes (LTSLs), containing doxorubicin (DOX) (DOX-LTSL-CREKA), to investigate the hypothesis that DOX-LTSL-CREKA might target the clotted plasma proteins in tumor vessels as well as tumor stroma and then exhibit burst release of the encapsulated DOX at the heated tumor site. We also hypothesized that the high local drug concentration produced by these thermosensitive liposomes after local hyperthermia treatment will be useful for treatment of multidrug resistance. The multidrug-resistant human breast adenocarcinoma (MCF-7/ADR) cell line was chosen as a tumor cell model, and the targeting and immediate release characteristics of DOX-LTSL-CREKA were investigated in vitro and in vivo. Furthermore, the antitumor activity of DOX-LTSL-CREKA was evaluated in MCF-7/ADR tumor-bearing nude mice in vivo. The targeting effect of the CREKA-modified thermosensitive liposomes on the clotted plasma proteins was confirmed in our in vivo imaging and immunohistochemistry experiments. The burst release of this delivery system was observed in our in vitro temperature-triggered DOX release and flow cytometry analysis and also by confocal microscopy experiments. The antitumor activity of the DOX-LTSL-CREKA was confirmed in tumor-bearing nude mice in vivo. Our findings suggest that the combination of targeting the clotted plasma proteins in the tumor vessel wall as well as tumor stroma by using CREKA peptide and temperature-triggered drug release from liposomes by using thermosensitive liposomes offers an attractive strategy for chemotherapeutic drug

  13. Spontaneous Atraumatic Mediastinal Hemorrhage

    Directory of Open Access Journals (Sweden)

    Morkos Iskander BSc, BMBS, MRCS, PGCertMedEd

    2013-04-01

    Full Text Available Spontaneous atraumatic mediastinal hematomas are rare. We present a case of a previously fit and well middle-aged lady who presented with acute breathlessness and an increasing neck swelling and spontaneous neck bruising. On plain chest radiograph, widening of the mediastinum was noted. The bruising was later confirmed to be secondary to mediastinal hematoma. This life-threatening diagnostic conundrum was managed conservatively with a multidisciplinary team approach involving upper gastrointestinal and thoracic surgeons, gastroenterologists, radiologists, intensivists, and hematologists along with a variety of diagnostic modalities. A review of literature is also presented to help surgeons manage such challenging and complicated cases.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  16. 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.

  17. Recurrent spontaneous intracerebral hemorrhage associated with ...

    African Journals Online (AJOL)

    Spontaneous intracerebral hemorrhage (ICH) accounts for 15% of stroke cases in the US and Europe and up to 30% in Asian populations. Intracerebral hemorrhage is a relatively uncommon form of stroke-it causes only 10 to 15 percent of all strokes. It is more disabling and has a higher mortality rate than ischemic stroke, ...

  18. Spontaneous electric fields in solid films: spontelectrics

    DEFF Research Database (Denmark)

    Field, David; Plekan, Oksana; Cassidy, Andrew

    2013-01-01

    When dipolar gases are condensed at sufficiently low temperature onto a solid surface, they form films that may spontaneously exhibit electric fields in excess of 108V/m. This effect, called the ‘spontelectric effect’, was recently revealed using an instrument designed to measure scattering...

  19. [Analysis of parameters of serum concentration and pharmacokinetic of liposome and aqueous solution of toatal ginsenoside of ginseng stems and leaves in rats].

    Science.gov (United States)

    Zha, Lin; Zhao, Yan; Zhu, Hong-Yan; Cai, En-Bo; Liu, Shuang-Li; Yang, He; Zhao, Ying; Gao, Yu-Gang; Zhang, Lian-Xue

    2017-05-01

    The experiment was aimed to investigate the difference of plasma concentration and pharmacokinetic parameters between liposome and aqueous solution of toatal ginsenoside of ginseng stems and leaves in rats, such as ginsenosides Rg₁, Re, Rf, Rb₁, Rg₂, Rc, Rb₂, Rb₃, Rd. After intravenous injection of liposome and aqueous solution in rats, the blood was taken from the femoral vein to detect the plasma concentration of the above 9 ginsenoside monomers in different time points by using HPLC. The concentration-time curve was obtained and 3p97 pharmacokinetic software was used to get the pharmacokinetic parameters. After the intravenous injection of ginsenosides to rats, nine ginsenosides were detected in plasma. In general, among these ginsenosides, the peak time of the aqueous solution was between 0.05 to 0.083 3 h, and the serum concentration peak of liposome usually appeared after 0.5 h. After software fitting, the aqueous solution of ginsenoside monomers Rg₁, Re, Rf, Rg₂, Rc, Rd, Rb₃ was two-compartment model, and the liposomes were one-compartment model; aqueous solution and liposome of ginsenoside monomers Rb₁ were three-compartment model; aqueous solution of ginsenoside monomers Rb₂ was three-compartment model, and its liposome was one-compartment model. Area under the drug time curve (AUC) of these 9 kinds of saponin liposomes was larger than that of aqueous solution, and the retention time of the liposomes was longer than that of the aqueous solution; the removal rate was slower than that of the aqueous solution, and the half-life was longer than that of the water solution. The results from the experiment showed that by intravenous administration, the pharmacokinetic parameters of two formulations were significantly different from each other; the liposomes could not only remain the drug for a longer time in vivo, but also reduce the elimination rate and increase the treatment efficacy. As compared with the traditional dosage forms, the total

  20. Placing and shaping liposomes with reconfigurable DNA nanocages

    Science.gov (United States)

    Zhang, Zhao; Yang, Yang; Pincet, Frederic; C. Llaguno, Marc; Lin, Chenxiang

    2017-07-01

    The diverse structure and regulated deformation of lipid bilayer membranes are among a cell's most fascinating features. Artificial membrane-bound vesicles, known as liposomes, are versatile tools for modelling biological membranes and delivering foreign objects to cells. To fully mimic the complexity of cell membranes and optimize the efficiency of delivery vesicles, controlling liposome shape (both statically and dynamically) is of utmost importance. Here we report the assembly, arrangement and remodelling of liposomes with designer geometry: all of which are exquisitely controlled by a set of modular, reconfigurable DNA nanocages. Tubular and toroid shapes, among others, are transcribed from DNA cages to liposomes with high fidelity, giving rise to membrane curvatures present in cells yet previously difficult to construct in vitro. Moreover, the conformational changes of DNA cages drive membrane fusion and bending with predictable outcomes, opening up opportunities for the systematic study of membrane mechanics.

  1. Treatment of deep mycoses with liposomal amphotericin B.

    Science.gov (United States)

    Berenguer, J; Muñoz, P; Parras, F; Fernández-Baca, V; Hernández-Sampelayo, T; Bouza, E

    1994-06-01

    Amphotericin B is the mainstay of therapy of many deep mycoses, but its use is seriously hampered by dose-limiting nephrotoxicity. In this study a liposomal formulation of amphotericin B was administered to ten patients with proven deep mycoses: invasive aspergillosis (n = 4), deep candidiasis (n = 4) and zygomycosis (n = 2). The mean daily dosage of liposomal amphotericin B was 3.0 mg/kg (range 2.5 to 4 mg/kg), the mean total dosage of liposomal amphotericin B 2,781 mg (range 87 to 5,220 mg) and the mean duration of treatment 17 days (range 3 to 33 days). Treatment with liposomal amphotericin B was associated with little nephrotoxicity and an overall survival rate of 50%. The median increase of serum creatinine from baseline levels was 0.38 mg/dl (-1.2 to 2.6 mg/dl).

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

    Science.gov (United States)

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

    1988-01-01

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

  3. Detection of antimycolic acid antibodies by liposomal biosensors

    CSIR Research Space (South Africa)

    Lemmer, Yolandy

    2009-01-01

    Full Text Available Antibodies to mycolic acid (MA) antigens can be detected as surrogate markers of active tuberculosis (TB) with evanescent field biosensors where the lipid antigens are encapsulated in liposomes. Standard immunoassay such as ELISA, where the lipid...

  4. Liposomal prednisolone promotes macrophage lipotoxicity in experimental atherosclerosis

    NARCIS (Netherlands)

    van der Valk, F.M.; Schulte, D.M.; Meiler, S.; Tang, J.; Zheng, K.H.; van den Bossche, J.; Seijkens, T.; Laudes, M.; de Winther, M.; Lutgens, E.; Alaarg, Amr Muhmed Sabry Abdelhakeem; Metselaar, Josbert Maarten; Dallinga-Thie, G.M.; Mulder, W.J.M.; Stroes, Erik S.G.; Hamers, A.A.J.

    2016-01-01

    Atherosclerosis is a lipid-driven inflammatory disease, for which nanomedicinal interventions are under evaluation. Previously, we showed that liposomal nanoparticles loaded with prednisolone (LN-PLP) accumulated in plaque macrophages, however, induced proatherogenic effects in patients. Here, we

  5. Coiled coil driven membrane fusion between cyclodextrin vesicles and liposomes

    NARCIS (Netherlands)

    Versluis, Frank; Voskuhl, Jens; Vos, Jan; Friedrich, Heiner; Ravoo, Bart Jan; Bomans, Paul H H; Stuart, Marc C A; Sommerdijk, Nico A J M; Kros, Alexander

    2014-01-01

    Controlled fusion events between natural membranes composed of phospholipids with synthetic unnatural membranes will yield valuable fundamental information on the mechanism of membrane fusion. Here, fusion between vastly different phospholipid liposomes and cyclodextrin amphiphile based vesicles

  6. Spontaneous Appendicocutaneous Fistula I

    African Journals Online (AJOL)

    M T0k0de* MB, BS and. Dr 0. A. AWOj0bi+ FMCS (Nig). ABSTRACT. Ruptured appendicitis is not a common cause of spontaneous enterocutaneous fistula. A case of ruptured retrocaecal appendicitis presenting as an enterocutaneous fistula in a Nigerian woman is presented. The literature on this disorder is also reviewed.

  7. [Spontaneous bacterial peritonitis].

    Science.gov (United States)

    Strauss, Edna; Caly, Wanda Regina

    2003-01-01

    Spontaneous bacterial peritonitis occurs in 30% of patients with ascites due to cirrhosis leading to high morbidity and mortality rates. The pathogenesis of spontaneous bacterial peritonitis is related to altered host defenses observed in end-stage liver disease, overgrowth of microorganisms, and bacterial translocation from the intestinal lumen to mesenteric lymph nodes. Clinical manifestations vary from severe to slight or absent, demanding analysis of the ascitic fluid. The diagnosis is confirmed by a number of neutrophils over 250/mm3 associated or not to bacterial growth in culture of an ascites sample. Enterobacteriae prevail and Escherichia coli has been the most frequent bacterium reported. Mortality rates decreased markedly in the last two decades due to early diagnosis and prompt antibiotic treatment. Third generation intravenous cephalosporins are effective in 70% to 95% of the cases. Recurrence of spontaneous bacterial peritonitis is common and can be prevented by the continuous use of oral norfloxacin. The development of bacterial resistance demands the search for new options in the prophylaxis of spontaneous bacterial peritonitis; probiotics are a promising new approach, but deserve further evaluation. Short-term antibiotic prophylaxis is recommended for patients with cirrhosis and ascites shortly after an acute episode of gastrointestinal bleeding.

  8. EDITORIAL SPONTANEOUS BACTERIAL PERITONITIS ...

    African Journals Online (AJOL)

    hi-tech

    Spontaneous bacterial peritonitis (SBP) frequent]y occurs in patients with liver cirrhosis and ascites. It is defined as an infection of previously sterile ascitic fluid without any demonstrable intrabdominal source of infection. It is now internationally agreed that a polymorphonuclear (PMN) cell count in the ascitic fluid of over 250 ...

  9. Spontaneous dimensional reduction?

    Science.gov (United States)

    Carlip, Steven

    2012-10-01

    Over the past few years, evidence has begun to accumulate suggesting that spacetime may undergo a "spontaneous dimensional reduction" to two dimensions near the Planck scale. I review some of this evidence, and discuss the (still very speculative) proposal that the underlying mechanism may be related to short-distance focusing of light rays by quantum fluctuations.

  10. 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

  11. Optimization of liposomal topotecan for use in treating neuroblastoma.

    Science.gov (United States)

    Chernov, Lina; Deyell, Rebecca J; Anantha, Malathi; Dos Santos, Nancy; Gilabert-Oriol, Roger; Bally, Marcel B

    2017-06-01

    The purpose of this work was to develop an optimized liposomal formulation of topotecan for use in the treatment of patients with neuroblastoma. Drug exposure time studies were used to determine that topotecan (Hycamtin) exhibited great cytotoxic activity against SK-N-SH, IMR-32 and LAN-1 neuroblastoma human cell lines. Sphingomyelin (SM)/cholesterol (Chol) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/Chol liposomes were prepared using extrusion methods and then loaded with topotecan by pH gradient and copper-drug complexation. In vitro studies showed that SM/Chol liposomes retained topotecan significantly better than DSPC/Chol liposomes. Decreasing the drug-to-lipid ratio engendered significant increases in drug retention. Dose-range finding studies on NRG mice indicated that an optimized SM/Chol liposomal formulation of topotecan prepared with a final drug-to-lipid ratio of 0.025 (mol: mol) was better tolerated than the previously described DSPC/Chol topotecan formulation. Pharmacokinetic studies showed that the optimized SM/Chol liposomal topotecan exhibited a 10-fold increase in plasma half-life and a 1000-fold increase in AUC 0-24 h when compared with Hycamtin administered at equivalent doses (5 mg/kg). In contrast to the great extension in exposure time, SM/Chol liposomal topotecan increased the life span of mice with established LAN-1 neuroblastoma tumors only modestly in a subcutaneous and systemic model. The extension in exposure time may still not be sufficient and the formulation may require further optimization. In the future, liposomal topotecan will be assessed in combination with high-dose radiotherapy such as 131 I-metaiodobenzylguanidine, and immunotherapy treatment modalities currently used in neuroblastoma therapy. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  12. 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)....

  13. Oral delivery of vancomycin by tetraether lipid liposomes.

    Science.gov (United States)

    Uhl, Philipp; Pantze, Silvia; Storck, Philip; Parmentier, Johannes; Witzigmann, Dominik; Hofhaus, Götz; Huwyler, Jörg; Mier, Walter; Fricker, Gert

    2017-10-15

    Despite the outstanding progress in modern medicine, the oral delivery of peptide drugs is limited until today due to their instability in the gastrointestinal tract and low mucosa penetration. To overcome these hurdles, liposomes containing the specific tetraether lipid GCTE (glycerylcaldityltetraether lipid) were examined. For this purpose, the glycopeptide antibiotic vancomycin was used as model substance and liposomes were prepared by DAC (dual assymetric centrifugation). These liposomes showed a size and polydispersity index comparable to standard liposomes. A high encapsulation efficiency of 58.53±1.76% of the peptide drug vancomycin could be obtained as detected by HPLC. FCS analysis showed that in average each liposome contains 30 molecules of vancomycin. TEM and Cryo-EM micrographs verified the size and lamellarity of the liposomal formulations. Cytotoxicity tests in Caco-2 cells showed no significant cytotoxicity for all liposomal concentrations tested, indicating the good tolerability of these formulations. Furthermore, the use of sucrose as lyoprotector enabled the long term storage of the liposomal formulation for at least three months. The potency of this drug delivery system could be proven in an animal model using Wistar rats. One hour after oral application, 4.82±0.56% of the administered dose of vancomycin could be found in the blood as detected by immunoassay measurements. This transport did also not affect the integrity of the peptide as verified by immunoassay measurements. In combination with long term storage stability, this formulation appears to be a promising delivery system for oral application of peptide drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Gasselhuber, Astrid; Dreher, Matthew R; Rattay, Frank; Wood, Bradford J; 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 bolus at a dose of 9 mg/kg. For TSL, we assumed locally triggered release due to hyperthermia for 30 min. Drug concentrations were determined in systemic plasma, aggregate body tissue, cardiac tissue, tumor plasma, tumor interstitial space, and tumor cells. All compartments were assumed perfectly mixed, and represented by ordinary differential equations. Contribution of liposomal extravasation was negligible in the case of TSL-i, but was the major delivery mechanism for Stealth-DOX and for TSL-e. The dominant delivery mechanism for TSL-i was release within the tumor plasma compartment with subsequent tissue- and cell uptake of released DOX. Maximum intracellular tumor drug concentrations for Free-DOX, Stealth-DOX, TSL-i, and TSL-e were 3.4, 0.4, 100.6, and 15.9 µg/g, respectively. TSL-i and TSL-e allowed for high local tumor drug concentrations with reduced systemic exposure compared to Free-DOX. While Stealth-DOX resulted in high tumor tissue concentrations compared to Free-DOX, only a small fraction was bioavailable, resulting in little cellular uptake. Consistent with clinical data, Stealth-DOX resulted in similar tumor intracellular concentrations as Free-DOX, but with reduced systemic exposure. Optimal release time constants for maximum cellular uptake for Stealth-DOX, TSL-e, and TSL-i were 45 min, 11 min, and constants were shorter for MDR cells, with ∼4 min for Stealth-DOX and for TSL-e. Tissue concentrations correlated well quantitatively with a prior in-vivo study

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

    Directory of Open Access Journals (Sweden)

    Astrid Gasselhuber

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

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

    DEFF Research Database (Denmark)

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

    2001-01-01

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

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

    International Nuclear Information System (INIS)

    Haefeli, U.

    1989-01-01

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

  18. Iron complexation to histone deacetylase inhibitors SAHA and LAQ824 in PEGylated liposomes can considerably improve pharmacokinetics in rats.

    Science.gov (United States)

    Wang, Yan; Tu, Sheng; Steffen, Dana; Xiong, May

    2014-01-01

    The formulation of histone deacetylase inhibitors (HDACi) is challenging due to poor water solubility and rapid elimination of drugs in vivo. This study investigated the effects of complexing iron (Fe3+) to the HDACi suberoylanilide hydroxamic acid (SAHA) and LAQ824 (LAQ) prior to their encapsulation into PEGylated liposomes, and investigated whether this technique could improve drug solubility, in vitro release and in vivo pharmacokinetic (PK) properties. METHODS. The reaction stoichiometry, binding constants and solubility were measured for Fe complexes of SAHA and LAQ. The complexes were passively encapsulated into PEGylated liposomes and characterized by size distribution, zeta-potential, encapsulation efficiency (EE), and in vitro drug release studies. PC-3 cells were used to verify the in vitro anticancer activity of the formulations. In vivo pharmacokinetic properties of liposomal LAQ-Fe (L-LAQ-Fe) was evaluated in rats. RESULTS. SAHA and LAQ form complexes with Fe at 1:1 stoichiometric ratio, with a binding constant on the order of 104 M-1. Fe complexation improved the aqueous solubility and the liposomal encapsulation efficiency of SAHA and LAQ (29-35% EE, final drug concentration > 1 mM). Liposomal encapsulated complexes (L-HDACi-Fe) exhibited sustained in vitro release properties compared to L-HDACi but cytotoxicity on PC-3 cells was comparable to free drugs. The PK of L-LAQ-Fe revealed 15-fold improvement in the plasma t1/2 (12.11 h)and 211-fold improvement in the AUC∞ (105.7 µg·h/ml) compared to free LAQ (0.79 h, 0.5 µg·h/ml). Similarly, the plasma t1/2 of Fe was determined to be 11.83 h in a separate experiment using radioactive Fe-59. The majority of Fe-59 activity was found in liver and spleen of rats and correlates with liposomal uptake by the mononuclear phagocyte system. CONCLUSIONS. We have demonstrated that encapsulation of Fe complexes of HDACi into PEGylated liposomes can improve overall drug aqueous solubility, in vitro release and in

  19. Technological and Theoretical Aspects for Testing Electroporation on Liposomes

    Directory of Open Access Journals (Sweden)

    Agnese Denzi

    2017-01-01

    Full Text Available Recently, the use of nanometer liposomes as nanocarriers in drug delivery systems mediated by nanoelectroporation has been proposed. This technique takes advantage of the possibility of simultaneously electroporating liposomes and cell membrane with 10-nanosecond pulsed electric fields (nsPEF facilitating the release of the drug from the liposomes and at the same time its uptake by the cells. In this paper the design and characterization of a 10 nsPEF exposure system is presented, for liposomes electroporation purposes. The design and the characterization of the applicator have been carried out choosing an electroporation cuvette with 1 mm gap between the electrodes. The structure efficiency has been evaluated at different experimental conditions by changing the solution conductivity from 0.25 to 1.6 S/m. With the aim to analyze the influence of device performances on the liposomes electroporation, microdosimetric simulations have been performed considering liposomes of 200 and 400 nm of dimension with different inner and outer conductivity (from 0.05 to 1.6 S/m in order to identify the voltage needed for their poration.

  20. The Role of Liposomal Bupivacaine in Value-Based Care.

    Science.gov (United States)

    Iorio, Richard

    Multimodal pain control strategies are crucial in reducing opioid use and delivering effective pain management to facilitate improved surgical outcomes. The utility of liposomal bupivacaine in enabling effective pain control in multimodal strategies has been demonstrated in several studies, but others have found the value of liposomal bupivacaine in such approaches to be insignificant. At New York University Langone Medical Center, liposomal bupivacaine injection and femoral nerve block were compared in their delivery of efficacious and cost-effective multimodal analgesia among patients undergoing total joint arthroplasty (TJA). Retrospective analysis revealed that including liposomal bupivacaine in a multimodal pain control protocol for TJA resulted in improved quality and efficiency metrics, decreased narcotic use, and faster mobilization, all relative to femoral nerve block, and without a significant increase in admission costs. In addition, liposomal bupivacaine use was associated with elimination of the need for patient-controlled analgesia in TJA. Thus, at Langone Medical Center, the introduction of liposomal bupivacaine to TJA has been instrumental in achieving adequate pain control, delivering high-level quality of care, and controlling costs.

  1. The antimicrobial activity of liposomal lauric acids against Propionibacterium acnes.

    Science.gov (United States)

    Yang, Darren; Pornpattananangkul, Dissaya; Nakatsuji, Teruaki; Chan, Michael; Carson, Dennis; Huang, Chun-Ming; Zhang, Liangfang

    2009-10-01

    This study evaluated the antimicrobial activity of lauric acid (LA) and its liposomal derivatives against Propionibacterium acnes (P. acnes), the bacterium that promotes inflammatory acne. First, the antimicrobial study of three free fatty acids (lauric acid, palmitic acid and oleic acid) demonstrated that LA gives the strongest bactericidal activity against P. acnes. However, a setback of using LA as a potential treatment for inflammatory acne is its poor water solubility. Then the LA was incorporated into a liposome formulation to aid its delivery to P. acnes. It was demonstrated that the antimicrobial activity of LA was not only well maintained in its liposomal derivatives but also enhanced at low LA concentration. In addition, the antimicrobial activity of LA-loaded liposomes (LipoLA) mainly depended on the LA loading concentration per single liposomes. Further study found that the LipoLA could fuse with the membranes of P. acnes and release the carried LA directly into the bacterial membranes, thereby killing the bacteria effectively. Since LA is a natural compound that is the main acid in coconut oil and also resides in human breast milk and liposomes have been successfully and widely applied as a drug delivery vehicle in the clinic, the LipoLA developed in this work holds great potential of becoming an innate, safe and effective therapeutic medication for acne vulgaris and other P. acnes associated diseases.

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

    Directory of Open Access Journals (Sweden)

    Singh S

    2016-04-01

    potential of -22.4 mV; the entrapment efficiencies of the selected formulation was found to be 79.71%±0.27%. All formulations in the form of a gel were evaluated for physicochemical properties and were found to be homogeneous with no grittiness, and the pH of all formulations was found to be neutral. The optimized selected elastic liposomal formulation followed the Higuchi equation and Fickian diffusion and released the drug for a period of 24 hours. The overall results provide much promise for the continued investigation of deformable vesicles as transdermal drug carriers. Keywords: elastic liposome, skin delivery, occlusion, hydration-gradient, hydrogel

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

    Science.gov (United States)

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

    2016-01-01

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

  4. Spontaneous generation in medieval Jewish philosophy and theology.

    Science.gov (United States)

    Gaziel, Ahuva

    2012-01-01

    The concept of life forms emerging from inanimate matter--spontaneous generation--was widely accepted until the nineteenth century. Several medieval Jewish scholars acknowledged this scientific theory in their philosophical and religious contemplations. Quite interestingly, it served to reinforce diverse, or even opposite, theological conclusions. One approach excluded spontaneously-generated living beings form the biblical account of creation or the story of the Deluge. Underlying this view is an understanding that organisms that generate spontaneously evolve continuously in nature and, therefore, do not require divine intervention in their formation or survival during disastrous events. This naturalistic position reduces the miraculous dimension of reality. Others were of the opinion that spontaneous generation is one of the extraordinary marvels exhibited in this world and, accordingly, this interpretation served to accentuate the divine aspect of nature. References to spontaneous generation also appear in legal writings, influencing practical applications such as dietary laws and actions forbidden on the Sabbath.

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

    Directory of Open Access Journals (Sweden)

    Eliot. P. Botosoa

    2011-01-01

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

  6. Multilamellar liposomes entrapping aminosilane-modified maghemite nanoparticles: "magnetonions".

    Science.gov (United States)

    Meyre, Marie-Edith; Clérac, Rodolphe; Mornet, Stéphane; Duguet, Etienne; Dole, François; Nallet, Frédéric; Lambert, Olivier; Trépout, Sylvain; Faure, Chrystel

    2010-10-21

    4.6 nm-sized aminosilane-modified maghemite (γ-Fe(2)O(3)) nanoparticles (aMNPs) were synthesized and encapsulated into onion-type multilamellar vesicles of soybean phosphatidylcholine (90%mol) and monoolein (10%mol). The magnetic multilamellar vesicles were obtained by shearing lipids with an aqueous dispersion of the preformed aMNPs (ferrofluid). The influence of ferrofluid concentration on the stability of the constitutive lamellar phase and the resulting dispersed onions was analyzed by small-angle X-ray diffraction (SAXD) and cryo-TEM imaging, respectively. When [Fe(III)] liposomes were found. The deduced aMNP-to-onion ratio increased with ferrofluid concentration before reaching a maximal value of ca. 45 as confirmed by cryo-TEM imaging. When [Fe(III)] >60 mM, uni- or oligolamellar vesicles in addition to onions formed, probably because of a two-phase separation between an aMNP-rich phase and an aMNP-containing lamellar phase as revealed by SAXD.

  7. Peptide-Mediated Liposome Fusion: The Effect of Anchor Positioning

    Directory of Open Access Journals (Sweden)

    Niek S. A. Crone

    2018-01-01

    Full Text Available A minimal model system for membrane fusion, comprising two complementary peptides dubbed “E” and “K” joined to a cholesterol anchor via a polyethyleneglycol spacer, has previously been developed in our group. This system promotes the fusion of large unilamellar vesicles and facilitates liposome-cell fusion both in vitro and in vivo. Whilst several aspects of the system have previously been investigated to provide an insight as to how fusion is facilitated, anchor positioning has not yet been considered. In this study, the effects of placing the anchor at either the N-terminus or in the center of the peptide are investigated using a combination of circular dichroism spectroscopy, dynamic light scattering, and fluorescence assays. It was discovered that anchoring the “K” peptide in the center of the sequence had no effect on its structure, its ability to interact with membranes, or its ability to promote fusion, whereas anchoring the ‘E’ peptide in the middle of the sequence dramatically decreases fusion efficiency. We postulate that anchoring the ‘E’ peptide in the middle of the sequence disrupts its ability to form homodimers with peptides on the same membrane, leading to aggregation and content leakage.

  8. Spontaneous healing of spontaneous coronary artery dissection.

    Science.gov (United States)

    Almafragi, Amar; Convens, Carl; Heuvel, Paul Van Den

    2010-01-01

    Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome and sudden cardiac death. It should be suspected in every healthy young woman without cardiac risk factors, especially during the peripartum or postpartum periods. It is important to check for a history of drug abuse, collagen vascular disease or blunt trauma of the chest. Coronary angiography is essential for diagnosis and early management. We wonder whether thrombolysis might aggravate coronary dissection. All types of treatment (medical therapy, percutaneous intervention or surgery) improve the prognosis without affecting survival times if used appropriately according to the clinical stability and the angiographic features of the involved coronary arteries. Prompt recognition and targeted treatment improve outcomes. We report a case of SCAD in a young female free of traditional cardiovascular risk factors, who presented six hours after thrombolysis for ST elevation myocardial infarction. Coronary angiography showed a dissection of the left anterior descending and immediate branch. She had successful coronary artery bypass grafting, with complete healing of left anterior descending dissection.

  9. Spontaneous spinal epidural abscess.

    LENUS (Irish Health Repository)

    Ellanti, P

    2011-10-01

    Spinal epidural abscess is an uncommon entity, the frequency of which is increasing. They occur spontaneously or as a complication of intervention. The classical triad of fever, back pain and neurological symptoms are not always present. High index of suspicion is key to diagnosis. Any delay in diagnosis and treatment can have significant neurological consequences. We present the case of a previously well man with a one month history of back pain resulting from an epidural abscess.

  10. POSSIBILITY TO APPLY LIPOSOMAL ALPHA-2B INTERFERON FOR THE PREVENTION OF FLU AND OTHER ACUTE RESPIRATORY INFECTIONS

    Directory of Open Access Journals (Sweden)

    M.K. Erofeeva

    2007-01-01

    Full Text Available Within recent years, a special attention has been paid to the nonspecific prevention of the acute respiratory disease related to the increase of the activity of the natural mechanisms for antiviral protection. The application of the liposomal forms of the different medications contributes to the directed transportation of the biodegraded protein substances. A special interest is aroused by the opportunity to orally apply protein medications, as their injection forms quickly degrade in the stomach. New Russian liposomal recombinant alphac2b interferon has antiviral, immuno-modulating and interferonogenic activity. The work demonstrates experience of the oral application form of the liposomal medication of recombinant alphac2b interferon — reaferoncesclipint for the extra prevention of flu and other acute respiratory infections among children. The application of this medication to prevent flu and acute respiratory infections in the dose of 250,000 Ме twice a week for the 4 weeks' period proved to be efficient within the group of the preschool children (aged between 7–10 years old and manifested itself in the reduction of the flu and acute respiratory infections recurrence.Key words: flu, prevention, efficiency index, interferon.

  11. Etoposide incorporated into camel milk phospholipids liposomes shows increased activity against fibrosarcoma in a mouse model.

    Science.gov (United States)

    Maswadeh, Hamzah M; Aljarbou, Ahmad N; Alorainy, Mohammed S; Alsharidah, Mansour S; Khan, Masood A

    2015-01-01

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

  12. Encapsulation of phytosterols and phytosterol esters in liposomes made with soy phospholipids by high pressure homogenization.

    Science.gov (United States)

    Wang, Fan C; Acevedo, Nuria; Marangoni, Alejandro G

    2017-11-15

    Phytosterols and phytosterol esters were encapsulated within large unilamellar liposomes prepared with soy phospholipids using a microfluidizer. The average particle diameter of these liposomal vesicles increased with increasing amounts of encapsulated phytosterols, especially with increasing free sterol content. The phytosterol content, liposomal particle size, and phytosterol encapsulation efficiency started to plateau when liposomes were prepared with MOPS buffer dispersions that contained 50 mg ml -1 soy phospholipid and more than 4% phytosterol blend, suggesting the saturation of phytosterol encapsulation. We proposed an encapsulation mechanism of free sterols and phytosterol esters in liposomes, where free sterols were mainly encapsulated within the lumen of these liposomes as crystals, and sterol esters and some free sterols were incorporated within the phospholipid bilayer of the liposomal membrane. The results from this work could provide the pharmaceutical and nutraceutical industries a practical method to produce loaded liposomes using inexpensive phospholipid mixtures for the delivery of bioactive ingredients.

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

    Directory of Open Access Journals (Sweden)

    Hamzah M. Maswadeh

    2015-01-01

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

  14. 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 formulat...

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

    DEFF Research Database (Denmark)

    Parmentier, Johannes; Thomas, Nicky; Müllertz, Anette

    2012-01-01

    Liposomes are generally well tolerated drug delivery systems with a potential use for the oral route. However, little is known about the fate of liposomes during exposure to the conditions in the gastro-intestinal tract (GIT). To gain a better understanding of liposome stability in the intestine,...... to other lipid based delivery systems for the oral delivery of poorly soluble drugs......., a dynamic in vitro lipolysis model, which so far has only been used for the in vitro characterisation of other lipid-based drug delivery systems, was applied to different liposomal formulations. Liposome size and phospholipid (PL) digestion were determined as two markers for liposome stability. In addition...... lipolysis, the lipids exhibited a higher stability compared to SPC and only 30% of the PLs were digested. No direct correlation between liposome integrity assessed by vesicle size and PL digestion was observed. Danazol content in the liposomes was around 5% (mol/mol danazol/total lipid) and hardly any...

  16. Histopathologic Study Following Administration of Liposome-Encapsulated Hemoglobin in the Normovolemic Rat

    National Research Council Canada - National Science Library

    Rudolph, Alan

    1995-01-01

    ... bovine hemoglobin in the normovolemic rat. We have also examined the administration of the liposome vehicle, tetrameric bovine hemoglobin, and liposome encapsulated bovine hemoglobin that had been lyophilized with 300 mM trehalose...

  17. 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.; van Bloois, L.; Trautwein, C.; Lammers, Twan Gerardus Gertudis Maria; 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

  18. 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)

  19. Characterization of Annexin V Fusion with the Superfolder GFP in Liposomes Binding and Apoptosis Detection.

    Science.gov (United States)

    Abbady, Abdul Qader; Twair, Aya; Ali, Bouthaina; Murad, Hossam

    2017-01-01

    Programed cell death is a critical and unavoidable part of life. One of the most widely used markers for dying cells, by apoptosis or pyroptosis, is the redistribution of phosphatidylserine (PS) from the inner to the outer plasma membrane leaflet. Annexin V protein is a sensitive and specific probe to mark this event because of its high affinity to the exposed PS. Beyond that, annexin V can bind to any PS-containing phospholipid bilayer of almost all tiny forms of membranous vesicles like blood platelets, exosomes, or even nanostructured liposomes. In this work, recombinant human annexin V was produced as a fusion with a highly fluorescent superfolder derivative of the green fluorescent protein ( sf GFP) in Escherichia coli . The fusion protein( sf GFP-ANXV, 64 kDa), annexin V (ANXV, 40 kDa), and sf GFP (27 kDa) were separately produced after cloning their encoding genes in pRSET plasmid, and all proteins were expressed in a soluble form, then purified in high yields because of their N -terminal 6× His tag (~150 mg of pure protein per 1 L culture). Superiority of this fluorescent fusion protein over fluorescein-conjugated annexin V was demonstrated in binding to phospholipids (and their liposomes), prepared from natural sources (soya bean and egg yolk) that have different content of PS, by using different methods including ELISA, dot-blotting, surface plasmon resonance, and flow cytometry. We also applied fluorescent annexin V in the detection of apoptotic cells by flow cytometry and fluorescent microscopy. Interestingly, sf GFP-ANXV fusion was more sensitive to early apoptotic stressed HeLa cells than fluorescein-conjugated-ANXV. This highly expressed and functional sf GFP-ANXV fusion protein provides a promising ready-to-use molecular tool for quantifying liposomes (or similarly exosomes) and detecting apoptosis in cells.

  20. Structural characterization of photopolymerizable binary liposomes containing diacetylenic and saturated phospholipids.

    Science.gov (United States)

    Temprana, C Facundo; Duarte, Evandro L; Taira, M Cristina; Lamy, M Teresa; del Valle Alonso, Silvia

    2010-06-15

    The use of liposomes to encapsulate materials has received widespread attention for drug delivery, transfection, diagnostic reagent, and as immunoadjuvants. Phospholipid polymers form a new class of biomaterials with many potential applications in medicine and research. Of interest are polymeric phospholipids containing a diacetylene moiety along their acyl chain since these kinds of lipids can be polymerized by Ultra-Violet (UV) irradiation to form chains of covalently linked lipids in the bilayer. In particular the diacetylenic phosphatidylcholine 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) can form intermolecular cross-linking through the diacetylenic group to produce a conjugated polymer within the hydrocarbon region of the bilayer. As knowledge of liposome structures is certainly fundamental for system design improvement for new and better applications, this work focuses on the structural properties of polymerized DC8,9PC:1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes. Liposomes containing mixtures of DC8,9PC and DMPC, at different molar ratios, and exposed to different polymerization cycles, were studied through the analysis of the electron spin resonance (ESR) spectra of a spin label incorporated into the bilayer, and the calorimetric data obtained from differential scanning calorimetry (DSC) studies. Upon irradiation, if all lipids had been polymerized, no gel-fluid transition would be expected. However, even samples that went through 20 cycles of UV irradiation presented a DSC band, showing that around 80% of the DC8,9PC molecules were not polymerized. Both DSC and ESR indicated that the two different lipids scarcely mix at low temperatures, however few molecules of DMPC are present in DC8,9PC rich domains and vice versa. UV irradiation was found to affect the gel-fluid transition of both DMPC and DC8,9PC rich regions, indicating the presence of polymeric units of DC8,9PC in both areas. A model explaining lipids

  1. Label free and high specific detection of mercury ions based on silver nano-liposome.

    Science.gov (United States)

    Priyadarshini, Eepsita; Pradhan, Nilotpala; Pradhan, Arun K; Pradhan, Pallavi

    2016-06-15

    Herein, we report an eco-friendly, mild and one-pot approach for synthesis of silver nanoparticles via a lipopeptide biosurfactant - CHBS. The biosurfactant forms liposome vesicles when dispersed in an aqueous medium. The amino acid groups of the biosurfactant assists in the reduction of Ag(+) ions leading to the production of homogeneous silver nanoparticles, encapsulated within the liposome vesicle, as confirmed from TEM analysis. Rate of synthesis and size of particle were greatly dependent on pH and reaction temperature. Kinetic analysis suggests the involvement of an autocatalytic reaction and the observed rate constant (kobs) was found to decrease with temperature, suggesting faster reaction with increasing temperature. Furthermore, the silver nanoparticles served as excellent probes for highly selective and sensitive recognition of Hg(2+) ions. Interaction with Hg(2+) ions results in an immediate change in colour of nanoparticle solution form brownish red to milky white. With increasing Hg(2+) ions concentration, a gradual disappearance of SPR peak was observed. A linear relationship (A420/660) with an R(2) value of 0.97 was observed in the range of 20 to 100ppm Hg(2+) concentration. Hg(2+) ions are reduced to their elemental forms which thereby interact with the vesicles, leading to aggregation and precipitation of particles. The detection method avoids the need of functionalizing ligands and favours Hg(2+) detection in aqueous samples by visible range spectrophotometry and hence can be used for simple and rapid analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Nanoparticle-Stabilized Liposomes for pH-Responsive Gastric Drug Delivery

    OpenAIRE

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

    2013-01-01

    We report a novel pH-responsive gold nanoparticle-stabilized liposome system for gastric antimicrobial delivery. By adsorbing small chitosan-modified gold nanoparticles (diameter ~ 10 nm) onto the outer surface of negatively charged phospholipid liposomes (diameter ~ 75 nm), we show that at gastric pH the liposomes have excellent stability with limited fusion ability and negligible cargo releases. However when the stabilized liposomes are present in an environment with neutral pH, the gold st...

  3. In vitro and in vivo aspects of N-acyl-phosphatidylethanolamine-containing liposomes

    DEFF Research Database (Denmark)

    Vermehren, C.; Clausen-Beck, B.; Frøkjær, S.

    2003-01-01

    during storage for 5 weeks. Determination of T for NAPE-liposomes showed increasing values of T by increasing percentage of NAPE in the liposomal bilayer, due to the higher T of NAPE compared to phosphatidylcholine. Blood-clearance studies showed an initial increase in blood-circulation of liposomes...

  4. Detection of DNA hybridization on a liposome surface using ultrasound velocimetry and turbidimetry methods.

    Science.gov (United States)

    Hianik, Tibor; Rybar, Peter; Andreev, Sergej Yu; Oretskaya, Tatiana S; Vadgama, Pankaj

    2004-08-02

    19-mer oligonucleotides with oleylamine tethered at 3' and 5' terminal, respectively, were incorporated into unilamellar liposomes of dioleoylphosphatidylcholine (DOPC). Addition of complementary nucleotide resulted in hybridization with oligonucleotides located on different liposomes and caused liposome aggregation. Significant changes of sound velocimetry and turbidity were readily observed at 10 nM concentration of the complementary chain.

  5. A stimuli responsive liposome loaded hydrogel provides flexible on-demand release of therapeutic agents

    NARCIS (Netherlands)

    O'Neill, Hugh S.; Herron, Caroline C.; Hastings, Conn L.; Deckers, Roel; Lopez Noriega, Adolfo; Kelly, Helena M.; Hennink, Wim E.; McDonnell, Ciarán O.; O'Brien, Fergal J.; Ruiz-Hernández, Eduardo; Duffy, Garry P.

    2017-01-01

    Lysolipid-based thermosensitive liposomes (LTSL) embedded in a chitosan-based thermoresponsive hydrogel matrix (denoted Lipogel) represents a novel approach for the spatiotemporal release of therapeutic agents. The entrapment of drug-loaded liposomes in an injectable hydrogel permits local liposome

  6. Physicochemical properties of extruded and non-extruded liposomes containing the hydrophobic drug dexamethasone.

    Science.gov (United States)

    Bhardwaj, Upkar; Burgess, Diane J

    2010-03-30

    The physicochemical and release properties of non-extruded 'multilamellar' and small sonicated and extruded 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) liposomes containing hydrophobic drug dexamethasone were investigated. Non-extruded liposomes had similar diameter, however dexamethasone encapsulation decreased with increase in lipid chain length. Dexamethasone destabilized the liposome membranes as indicated by decrease in enthalpy and increase in the peak width of the main transition. Based on calorimetric analysis, it appeared that dexamethasone and cholesterol were heterogeneously distributed in the non-extruded liposomes. Sonication and extrusion reduced the diameter (DSPC>DPPC>DMPC) and decreased drug encapsulation (approximately 50%). Cholesterol incorporation decreased drug encapsulation in both extruded and non-extruded DMPC liposomes which appeared to be due to structural similarities between cholesterol and dexamethasone. Incorporation of dexamethasone and cholesterol in the same DMPC liposomes caused a marked perturbation in the phase transition. Dexamethasone release from extruded liposomes was fast, while non-extruded liposomes showed slower release. Release was fastest from DMPC liposomes and slowest from liposomes of high phase transition lipid DSPC. Incorporation of cholesterol did not decrease release from DMPC liposomes. These results indicated that change in the physicochemical properties and the phase transition behavior of liposomes, due to processing as well as incorporation of hydrophobic drug dexamethasone, changed their release properties. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  7. Poly(amino acid)s: next-generation coatings for long-circulating liposomes

    NARCIS (Netherlands)

    Romberg, B.

    2007-01-01

    Incorporation of a lipid conjugate of a water-soluble polymer into liposomes can reduce the adhesion of plasma proteins that would otherwise cause rapid recognition and removal of the liposomes by phagocytes. Such polymer-coated liposomes show prolonged circulation property and passive targeting to

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

    Science.gov (United States)

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

    2017-05-01

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

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

    Directory of Open Access Journals (Sweden)

    de Carvalho Varjão Mota A

    2013-12-01

    Full Text Available Aline de Carvalho Varjão Mota,1 Zaida Maria Faria de Freitas,1 Eduardo Ricci Júnior,1 Gisela Maria Dellamora-Ortiz,1 Ralph Santos-Oliveira,2 Rafael Antonio Ozzetti,3 André Luiz Vergnanini,3 Vanessa Lira Ribeiro,4 Ronald Santos Silva,4 Elisabete Pereira dos Santos11Faculty of Pharmacy, Federal University of Rio de Janeiro, 2Nuclear Engineering Institute, National Nuclear Energy Commission, 3Allergisa Dermatocosmetic Research, University of Campinas, São Paulo, 4Pharmacology and Toxicology Department, National Insitute of Quality Control in Health, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilAbstract: Solar radiation causes damage to human skin, and photoprotection is the main way to prevent these harmful effects. The development of sunscreen formulations containing nanosystems is of great interest in the pharmaceutical and cosmetic industries because of the many potential benefits. This study aimed to develop and evaluate an octyl methoxycinnamate (OMC liposomal nanosystem (liposome/OMC to obtain a sunscreen formulation with improved safety and efficacy by retaining OMC for longer on the stratum corneum.Methods: The liposome/OMC nanostructure obtained was tested for enzymatic hydrolysis with lipase from Rhizomucor miehei and biodistribution with liposomes labeled with technetium-99m. The liposome/OMC formulation was then incorporated in a gel formulation and tested for ocular irritation using the hen’s egg test-chorio-allantoic membrane (HET-CAM assay, in vitro and in vivo sun protection factor, in vitro release profile, skin biometrics, and in vivo tape stripping.Results: The liposome/OMC nanosystem was not hydrolyzed from R. miehei by lipase. In the biodistribution assay, the liposome/OMC formulation labeled with technetium-99m had mainly deposited in the skin, while for OMC the main organ was the liver, showing that the liposome had higher affinity for the skin than OMC. The liposome/OMC formulation was classified as nonirritating in

  10. Development of risperidone liposomes for brain targeting through intranasal route.

    Science.gov (United States)

    Narayan, Reema; Singh, Mohan; Ranjan, OmPrakash; Nayak, Yogendra; Garg, Sanjay; Shavi, Gopal V; Nayak, Usha Y

    2016-10-15

    The present paper is aimed at development of functionalized risperidone liposomes for brain targeting through nasal route for effective therapeutic management of schizophrenia. The risperidone liposomes were prepared by thin film hydration method. Various parameters such as lipid ratio and lipid to drug ratio were optimized by using Design-Expert(®) Software to obtain high entrapment with minimum vesicle size. The surface of the optimized liposomes was modified by coating stearylamine and MPEG-DSPE for enhanced penetration to the brain. The formulations were evaluated for vesicle size, zeta potential, and entrapment efficiency. The morphology was studied by Transmission Electron Microscopy (TEM). In vivo efficacy was assessed by performing pharmacokinetic study in Wistar albino rats following intranasal administration of the formulations in comparison to intravenous bolus administration of pure drug. The mean vesicle size of optimized liposomes ranged from 90 to 100nm with low polydispersity index (risperidone into the brain than plasma. High brain targeting efficiency index for LP-16 indicating preferential transport of the drug to brain. The study demonstrated successful formulation of surface modified risperidone liposomes for nasal delivery with brain targeting potential. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Chahar P

    2012-08-01

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

  12. Polymer coated mucoadhesive liposomes intended for the management of xerostomia.

    Science.gov (United States)

    Adamczak, Małgorzata I; Martinsen, Ørjan G; Smistad, Gro; Hiorth, Marianne

    2017-07-15

    The aim of this work was to prepare and test different pharmaceutical formulations in respect of their potential in relieving dry mouth symptom. Since many of the products available on the market provide only temporary relief to the patients, there is need for new formulations able to retain on the oral mucosa. The prolonged moisture protection could be achieved by combining mucoadhesive materials, such as polymers containing hydrogen bonding groups, with vesicles capable of releasing hydration medium from the inner compartment. In this study three different types of liposomes (positively, negatively and neutrally charged) were coated with five different types of polymers: low-methoxylated pectin (LM-pectin), high-methoxylated pectin (HM-pectin), alginate, chitosan and hydrophobically modified ethyl hydroxyethyl cellulose (HM-EHEC). The particle size and the zeta potential of the obtained carriers were tested by measuring dynamic light scattering (DLS) and electrophoretic mobility. Later on, selected positively charged liposomes were deposited on a negatively charged mica surface and depicted by atomic force microscopy (AFM). The water sorption properties of polymers, uncoated liposomes and polymer-coated liposomes were studied by the means of dynamic vapor sorption (DVS). The experiments were performed within the relative humidity range RH=95-0-95%, at 35°C. It was found that coating the liposomes with polymers significantly increased the water sorption capacity of the formulations, making them an attractive choice for hydration of the oral mucosa. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2017-01-28

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

  14. Development of Liposomal Formulation for Delivering Anticancer Drug to Breast Cancer Stem-Cell-Like Cells and its Pharmacokinetics in an Animal Model.

    Science.gov (United States)

    Ahmad, Ajaz; Mondal, Sujan Kumar; Mukhopadhyay, Debabrata; Banerjee, Rajkumar; Alkharfy, Khalid M

    2016-03-07

    The objective of the present study is to develop a liposomal formulation for delivering anticancer drug to breast cancer stem-cell-like cells, ANV-1, and evaluate its pharmacokinetics in an animal model. The anticancer drug ESC8 was used in dexamethasone (Dex)-associated liposome (DX) to form ESC8-entrapped liposome named DXE. ANV-1 cells showed high-level expression of NRP-1. To enhance tumor regression, we additionally adapted to codeliver the NRP-1 shRNA-encoded plasmid using the established DXE liposome. In vivo efficacy of DXE-NRP-1 was carried out in mice bearing ANV-1 cells as xenograft tumors and the extent of tumor growth inhibition was evaluated by tumor-size measurement. A significant difference in tumor volume started to reveal between DXE-NRP-1 group and DXE-Control group. DXE-NRP-1 group showed ∼4 folds and ∼2.5 folds smaller tumor volume than exhibited by untreated and DXE-Control-treated groups, respectively. DXE disposition was evaluated in Sprague-Dawley rats following an intraperitoneal dose (3.67 mg/kg of ESC8 in DXE). The plasma concentrations of ESC8 in the DXE formulation were measured by liquid chromatography mass spectrometry and pharmacokinetic parameters were determined using a noncompartmental analysis. ESC8 had a half-life of 11.01 ± 0.29 h, clearance of 2.10 ± 3.63 L/kg/h, and volume of distribution of 33.42 ± 0.83 L/kg. This suggests that the DXE liposome formulation could be administered once or twice daily for therapeutic efficacy. In overall, we developed a potent liposomal formulation with favorable pharmacokinetic and tumor regressing profile that could sensitize and kill highly aggressive and drug-resistive cancer stem-cell-like cells.

  15. Association of Liposome-Encapsulated Trivalent Antimonial with Ascorbic Acid: An Effective and Safe Strategy in the Treatment of Experimental Visceral Leishmaniasis

    Science.gov (United States)

    Castro, Renata A. O.; Silva-Barcellos, Neila M.; Licio, Carolina S. A.; Souza, Janine B.; Souza-Testasicca, Míriam C.; Ferreira, Flávia M.; Batista, Mauricio A.; Silveira-Lemos, Denise; Moura, Sandra L.; Frézard, Frédéric; Rezende, Simone A.

    2014-01-01

    Background: Visceral leishmaniasis (VL) is a chronic debilitating disease endemic in tropical and subtropical areas, caused by protozoan parasites of the genus Leishmania. Annually, it is estimated the occurrence of 0.2 to 0.4 million new cases of the disease worldwide. Considering the lack of an effective vaccine the afflicted population must rely on both, an accurate diagnosis and successful treatment to combat the disease. Here we propose to evaluate the efficacy of trivalent antimonial encapsulated in conventional liposomes, in association with ascorbic acid, by monitoring its toxicity and efficacy in BALB/c mice infected with Leishmania infantum. Methodology/Principal Findings: Infected mice were subjected to single-dose treatments consisting in the administration of either free or liposome-encapsulated trivalent antimony (SbIII), in association or not with ascorbic acid. Parasite burden was assessed in the liver, spleen and bone marrow using the serial limiting dilution technique. After treatment, tissue alterations were examined by histopathology of liver, heart and kidney and confirmed by serum levels of classic biomarkers. The phenotypic profile of splenocytes was also investigated by flow cytometry. Treatment with liposome-encapsulated SbIII significantly reduced the parasite burden in the liver, spleen and bone marrow. Co-administration of ascorbic acid, with either free SbIII or its liposomal form, did not interfere with its leishmanicidal activity and promoted reduced toxicity particularly to the kidney and liver tissues. Conclusions/Significance: Among the evaluated posological regimens treatment of L. infantum-infected mice with liposomal SbIII, in association with ascorbic acid, represented the best alternative as judged by its high leishmanicidal activity and absence of detectable toxic effects. Of particular importance, reduction of parasite burden in the bone marrow attested to the ability of SbIII-carrying liposomes to efficiently reach this

  16. Propylene glycol liposomes as a topical delivery system for miconazole nitrate: comparison with conventional liposomes.

    Science.gov (United States)

    Elmoslemany, Riham M; Abdallah, Ossama Y; El-Khordagui, Labiba K; Khalafallah, Nawal M

    2012-06-01

    Propylene glycol (PG)-phospholipid vesicles have been advocated as flexible lipid vesicles for enhanced skin delivery of drugs. To further characterize the performance of these vesicles and to address some relevant pharmaceutical issues, miconazole nitrate(MN)-loaded PG nanoliposomes were prepared and characterized for vesicle size, entrapment efficiency, in vitro release, and vesicle stability. An issue of pharmaceutical importance is the time-dependent, dilution-driven diffusion of propylene glycol out of the vesicles. This was addressed by assessing propylene glycol using gas chromatography in the separated vesicles and monitoring its buildup in the medium after repeated dispersion of separated vesicles in fresh medium. Further, the antifungal activity of liposomal formulations under study was assessed using Candida albicans, and their in vitro skin permeation and retention were studied using human skin. At all instances, blank and drug-loaded conventional liposomes were included for comparison. The results provided evidence of controlled MN delivery, constant percent PG uptake in the vesicles (≈45.5%) in the PG concentration range 2.5 to 10%, improved vesicle stability, and enhanced skin deposition of MN with minimum skin permeation. These are key issues for different formulation and performance aspects of propylene glycol-phospholipid vesicles.

  17. Multivesicular liposomal bupivacaine at the sciatic nerve

    Science.gov (United States)

    McAlvin, J. Brian; Padera, Robert F.; Shankarappa, Sahadev A.; Reznor, Gally; Kwon, Albert H.; Chiang, Homer; Yang, Jason; Kohane, Daniel S.

    2014-01-01

    Clinical translation of sustained release formulations for local anesthetics has been limited by adverse tissue reaction. Exparel™ (DepoFoam bupivacaine) is a new liposomal local anesthetic formulation whose biocompatibility near nerve tissue is not well characterized. Exparel™ injection caused sciatic nerve blockade in rats lasting 240 minutes compared to 120 minutes for 0.5% (w/v) bupivacaine HCl and 210 minutes for 1.31% (w/v) bupivacaine HCl (same bupivacaine content as Exparel™). On histologic sections four days after injection, median inflammation scores in the Exparel™ group (2.5 of 4) were slightly higher than in groups treated with bupivacaine solutions (score 2). Myotoxicity scores in the Exparel™ group (2.5 of 6) were similar to in the 0.5% (w/v) bupivacaine HCl group (3), but significantly less than in the 1.31% (w/v) bupivacaine HCl group (5). After two weeks, inflammation from Exparel™ (score 2 of 6) was greater than from 0.5% (w/v) bupivacaine HCl (1) and similar to that from 1.31% (w/v) bupivacaine HCl (1). Myotoxicity in all three groups was not statistically significantly different. No neurotoxicity was detected in any group. Tissue reaction to Exparel™ was similar to that of 0.5% (w/v) bupivacaine HCl. Surveillance for local tissue injury will be important during future clinical evaluation. PMID:24612918

  18. Spontaneous Thigh Compartment Syndrome

    Directory of Open Access Journals (Sweden)

    Khan, Sameer K

    2011-02-01

    Full Text Available A young man presented with a painful and swollen thigh, without any history of trauma, illness, coagulopathic medication or recent exertional exercise. Preliminary imaging delineated a haematoma in the anterior thigh, without any fractures or muscle trauma. Emergent fasciotomies were performed. No pathology could be identified intra-operatively, or on follow-up imaging. A review of thigh compartment syndromes described in literature is presented in a table. Emergency physicians and traumatologists should be cognisant of spontaneous atraumatic presentations of thigh compartment syndrome, to ensure prompt referral and definitive management of this limb-threatening condition. [West J Emerg Med. 2011;12(1:134-138].

  19. In vitro evolution of α-hemolysin using a liposome display.

    Science.gov (United States)

    Fujii, Satoshi; Matsuura, Tomoaki; Sunami, Takeshi; Kazuta, Yasuaki; Yomo, Tetsuya

    2013-10-15

    In vitro methods have enabled the rapid and efficient evolution of proteins and successful generation of novel and highly functional proteins. However, the available methods consider only globular proteins (e.g., antibodies, enzymes) and not membrane proteins despite the biological and pharmaceutical importance of the latter. In this study, we report the development of a method called liposome display that can evolve the properties of membrane proteins entirely in vitro. This method, which involves in vitro protein synthesis inside liposomes, which are cell-sized phospholipid vesicles, was applied to the pore-forming activity of α-hemolysin, a membrane protein derived from Staphylococcus aureus. The obtained α-hemolysin mutant possessed only two point mutations but exhibited a 30-fold increase in its pore-forming activity compared with the WT. Given the ability to synthesize various membrane proteins and modify protein synthesis and functional screening conditions, this method will allow for the rapid and efficient evolution of a wide range of membrane proteins.

  20. Application of HPLC with ELSD Detection for the Assessment of Azelaic Acid Impurities in Liposomal Formulation

    Directory of Open Access Journals (Sweden)

    Stanislaw Han

    2013-01-01

    Full Text Available In the course of research and development of a new pharmaceutical formulation of azelaic acid in the liposomal form, we developed a rapid and accurate method for the detection of impurities using high-performance liquid chromatography. A chromatographic column from Merck (Purospher Star RP C18, 250–4 mm (5 μm was used in the assay, and the mobile phase gradient consisted of three phases: A—methanol : water (5 : 95 + 1.5% (v/v acetic acid; B—water : methanol (5 : 95 + 1.5% (v/v acetic acid; and C—chloroform. Detection of the impurities and the active substance was performed by an evaporative light-scattering detector. The method was validated for selectivity, system precision, method precision, limit of detection, and response rates. The proposed method can be used to detect impurities in the liposomal formulation of azelaic acid. The method enables separation of azelaic acid from the identified and unidentified impurities and from the excipients used in the drug form.

  1. Application of HPLC with ELSD detection for the assessment of azelaic acid impurities in liposomal formulation.

    Science.gov (United States)

    Han, Stanislaw; Karlowicz-Bodalska, Katarzyna; Szura, Dorota; Ozimek, Lukasz; Musial, Witold

    2013-01-01

    In the course of research and development of a new pharmaceutical formulation of azelaic acid in the liposomal form, we developed a rapid and accurate method for the detection of impurities using high-performance liquid chromatography. A chromatographic column from Merck (Purospher Star RP C18, 250-4 mm (5 μm) was used in the assay, and the mobile phase gradient consisted of three phases: A--methanol : water (5 : 95) + 1.5% (v/v) acetic acid; B--water : methanol (5 : 95) + 1.5% (v/v) acetic acid; and C--chloroform. Detection of the impurities and the active substance was performed by an evaporative light-scattering detector. The method was validated for selectivity, system precision, method precision, limit of detection, and response rates. The proposed method can be used to detect impurities in the liposomal formulation of azelaic acid. The method enables separation of azelaic acid from the identified and unidentified impurities and from the excipients used in the drug form.

  2. Uptake of free, calcium-bound and liposomal encapsulated nitrogen containing bisphosphonates by breast cancer cells.

    Science.gov (United States)

    Zlatev, Hristo P; Auriola, Seppo; Mönkkönen, Jukka; Määttä, Jorma A

    2016-04-30

    We have examined the uptake routes by which breast cancer cells internalize different formulations of nitrogen containing bisphosphonates (N-BPs). Cell viability was assessed with the tetrazolium colorimetric test (MTT assay) after treatment with different N-BP formulations in the presence or absence of inhibitors for different endocytosis mechanisms. Intracellular formation of isopentenyl pyrophosphate (IPP) and triphosphoric acid 1-adenosin-5'-yl ester 3-(3-methylbut-3-enyl) ester (ApppI), were quantified with mass spectrometry (ES-LTQ-MS) as surrogate markers for N-BP efficacy. Direct quantification intracellular [(14)C]-labeled zoledronic acid was done with liquid scintillation counting. The main uptake route for all the different formulations of nitrogen containing bisphosphonates was shown to be dynamin dependent endocytosis, which was significantly enhanced with calcium. This uptake mechanism was mostly caveolin and clathrin independent in MCF7 cells, but more clathrin dependent in T47D cells. Liposome encapsulation of the drug shifted the uptake mechanism to be more dependent on caveolin in both the cell lines. The cytotoxicity of N-BPs and the concentrations of formed intracellular ApppI and IPP were significantly increased by calcium chelation and liposome encapsulation, the latter being the most potent formulation. Nitrogen containing bisphosphonates require active endocytosis for cellular uptake and in the breast cancer cells the mechanism is uniformly dynamin dependent for all the formulations tested. This differs e.g. from the previous observations on macrophages, which mostly utilize macropinocytosis. Liposomal formulation was found to prolong the duration of the drug effect in cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Radiolabeling of liposomes and polymeric micelles with PET-isotopes

    DEFF Research Database (Denmark)

    Jensen, Andreas Tue Ingemann

    This thesis is divided into three separate chapters that can be read independently. Chapter 1 is a general introduction, touching upon liposomes and polymeric micelles and radiolabeling with 18F and 64Cu. Chapter 2 and 3 address two separate research projects, each described below. A complete...... as a revolution in modern therapeutics, especially in chemotherapy. A major reason is the ability of nanoparticles to accumulate in tumor tissue. Liposomes are the classic nanoparticle, consisting of a lipid membrane with an aqueous core. Polymeric micelles are made from amphiphilic detergent‐like copolymers......‐life only allowing up to 8 hours scans. 18F must be covalently attached to components of the liposome. By binding to a lipid, it can be stably lodged in the membrane. A glycerolipid and a cholesteryl ether were synthesized with free primary alcohols and a series of their sulphonates (Ms, Ts, Tf) were...

  4. Lipophilic drug transfer between liposomal and biological membranes

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  5. Spontaneous Tumor Lysis Syndrome

    Directory of Open Access Journals (Sweden)

    Alicia C. Weeks MD

    2015-08-01

    Full Text Available Tumor lysis syndrome (TLS is a known complication of malignancy and its treatment. The incidence varies on malignancy type, but is most common with hematologic neoplasms during cytotoxic treatment. Spontaneous TLS is thought to be rare. This case study is of a 62-year-old female admitted with multisystem organ failure, with subsequent diagnosis of aggressive B cell lymphoma. On admission, laboratory abnormalities included renal failure, elevated uric acid (20.7 mg/dL, and 3+ amorphous urates on urinalysis. Oliguric renal failure persisted despite aggressive hydration and diuretic use, requiring initiation of hemodialysis prior to chemotherapy. Antihyperuricemic therapy and hemodialysis were used to resolve hyperuricemia. However, due to multisystem organ dysfunction syndrome with extremely poor prognosis, the patient ultimately expired in the setting of a terminal ventilator wean. Although our patient did not meet current TLS criteria, she required hemodialysis due to uric acid nephropathy, a complication of TLS. This poses the clinical question of whether adequate diagnostic criteria exist for spontaneous TLS and if the lack of currently accepted guidelines has resulted in the underestimation of its incidence. Allopurinol and rasburicase are commonly used for prevention and treatment of TLS. Although both drugs decrease uric acid levels, allopurinol mechanistically prevents formation of the substrate rasburicase acts to solubilize. These drugs were administered together in our patient, although no established guidelines recommend combined use. This raises the clinical question of whether combined therapy is truly beneficial or, conversely, detrimental to patient outcomes.

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

    Directory of Open Access Journals (Sweden)

    Kneidl B

    2014-09-01

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

  7. PEG minocycline-liposomes ameliorate CNS autoimmune disease.

    Directory of Open Access Journals (Sweden)

    Wei Hu

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

  8. Targeting Epirubicin Plus Quinacrine Liposomes Modified with DSPE-PEG2000-C(RGDfK) Conjugate for Eliminating Invasive Breast Cancer.

    Science.gov (United States)

    Sun, Meng-Ge; Shi, Ji-Feng; Li, Xiu-Ying; Zhao, Yao; Ju, Rui-Jun; Mu, Li-Min; Yan, Yan; Li, Xue-Tao; Zeng, Fan; Lu, Wan-Liang

    2015-08-01

    Recurrence of invasive breast cancer could arise from the residual cancer cells after comprehensive treatment. It is possible that residual invasive cancer cells are capable of forming highly patterned vasculogenic mimicry (VM) channels, leading to relapse and metastasis. In the present study, a new type of targeting epirubicin plus quinacrine liposomes was developed by modifying functional DSPE-PEG2000 with C(RGDfK), a cyclic peptide containing Arg-Gly-Asp. These liposomes could potentially eliminate invasive breast cancer and destroy VM channels. Evaluations were made in human invasive breast cancer cells and their xenografts in nude mice. The results showed that the targeting epirubicin plus quinacrine liposomes could enhance the accumulation and uptake of the drugs in cancer tissues, kill cancer cells directly, activate apoptotic enzymes, destroy the VM channels and downregulate the VM channel-forming marker molecules (EphA2, FAK, PI3K, MMP 9, MMP 14, VE-Cad and HIF-α), thereby exhibiting a strong overall anticancer efficacy. The targeting epirubicin plus quinacrine liposomes provided a promising strategy to treat invasive breast cancer and to prevent the relapse arising from VM channels after chemotherapy.

  9. Mass-action model analysis of the apparent molar volume and heat capacity of pluronics in water and liposome suspensions at 25 °C.

    Science.gov (United States)

    Quirion, François; Meilleur, Luc; Lévesque, Isabelle

    2013-07-09

    Pluronics are block copolymers composed of a central block of polypropylene oxide and two side chains of polyethylene oxide. They are used in water to generate aggregates and gels or added to phospholipid suspensions to prepare microparticles for drug delivery applications. The structure of these systems has been widely investigated. However, little is known about the mechanisms leading to these structures. This investigation compares the apparent molar volumes and heat capacities of Pluronics F38, F108, F127, P85, P104, and P103 at 25 °C in water and in the presence of lecithin liposomes. The changes in molar volumes, heat capacities, and enthalpies generated by a mass-action model are in good agreement with the loss of hydrophobic hydration of the polypropylene oxide central block of the Pluronics. However, the molecularity of the endothermic transitions is much smaller than the aggregation numbers reported in the literature for the same systems. It is suggested that Pluronics go through dehydration of their central block to form unimolecular or small entities having a hydrophobic polypropylene oxide core. In water, these entities would assemble athermally to form larger aggregates. In the presence of liposomes, they would be transferred into the hydrophobic lecithin bilayers of the liposomes. Light transmission experiments suggest that the liposome suspensions are significantly altered only when the added Pluronics are in the dehydrated state.

  10. Individual differences in spontaneous analogical transfer.

    Science.gov (United States)

    Kubricht, James R; Lu, Hongjing; Holyoak, Keith J

    2017-05-01

    Research on analogical problem solving has shown that people often fail to spontaneously notice the relevance of a semantically remote source analog when solving a target problem, although they are able to form mappings and derive inferences when given a hint to recall the source. Relatively little work has investigated possible individual differences that predict spontaneous transfer, or how such differences may interact with interventions that facilitate transfer. In this study, fluid intelligence was measured for participants in an analogical problem-solving task, using an abridged version of the Raven's Progressive Matrices (RPM) test. In two experiments, we systematically compared the effect of augmenting verbal descriptions of the source with animations or static diagrams. Solution rates to Duncker's radiation problem were measured across varying source presentation conditions, and participants' understanding of the relevant source material was assessed. The pattern of transfer was best fit by a moderated mediation model: the positive impact of fluid intelligence on spontaneous transfer was mediated by its influence on source comprehension; however, this path was in turn modulated by provision of a supplemental animation via its influence on comprehension of the source. Animated source depictions were most beneficial in facilitating spontaneous transfer for those participants with low scores on the fluid intelligence measure.

  11. Time-controlled phagocytosis of asymmetric liposomes: Application to phosphatidylserine immunoliposomes binding HIV-1 virus-like particles.

    Science.gov (United States)

    Petazzi, Roberto Arturo; Gramatica, Andrea; Herrmann, Andreas; Chiantia, Salvatore

    2015-11-01

    Macrophage immune functions such as antibody-mediated phagocytosis are strongly impaired in individuals affected by HIV-1. Nevertheless, infected macrophages are still able to phagocytose apoptotic cells. For this reason, we recently developed antibody-decorated phosphatidylserine (PS)-containing liposomes that bind HIV-1 virus-like particles and, by mimicking apoptotic cells, are efficiently internalized by macrophages. In the context of an in vivo application, it would be extremely important to initially protect immunoliposomes from macrophages, in order to provide enough time to redistribute through the body and achieve maximum virus binding. To this end, we have designed asymmetric immunoliposomes in which the PS is initially confined to the inner leaflet and thus cannot be recognized by macrophages. Spontaneous PS flip-flop to the outer surface leads to a time-delay in internalization by macrophages in vitro. Such a delay can be fine-tuned by altering the molecular composition of the immunoliposomes. In the fight against HIV-1, macrophage plays an important role. Ironically, the phagocytic functions of these cells are often impaired by HIV-1. In this interesting article, the authors described the development of asymmetric liposomes, which would bind HIV-1 with prolonged systemic circulation, such that the clearance of virus by macrophages is enhanced. This system represents a promising effective approach to utilize the phagocytic capability of macrophages. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Interaction of sodium diclofenac with freeze-dried soya phosphatidylcholine and unilamellar liposomes Interação do diclofenaco com fosfatidilcolina de soja e lipossomas unilamelares liofilizados

    Directory of Open Access Journals (Sweden)

    Luciana Biagini Lopes

    2006-12-01

    Full Text Available Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study, we have analyzed the interaction the sodium diclofenac (SD with soya phosphaditylcholine (PC and soya phosphatidylcholine from lyophilized small unilamellar liposomes (SUV. The changes in the properties of the co-lyophilized drug/PC from SUV liposomes, lyophilized PC from SUV liposomes, and lyophilized soya phosphatidylcholine, were studied by Differential Scanning Calorimetry (DSC. The DSC data showed that the previous organization of phospholipids molecules to form liposome affects intensely the thermal behavior of PC when compared to non-lipossomal PC. SD modified the thermal properties of PC from liposomes. It was verified that SD affects intensely the located group peaks in the regions of 120-140 ºC and in the higher temperature region of 240-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-liposomal PC and that these modifications can be easily monitored by DSC analysis.Fosfolipídios são freqüentemente usados como compostos anfifílicos estruturais em formulações de lipossomas. Neste estudo foi analisada a interação do diclofenaco sódico (SD com a fosfatidilcolina de soja liofilizada e a fosfatidilcolina de soja (PC obtida de lipossomas unilamelares pequenos liofilizados (SUV. As modificações nas propriedades da mistura fármaco/PC co-liofilizados a partir de SUV pré-formados, lipossomas de PC vazios e PC liofilizada foram estudadas por Calorimetria Diferencial de Varredura (DSC. Os resultados de DSC mostraram que a organização prévia das moléculas PC para formar lipossomas interfere significativamente no perfil de DSC da PC, quando comparada ao perfil de DSC da PC não-lipossômica. Verificou-se que o SD afeta intensamente o grupo de picos situados nas regiões de 120-140ºC e na região de mais alta temperatura (240-260ºC. Os resultados

  13. Ultra magnetic liposomes for MR imaging, targeting, and hyperthermia.

    Science.gov (United States)

    Béalle, Gaëlle; Di Corato, Riccardo; Kolosnjaj-Tabi, Jelena; Dupuis, Vincent; Clément, Olivier; Gazeau, Florence; Wilhelm, Claire; Ménager, Christine

    2012-08-14

    Magnetic liposomes offer opportunities as theranostic systems. The prerequisite for efficient imaging, tissue targeting or hyperthermia is high magnetic load of these vesicles. Here we describe the preparation of Ultra Magnetic Liposomes (UMLs), which may encapsulate iron oxide nanoparticles in a volume fraction of up to 30%. This remarkable magnetic charge provides UMLs with high magnetic mobilities, MRI relaxivities, and heating capacities for magnetic hyperthermia. Moreover, these UMLs are rapidly and efficiently internalized by cultured tumor cells and, when they are administered to mice, they can be vectorized to tumors by an external magnet.

  14. Efficient liposome fusion mediated by lipid-nucleic acid conjugates

    DEFF Research Database (Denmark)

    Ries, O; Löffler, P M G; Rabe, A

    2017-01-01

    The fusion of biomembranes with release of encapsulated content in a controlled way is crucial for cell signaling, endo- and exocytosis and intracellular trafficking. Programmable fusion of liposomes and an efficient mixing of their contents have the potential to enable the study of chemical...... and enzymatic processes in a confined environment and under crowded conditions outside biological systems. We report on DNA-controlled fusion of lipid bilayer membranes using lipid-nucleic acid conjugates (LiNAs) to mediate lipid and content mixing of liposomes. Screening of different membrane anchor and linker...

  15. Preparation and Use of Liposomes in Immunological Studies

    Science.gov (United States)

    1993-01-01

    single or a few intravenous (i.v.), intramuscular (i.m.) or subcutaneous (s.c.) injections. An advantage to immunization with lipo- somes is that the...greater than one year.’’ Liposomes are prepared as described in Section V.A. Just prior to im- munization, the liposomes are mixed with alum ( aluminum ...approximately 10 mg of aluminum per ml. This stock suspension settles out on storage and must be resuspended by mixing on a rotary shaker for 5 h. The desired

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Eiji Yuba

    2018-01-01

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

  18. Liposome-encapsulated ursolic acid increases ceramides and collagen in human skin cells.

    Science.gov (United States)

    Both, Dawn M; Goodtzova, Karina; Yarosh, Daniel B; Brown, David A

    2002-01-01

    Skin wrinkling and xerosis associated with aging result from decreases in dermal collagen and stratum corneum ceramide content. This study demonstrated that ursolic acid incorporated into liposomes (URA liposomes) increases both the ceramide content of cultured normal human epidermal keratinocytes (NHEK), and the collagen content of cultured normal human dermal fibroblasts. In addition, URA liposomes increased the ceramide content of the skin of human subjects, with increases in hydroxy ceramides occurring after only 3 days of treatment. Both URA liposomes and retinoic acid decreased markers of keratinocyte differentiation (keratin 1, keratin 10 and involucrin) in cultured NHEK. Thus, URA liposomes have effects on keratinocyte differentiation and dermal fibroblast collagen synthesis similar to those of retinoids. However, this study showed that URA liposomes increase ceramides in NHEK, in contrast to the decreases previously shown to be caused by retinoids. URA liposomes have the potential to be used alone or in combination with other agents to restore or maintain skin ceramide and collagen content.

  19. Spontaneous Intracranial Hypotension

    International Nuclear Information System (INIS)

    Joash, Dr.

    2015-01-01

    Epidemiology is not only rare but an important cause of new daily persistent headaches among young & middle age individuals. The Etiology & Pathogenesis is generally caused by spinal CSF leak. Precise cause remains largely unknown, underlying structural weakness of spinal meninges is suspected. There are several MR Signs of Intracranial Hypotension that include:- diffuse pachymeningeal (dural) enhancement; bilateral subdural, effusion/hematomas; Downward displacement of brain; enlargement of pituitary gland; Engorgement of dural venous sinuses; prominence of spinal epidural venous plexus and Venous sinus thrombosis & isolated cortical vein thrombosis. The sum of volumes of intracranial blood, CSF & cerebral tissue must remain constant in an intact cranium. Treatment in Many cases can be resolved spontaneously or by use Conservative approach that include bed rest, oral hydration, caffeine intake and use of abdominal binder. Imaging Modalities for Detection of CSF leakage include CT myelography, Radioisotope cisternography, MR myelography, MR imaging and Intrathecal Gd-enhanced MR

  20. Spontaneous wave packet reduction

    International Nuclear Information System (INIS)

    Ghirardi, G.C.

    1994-06-01

    There are taken into account the main conceptual difficulties met by standard quantum mechanics in dealing with physical processes involving macroscopic system. It is stressed how J.A.Wheeler's remarks and lucid analysis have been relevant to pinpoint and to bring to its extreme consequences the puzzling aspects of quantum phenomena. It is shown how the recently proposed models of spontaneous dynamical reduction represent a consistent way to overcome the conceptual difficulties of the standard theory. Obviously, many nontrivial problems remain open, the first and more relevant one being that of generalizing the model theories considered to the relativistic case. This is the challenge of the dynamical reduction program. 43 refs, 2 figs

  1. Evaluation of antinociceptive activity of nanoliposome-encapsulated and free-form diclofenac in rats and mice

    Directory of Open Access Journals (Sweden)

    Goh JZ

    2014-12-01

    Full Text Available Jun Zheng Goh,1 Sook Nai Tang,1 Hoe Siong Chiong,1,2 Yoke Keong Yong,3 Ahmad Zuraini,1 Muhammad Nazrul Hakim1,4 1Department of Biomedical Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2InQpharm Group, Kuala Lumpur, Malaysia; 3Department of Human Anatomy, 4Halal Product Research Institute, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Abstract: Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID that exhibits anti-inflammatory, antinociceptive, and antipyretic activities. Liposomes have been shown to improve the therapeutic efficacy of encapsulated drugs. The present study was conducted to compare the antinociceptive properties between liposome-encapsulated and free-form diclofenac in vivo via different nociceptive assay models. Liposome-encapsulated diclofenac was prepared using the commercialized proliposome method. Antinociceptive effects of liposome-encapsulated and free-form diclofenac were evaluated using formalin test, acetic acid-induced abdominal writhing test, Randall–Selitto paw pressure test, and plantar test. The results of the writhing test showed a significant reduction of abdominal constriction in all treatment groups in a dose-dependent manner. The 20 mg/kg liposome-encapsulated diclofenac demonstrated the highest antinociceptive effect at 78.97% compared with 55.89% in the free-form group at equivalent dosage. Both liposome-encapsulated and free-form diclofenac produced significant results in the late phase of formalin assay at a dose of 20 mg/kg, with antinociception percentages of 78.84% and 60.71%, respectively. Significant results of antinociception were also observed in both hyperalgesia assays. For Randall–Sellito assay, the highest antinociception effect of 71.38% was achieved with 20 mg/kg liposome-encapsulated diclofenac, while the lowest antinociceptive effect of 17.32% was recorded with 0 mg/kg liposome formulation, whereas in the plantar test, the highest antinociceptive effect

  2. Evaluation of the Antimicrobial and Antioxidant Activities of Origanum dictamnus Extracts before and after Encapsulation in Liposomes

    Directory of Open Access Journals (Sweden)

    John Tsaknis

    2007-05-01

    Full Text Available The antioxidant and antimicrobial activity of methanol or dichloromethane extracts of O. dictamnus, produced from wild and organic cultivated specimens, were determined. The Rancimat and malondialdehyde (MDA by HPLC methods were used to measure the antioxidant action, in comparison with that of the common commercial antioxidants butylated hydroxytoluene (BHT and α-tocopherol. The extracts that presented high antioxidant activity were encapsulated in liposomes and their antioxidant action was again estimated using differential scanning calorimetry (DSC. Thermaloxidative decomposition of the samples (pure liposomes and encapsulated extracts and the modification of the main transition temperature for the lipid mixture and the splitting of the calorimetric peak in the presence of the antioxidants were also studied by the DSC method. All extracts showed antioxidant and antimicrobial activities. Their action proved superior to α-tocopherol. The methanol extract of organic cultivated O. dictamnus (240 ppm showed higher activity than butylated hydroxytoluene. After encapsulation in liposomes the antioxidant as well as antimicrobial activities proved to be higher than those of the same extracts in pure form.

  3. Conversion of liposomal 4-androsten-3,17-dione by A. simplex immobilized cells in calcium pectate.

    Science.gov (United States)

    Llanes, Nury; Pendás, Jehzabel; Falero, Alina; Pérez, Celso; Hung, Blanca R; Moreira, Tomás

    2002-01-01

    Arthrobacter simplex ATCC 6946 free and immobilized cells were assayed for their ability to convert 4-androsten-3,17-dione (AD) to 1,4-androstadien-3,17-dione (ADD) in aqueous and liposomal media. Bioconversions were carried out in a 100 ml flask containing 25 ml of AD liposomal or aqueous medium for 3h, and AD concentrations ranging from 0.3 to 1.0 mM were tested. AD/ADD ratios in samples were determined by HPLC. Biotransformation of substrate entrapped in multilamellar vesicles (MLV) was demonstrated to be better than the corresponding free form. In the former case, 2h were necessary to completely bioconvert 1 mM AD. By contrast, 3h were needed to reach 50% bioconversion in (4%) ethanol medium containing 0.63 mM AD. The liposomal medium allows us to perform steroid conversions at high concentrations of AD, reusing immobilized cells in suitable conditions which are non-toxic for microorganisms.

  4. Visualization of liposomes by magnetic resonance imaging: an opportunity to improve antitumoral liposome therapies

    International Nuclear Information System (INIS)

    Martinez Bedoya, Darel

    2012-01-01

    Controlled release of drugs at the tumor site and the development of non-invasive monitoring techniques are two of the main challenges currently facing antitumoral therapies. The paper analyzes some of the potential uses of liposomes as vehicles for the transport of drugs to the tumors, particularly directionalized variants to tumor antigens through antibody coupling (immunoliposomes). These vesicles may also be used in combination with magnetic resonance, one of the most widely used imaging techniques, and one exhibiting great visualization potential at molecular level. Joint use of these two techniques makes it possible to control the amount of drug administered, as well as predict the efficacy of the treatment and monitor its progress

  5. [Atypical etiology of rhinorrhea: spontaneous bilateral temporal encephalocele].

    Science.gov (United States)

    Lorente Muñoz, Asís; Lisbona Alquézar, María Pilar; González Martínez, Luis; Sevil Navarro, Jorge; Llorente Arenas, Eva María

    2012-01-01

    Spontaneous herniation of brain parenchyma through a dural and osseous defect in the temporal bone is a rare entity and a bilateral form is even more infrequent. It usually presents as an intermittent but persistent otorrhea. Manifestation as nose cerebrospinal fluid (CSF) leak is very uncommon. Our objective is presenting this unusual case report of a spontaneous bilateral encephalocele with a bilateral tegmen tympani defect. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  6. Screening for spontaneous preterm birth

    NARCIS (Netherlands)

    van Os, M.A.; van Dam, A.J.E.M.

    2015-01-01

    Preterm birth is the most important cause of perinatal morbidity and mortality worldwide. In this thesis studies on spontaneous preterm birth are presented. The main objective was to investigate the predictive capacity of mid-trimester cervical length measurement for spontaneous preterm birth in a

  7. Liposomal Formulation of Turmerone-Rich Hexane Fractions from Curcuma longa Enhances Their Antileishmanial Activity

    Directory of Open Access Journals (Sweden)

    Ana Claudia F. Amaral

    2014-01-01

    Full Text Available Promastigote forms of Leishmania amazonensis were treated with different concentrations of two fractions of Curcuma longa cortex rich in turmerones and their respective liposomal formulations in order to evaluate growth inhibition and the minimal inhibitory concentration (MIC. In addition, cellular alterations of treated promastigotes were investigated under transmission and scanning electron microscopies. LipoRHIC and LipoRHIWC presented lower MIC, 5.5 and 12.5 μg/mL, when compared to nonencapsulated fractions (125 and 250 μg/mL, respectively, and to ar-turmerone (50 μg/mL. Parasite growth inhibition was demonstrated to be dose-dependent. Important morphological changes as rounded body and presence of several roles on plasmatic membrane could be seen on L. amazonensis promastigotes after treatment with subinhibitory concentration (2.75 μg/mL of the most active LipoRHIC. In that sense, the hexane fraction from the turmeric cortex of Curcuma longa incorporated in liposomal formulation (LipoRHIC could represent good strategy for the development of new antileishmanial agent.

  8. In vivo treatment of Propionibacterium acnes infection with liposomal lauric acids.

    Science.gov (United States)

    Pornpattananangkul, Dissaya; Fu, Victoria; Thamphiwatana, Soracha; Zhang, Li; Chen, Michael; Vecchio, James; Gao, Weiwei; Huang, Chun-Ming; Zhang, Liangfang

    2013-10-01

    Propionibacterium acnes (P. acnes) is a Gram-positive bacterium strongly associated with acne infection. While many antimicrobial agents have been used in clinic to treat acne infection by targeting P. acnes, these existing anti-acne agents usually produce considerable side effects. Herein, the development and evaluation of liposomal lauric acids (LipoLA) is reported as a new, effective and safe therapeutic agent for the treatment of acne infection. By incorporating lauric acids into the lipid bilayer of liposomes, it is observed that the resulting LipoLA readily fuse with bacterial membranes, causing effective killing of P. acnes by disrupting bacterial membrane structures. Using a mouse ear model, we demonstrated that the bactericidal property of LipoLA against P. acne is well preserved at physiological conditions. Topically applying LipoLA in a gel form onto the infectious sites leads to eradication of P. acnes bacteria in vivo. Further skin toxicity studies show that LipoLA does not induce acute toxicity to normal mouse skin, while benzoyl peroxide and salicylic acid, the two most popular over-the-counter acne medications, generate moderate to severe skin irritation within 24 h. These results suggest that LipoLA hold a high therapeutic potential for the treatment of acne infection and other P. acnes related diseases. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Analysis of the Diffusion Process by pH Indicator in Microfluidic Chips for Liposome Production

    Directory of Open Access Journals (Sweden)

    Elisabetta Bottaro

    2017-07-01

    Full Text Available In recent years, the development of nano- and micro-particles has attracted considerable interest from researchers and enterprises, because of the potential utility of such particles as drug delivery vehicles. Amongst the different techniques employed for the production of nanoparticles, microfluidic-based methods have proven to be the most effective for controlling particle size and dispersity, and for achieving high encapsulation efficiency of bioactive compounds. In this study, we specifically focus on the production of liposomes, spherical vesicles formed by a lipid bilayer encapsulating an aqueous core. The formation of liposomes in microfluidic devices is often governed by diffusive mass transfer of chemical species at the liquid interface between a solvent (i.e., alcohol and a non-solvent (i.e., water. In this work, we developed a new approach for the analysis of mixing processes within microfluidic devices. The method relies on the use of a pH indicator, and we demonstrate its utility by characterizing the transfer of ethanol and water within two different microfluidic architectures. Our approach represents an effective route to experimentally characterize diffusion and advection processes governing the formation of vesicular/micellar systems in microfluidics, and can also be employed to validate the results of numerical modelling.

  10. Liposomal Formulation of Turmerone-Rich Hexane Fractions from Curcuma longa Enhances Their Antileishmanial Activity

    Science.gov (United States)

    Amaral, Ana Claudia F.; Gomes, Luciana A.; Silva, Jefferson Rocha de A.; Ferreira, José Luiz P.; Ramos, Aline de S.; Rosa, Maria do Socorro S.; Vermelho, Alane B.; Rodrigues, Igor A.

    2014-01-01

    Promastigote forms of Leishmania amazonensis were treated with different concentrations of two fractions of Curcuma longa cortex rich in turmerones and their respective liposomal formulations in order to evaluate growth inhibition and the minimal inhibitory concentration (MIC). In addition, cellular alterations of treated promastigotes were investigated under transmission and scanning electron microscopies. LipoRHIC and LipoRHIWC presented lower MIC, 5.5 and 12.5 μg/mL, when compared to nonencapsulated fractions (125 and 250 μg/mL), respectively, and to ar-turmerone (50 μg/mL). Parasite growth inhibition was demonstrated to be dose-dependent. Important morphological changes as rounded body and presence of several roles on plasmatic membrane could be seen on L. amazonensis promastigotes after treatment with subinhibitory concentration (2.75 μg/mL) of the most active LipoRHIC. In that sense, the hexane fraction from the turmeric cortex of Curcuma longa incorporated in liposomal formulation (LipoRHIC) could represent good strategy for the development of new antileishmanial agent. PMID:25045693

  11. Liposomal photosensitizers: potential platforms for anticancer photodynamic therapy

    Directory of Open Access Journals (Sweden)

    L.A. Muehlmann

    2011-08-01

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

  12. 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

  13. 64Cu loaded liposomes as positron emission tomography imaging agents

    DEFF Research Database (Denmark)

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

    2011-01-01

    We have developed a highly efficient method for utilizing liposomes as imaging agents for positron emission tomography (PET) giving high resolution images and allowing direct quantification of tissue distribution and blood clearance. Our approach is based on remote loading of a copper...

  14. Damaged hair retrieval with ceramide-rich liposomes.

    Science.gov (United States)

    Méndez, Sandra; Manich, Albert M; Martí, Meritxell; Parra, José L; Coderch, Luisa

    2011-01-01

    Lipids from human hair consist mainly of cholesterol esters, free fatty acids, cholesterol, ceramides, and cholesterol sulfate. They are structured as lipid bilayers in the cell membrane complex (CMC) and make a large contribution to diffusion, cell cohesion, and mechanical strength. The loss of these lipids could impair the integrity of the hair, leading to deterioration in its tensile properties. Internal wool lipids (IWL) resemble those of the membranes of other keratinic tissues such as human hair or stratum corneum. The application of IWL structured as liposomes on pretreated hair samples has been demonstrated to restore the natural properties of the fibers. This study seeks to apply IWL liposomes to untreated hair fibers and to hair fibers subjected to chemical treatment. Differences in the lipidic composition of all chemically treated hairs were found with respect to the untreated ones. Lipid recovery of damaged hair due to the application of IWL liposomes was corroborated by lipid analysis of the hair. A high resistance to break of hair samples post-treated with IWL liposomes was observed. An increase in hydrogen bonds and electrostatic forces and an improvement in the cohesion between matrix and filaments were detected, probably because of some lipid recovery.

  15. Avanafil Liposomes as Transdermal Drug Delivery for Erectile ...

    African Journals Online (AJOL)

    Conclusion: The developed avanafil liposomes represent a promising transdermal drug delivery system for the treatment of erectile dysfunction. ... skin, in recent years, transdermal drug delivery has been used to overcome the problems ... Drugs Technology Co., Ltd. [Hangzhou, China]. The egg phosphatidylcholine (PC), ...

  16. Optical characterization of individual liposome-loaded microbubbles

    NARCIS (Netherlands)

    Faez, T.; Skachkov, I.; Gelderblom, E.C.; Geers, B.; Lentacker, I.; van der Steen, A.F.W.; Versluis, Michel; de Jong, N.

    2012-01-01

    Newly developed liposome-loaded (LPS) microbubbles are characterized by comparing their oscillating response with standard phospholipid-coated (bare) microbubbles using the ultra-high speed imaging (Brandaris 128) camera. A study of the shell properties indicate nearly the same shell elasticity and

  17. A new method for liposome preparation using a membrane contactor.

    Science.gov (United States)

    Jaafar-Maalej, Chiraz; Charcosset, Catherine; Fessi, Hatem

    2011-09-01

    In this article, we present a novel, scalable liposomal preparation technique suitable for the entrapment of pharmaceutical agents into liposomes. This new method is based on the ethanol-injection technique and uses a membrane contactor module, specifically designed for colloidal system preparation. In order to investigate the process, the influence of key parameters on liposome characteristics was studied. It has been established that vesicle-size distribution decreased with a decrease of the organic-phase pressure, an increase of the aqueous-phase flow rate, and a decrease of the phospholipid concentration. Additionally, special attention was paid on reproducibility and long-term stability of lipid vesicles, confirming the robustness of the membrane contactor-based technique. On the other hand, drug-loaded liposomes were prepared and filled with two hydrophobic drug models. High entrapment-efficiency values were successfully achieved for indomethacin (63%) and beclomethasone dipropionate (98%). Transmission electron microscopy images revealed nanometric quasispherical-shaped multilamellar vesicles (size ranging from 50 to 160 nm).

  18. Soft Interaction in Liposome Nanocarriers for Therapeutic Drug Delivery

    Directory of Open Access Journals (Sweden)

    Domenico Lombardo

    2016-06-01

    Full Text Available The development of smart nanocarriers for the delivery of therapeutic drugs has experienced considerable expansion in recent decades, with the development of new medicines devoted to cancer treatment. In this respect a wide range of strategies can be developed by employing liposome nanocarriers with desired physico-chemical properties that, by exploiting a combination of a number of suitable soft interactions, can facilitate the transit through the biological barriers from the point of administration up to the site of drug action. As a result, the materials engineer has generated through the bottom up approach a variety of supramolecular nanocarriers for the encapsulation and controlled delivery of therapeutics which have revealed beneficial developments for stabilizing drug compounds, overcoming impediments to cellular and tissue uptake, and improving biodistribution of therapeutic compounds to target sites. Herein we present recent advances in liposome drug delivery by analyzing the main structural features of liposome nanocarriers which strongly influence their interaction in solution. More specifically, we will focus on the analysis of the relevant soft interactions involved in drug delivery processes which are responsible of main behaviour of soft nanocarriers in complex physiological fluids. Investigation of the interaction between liposomes at the molecular level can be considered an important platform for the modeling of the molecular recognition processes occurring between cells. Some relevant strategies to overcome the biological barriers during the drug delivery of the nanocarriers are presented which outline the main structure-properties relationships as well as their advantages (and drawbacks in therapeutic and biomedical applications.

  19. Formulation of a New Generation of Liposomes from Bacterial and ...

    African Journals Online (AJOL)

    http://dx.doi.org/10.4314/tjpr.v15i2.1. Original Research Article. Formulation of a New Generation of Liposomes from ... extracted from Escherichia coli (E. coli) cultures, and archaeosomes made with lipids derived from .... Krishnamachari Y, Geary SM, Lemke CD, Salem AK. Nanoparticle delivery systems in cancer vaccines.

  20. 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...

  1. Receptor versus non-receptor mediated clearance of liposomes

    NARCIS (Netherlands)

    Scherphof, GL; Kamps, JAAM

    1998-01-01

    Numerous studies have appeared over the years dealing with liposome-cell interaction mechanisms, most of them performed under in vitro conditions with isolated cell populations or cell lines. It is remarkable that, nonetheless, there hardly seem to exist established and generally accepted views on

  2. Synthesis of liposomes using α-phosphotidycholine and metabolites ...

    African Journals Online (AJOL)

    Plant saponins exhibit numerous pharmacological characteristics desirable for long term hyperlipidemic therapy through their cholesterol binding capacity due to the formation of liposomes/phytosomes which ultimately decreases the gastrointestinal absorption of cholesterol. This may result in the reduction of the blood ...

  3. Targeted liposomes for cytosolic drug delivery to tumor cells

    NARCIS (Netherlands)

    Mastrobattista, E.

    2001-01-01

    In this thesis, a Trojan horse strategy with antibody-targeted liposomes has been followed to obtain cytosolic delivery of biotherapeutics to tumor cells in vitro. This strategy involves targeting of immunoliposomes to specific receptors on tumor cells that result in receptor-mediated uptake of the

  4. Liposome encapsulated luteolin showed enhanced antitumor efficacy to colorectal carcinoma

    Science.gov (United States)

    Wu, Guixia; Li, Jing; Yue, Jinqiao; Zhang, Shuying; Yunusi, Kurexi

    2018-01-01

    Luteolin is a falconoid compound that is present in various types of plants and possesses remarkable potential as a chemopreventive agent. However, the poor aqueous solubility of luteolin limits its clinical application. In the present study, an approach towards chemoprevention was explored using liposomes to deliver luteolin, and the antitumor efficacy was investigated in colorectal carcinoma. The present findings demonstrated that luteolin was efficiently encapsulated into liposomes with an encapsulation efficiency as high as 90%. The particle size of the liposomal luteolin (Lipo-Lut) and ζ-potential were optimized. In vitro studies demonstrated that, Lipo-Lut had a significant inhibitory effect on the growth on the CT26 colorectal carcinoma cell line compared with free luteolin (Free-Lut). The in vivo study indicated that Lipo-Lut could achieve superior antitumor effects against CT26 tumor compared with luteolin alone. The present results suggested that liposome delivery of luteolin improved solubility, bioavailability and may have potential applications in chemoprevention in clinical settings. PMID:29207088

  5. Biomolecular Interactions of Tannin Isolated from Oenothera gigas with Liposomes.

    Science.gov (United States)

    Sekowski, Szymon; Ionov, Maksim; Dubis, Alina; Mavlyanov, Saidmukhtar; Bryszewska, Maria; Zamaraeva, Maria

    2016-04-01

    We have examined the interaction between hydrolysable tannin 1-O-galloyl-4,6-hexahydroxydiphenoyl-β-D-glucose (OGβDG) with neutral liposomes as a model of cell membranes composed of three lipids: lecithin, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) at different mass ratios. OGβDG in the concentration range 0.5-15 µg/ml (0.4-12 µM) strongly interacts with liposomal membranes by changing their structure, surface charge and fluidity. Used OGβDG molecules decrease and increase the rigidity of hydrophilic surface and hydrophobic parts of liposomes, respectively. At higher concentrations of tannin (>15 µM), liposomes are aggregated. Fourier Transform Infra-Red (FTIR) analysis showed that mainly -OH groups from OGβDG and also PO(2-) groups from phospholipids are responsible for the interaction. Obtained data indicate the importance of membrane lipid composition in interactions between tannins and cells.

  6. Drug delivery by phospholipase A(2) degradable liposomes

    DEFF Research Database (Denmark)

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

    2001-01-01

    The effect of poly(ethylene glycol)-phospholipid (PE-PEG) lipopolymers on phospholipase A(2) (PLA(2)) hydrolysis of liposomes composed of stearoyl-oleoylphosphatidylcholine (SOPC) was investigated. The PLA(2) lag-time, which is inversely related to the enzymatic activity, was determined by fluore...

  7. Distribution of local anesthetics between aqueous and liposome phases

    Czech Academy of Sciences Publication Activity Database

    Ruokonen, S. K.; Duša, Filip; Rantamäki, A. H.; Robciuc, A.; Holma, P.; Holopainen, J. M.; Abdel-Rehim, M.; Wiedmer, S. K.

    2017-01-01

    Roč. 1479, JAN (2017), s. 194-203 ISSN 0021-9673 Institutional support: RVO:68081715 Keywords : liposome electrokinetic chromatography * distribution constants * EOF markers Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 3.981, year: 2016

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

    DEFF Research Database (Denmark)

    Hamborg, Mette; Jorgensen, Lene; Bojsen, Anders Riber

    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...

  9. Thrombin-Inhibiting Anticoagulant Liposomes: Development and Characterization.

    Science.gov (United States)

    Endreas, Wegderes; Brüßler, Jana; Vornicescu, Doru; Keusgen, Michael; Bakowsky, Udo; Steinmetzer, Torsten

    2016-02-04

    Many peptides and peptidomimetic drugs suffer from rapid clearance in vivo; this can be reduced by increasing their size through oligomerization or covalent conjugation with polymers. As proof of principle, an alternative strategy for drug oligomerization is described, in which peptidomimetic thrombin inhibitors are incorporated into the liposome surface. For this purpose, the inhibitor moieties were covalently coupled to a palmitic acid residue through a short bifunctionalized ethylene glycol spacer. These molecules were directly added to the lipid mixture used for liposome preparation. The obtained liposomes possess strong thrombin inhibitory potency in enzyme kinetic measurements and anticoagulant activity in plasma. Their strong potency and positive ζ potential indicate that large amounts of the benzamidine-derived inhibitors are located on the surface of the liposomes. This concept should be applicable to other drug molecules that suffer from rapid elimination and allow covalent modification with a suitable fatty acid residue. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Effect of Cytotoxicity of Pegylated Liposomal Recombinant Human ...

    African Journals Online (AJOL)

    Purpose: To evaluate the cytotoxic effect of pegylated liposomal Recombinant Human Erythropoietin- alfa (rHuEPO) nanoparticles synthesized by reverse phase evaporation technique on SH-SY5Y cell line. Methods: To prepare the nanoparticles of the drug, rHuEPO, PEG3000, cholesterol and phosphatidylcholine were ...

  11. Activity-Based Protein Profiling of Rhomboid Proteases in Liposomes

    Czech Academy of Sciences Publication Activity Database

    Wolf, E. V.; Seybold, M.; Hadravová, Romana; Stříšovský, Kvido; Verhelst, S. H. L.

    2015-01-01

    Roč. 16, č. 11 (2015), s. 1616-1621 ISSN 1439-4227 R&D Projects: GA MŠk(CZ) LK11206; GA MŠk LO1302 Institutional support: RVO:61388963 Keywords : activity-based protein profiling * chemical probes * inhibitors * intramembrane proteases * liposomes Subject RIV: CE - Biochemistry Impact factor: 2.850, year: 2015

  12. Enzyme sensitive liposomes in chemotherapy and potentiation of immunotherapy

    DEFF Research Database (Denmark)

    Østrem, Ragnhild Garborg

    efficacy and induction of severe adverse effects. Interestingly, the pharmacokinetics and biodistribution of drugs can be substantially altered by encapsulation in liposomal drug delivery vehicles. The first chapter of this thesis gives a brief introduction to cancer followed by a discussion...

  13. Radiation induced oxidative damage modification by cholesterol in liposomal membrane

    Energy Technology Data Exchange (ETDEWEB)

    Pandey, B.N. [Radiation Biology and Biochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai (India); Mishra, K.P. [Radiation Biology and Biochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai (India)

    1999-05-01

    Ionizing radiation induced structural and chemical alterations in egg lecithin liposomal membrane have been studied by measurements of lipid peroxides, conjugated diene and fluorescence polarization. Predominantly unilamellar phospholipid vesicles prepared by sonication procedure were subjected to radiation doses of {gamma}-rays from Co-60 in aerated, buffered aqueous suspensions. The oxidative damage in irradiated lipid molecules of liposomes has been determined spectrophotometrically by diene conjugate formation and thiobarbituric acid reactive (TBAR) method as a function of radiation dose. A correlation was found between the radiation dose applied (0.1-1 kGy) and the consequent lipid oxidation. The damage produced in irradiated liposomal membrane was measured by 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence decay and polarization. The observed decrease in DPH fluorescence and increase in polarization was found dependent on the radiation dose suggesting alterations in rigidity or organizational order in phospholipid bilayer after irradiation. Furthermore, irradiated liposome vesicles composed of cholesterol showed marked reduction in observed radiation mediated peroxide formation and significantly affected the DPH fluorescence parameters. The magnitude of these modifying effects were found dependent on the mole fraction of cholesterol. It is concluded that modulation of structural order in unilamellar vesicle membrane by variations in basic molecular components controlled the magnitude of lipid peroxidation and diene conjugate formation. These observations contribute to our understanding of mechanism of radical reaction mediated damage caused by ionizing radiation in phospholipid membrane.

  14. Vitamin C-driven epirubicin loading into liposomes

    Directory of Open Access Journals (Sweden)

    Lipka D

    2013-09-01

    Full Text Available Dominik Lipka,1 Jerzy Gubernator,1 Nina Filipczak,1 Sabine Barnert,2 Regine Süss,2 Mateusz Legut,1 Arkadiusz Kozubek1 1Department of Lipids and Liposomes, University of Wroclaw, Wroclaw, Poland; 2Department of Pharmaceutical Technology, Albert Ludwigs University, Freiburg, Germany Abstract: The encapsulation of anticancer drugs in a liposome structure protects the drug during circulation and increases drug accumulation in the cancer tissue and antitumor activity while decreasing drug toxicity. This paper presents a new method of active drug loading based on a vitamin C pH/ion gradient. Formulations were characterized in terms of the following parameters: optimal external pH, time and drug-to-lipid ratio for the purpose of remote loading, and in vitro stability. In the case of the selected drug, epirubicin (EPI, its coencapsulation increases its anticancer activity through a possibly synergistic effect previously reported by other groups for a free nonencapsulated drug/vitamin C cocktail. The method also has another advantage over other remote-loading methods: it allows faster drug release through liposome destabilization at the tumor site, thanks to the very good solubility of the EPI vitamin C salt, as seen on cryogenic transmission electron microscopy images. This influences the drug-release process and increases the anticancer activity of the liposome formulation. The liposomes are characterized as stable, with very good pharmacokinetics (half-life 18.6 hours. The antitumor activity toward MCF-7 and 4T-1 breast cancer cells was higher in the case of EPI loaded via our gradient than via an ammonium sulfate gradient. Finally, the EPI liposomal formulation and the free drug were tested using the murine 4T-1 breast cancer model. The antitumor activity of the encapsulated drug was confirmed (tumor-growth inhibition over 40% from day 16 until the end of the experiment, and the free drug was shown to have no anticancer activity at the tested dose

  15. Spontaneous stress fractures of the femoral neck

    International Nuclear Information System (INIS)

    Dorne, H.L.; Lander, P.H.

    1985-01-01

    The diagnosis of spontaneous stress fractures of the femoral neck, a form of insufficiency stress fracture, can be missed easily. Patients present with unremitting hip pain without a history of significant trauma or unusual increase in daily activity. The initial radiographic features include osteoporosis, minor alterations of trabecular alignment, minimal extracortical or endosteal reaction, and lucent fracture lines. Initial scintigraphic examinations performed in three of four patients showed focal increased radionuclide uptake in two and no focal abnormality in one. Emphasis is placed on the paucity of early findings. Evaluation of patients with persistent hip pain requires a high degree of clinical suspicion and close follow-up; the sequelae of undetected spontaneous fractures are subcapital fracture with displacement, angular deformity, and a vascular necrosis of the femoral head

  16. Motivational Projections of Russian Spontaneous Speech

    Directory of Open Access Journals (Sweden)

    Galina M. Shipitsina

    2017-06-01

    Full Text Available The article deals with the semantic, pragmatic and structural features of words, phrases, dialogues motivation, in the contemporary Russian popular speech. These structural features are characterized by originality and unconventional use. Language material is the result of authors` direct observation of spontaneous verbal communication between people of different social and age groups. The words and remarks were analyzed in compliance with the communication system of national Russian language and cultural background of popular speech. Studies have discovered that in spoken discourse there are some other ways to increase the expression statement. It is important to note that spontaneous speech identifies lacunae in the nominative language and its vocabulary system. It is proved, prefixation is also effective and regular way of the same action presenting. The most typical forms, ways and means to update language resources as a result of the linguistic creativity of native speakers were identified.

  17. Focused ultrasound influence on calcein-loaded thermosensitive stealth liposomes.

    Science.gov (United States)

    Novell, Anthony; Al Sabbagh, Chantal; Escoffre, Jean-Michel; Gaillard, Cédric; Tsapis, Nicolas; Fattal, Elias; Bouakaz, Ayache

    2015-06-01

    Focused ultrasound (FUS) is a versatile technology for non-invasive thermal therapies in oncology. Indeed, this technology has great potential for local heat-mediated drug delivery from thermosensitive liposomes (TSLs), thus improving therapeutic efficacy and reducing toxicity profiles. In the present study we evaluated the influence of FUS parameters on the release of calcein from TSLs used to model a hydrophilic drug. Quantitative calcein release from TSLs (DPPC/CHOL/DSPE-PEG2000: 90/5/5) and non-thermosensitive liposomes (NTSLs) (DPPC/CHOL/DSPE-PEG2000: 65/30/5) was measured by spectrofluorimetry after both water bath and FUS-induced in vitro heating. The heating of TSLs at 42 °C in a water bath resulted in a maximum calcein release of 45%. No additional calcein release was observed at temperatures above 42 °C. A similar percentage of calcein release was achieved when TSLs were exposed to 1 MHz sinusoidal waves at peak negative pressure of 1.5 MPa, 40% duty cycle, for 10 min (i.e. above 42 °C). No release was detected when NTSLs were heated in a water bath. For both TSLs and NTSLs, the calcein release was increased by more than 10% for acoustic pressures ranging from 1.5 MPa to 2 MPa. This additional release was attributed to the mechanical stress generated by FUS, which was sufficient to disrupt the liposomal membrane. Furthermore, analysis of cryo-TEM images showed a significant decrease in liposome size (14%) induced by the thermal effect, whereas the liposome diameter remained unaffected by the FUS-triggered non-thermal effects.

  18. Low level LED photodynamic therapy using curcumin loaded tetraether liposomes.

    Science.gov (United States)

    Duse, Lili; Pinnapireddy, Shashank Reddy; Strehlow, Boris; Jedelská, Jarmila; Bakowsky, Udo

    2017-10-07

    Oncological use of photodynamic therapy is an evolving field in cancer therapeutics. Photosensitisers are prone to accumulation inside healthy tissues causing undesirable effects. To avoid this, we have developed tetraether lipid liposomal formulations containing curcumin which is a naturally occurring anti-cancer substance and deemed to be safe towards healthy cells. Upon excitation with light at a specific wavelength, curcumin produces reactive oxygen species (ROS) in presence of oxygen, thereby exhibiting a cytotoxic effect towards the surrounding tissues, giving a total control on the onset of therapy. In our study, we examined two different liposomal formulations wherein curcumin is encapsulated within the hydrophobic milieu with the intent to increase its bioavailability. Hydrodynamic diameter, surface charge, stability, morphology and haemocompatibility of the liposomes were studied. The results confirmed the formation of stable nanometre range liposomal vesicles (200-220 nm) containing curcumin which were haemocompatible with coagulation time less than 50 s and a haemolytic potential below 40%. Increased ROS generation post irradiation (>50% compared to un-irradiated samples) was confirmed using fluorescence spectroscopy. The efficiency and selectivity of the PDT was demonstrated by assessing their viability post irradiation and by qualitative analysis using confocal microscopy showing nuclear perforation induced by PDT. Photo-destructive effects of PDT on the microvasculature were studied in vivo using chick chorioallantoic membrane model (CAM). Considerable phototoxicity could be observed in the irradiated area of the CAM 30 min post irradiation. Phototoxic effects in vitro (in SK-OV-3 and PCS-100-020™) and in vivo (in chorioallantoic membrane model) in combination with a novel custom manufactured LED irradiating device showed a formulation dependant selective photodynamic effect of the curcumin liposomes. Copyright © 2017 Elsevier B.V. All rights

  19. Silica nanoparticle coated liposomes: a new type of hybrid nanocapsule for proteins.

    Science.gov (United States)

    Mohanraj, Vellore J; Barnes, Timothy J; Prestidge, Clive A

    2010-06-15

    A hybrid silica-liposome nanocapsule system containing insulin has been developed and the encapsulation, protection and release properties are evaluated. The formulation strategy is based on using insulin-loaded 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and cholesterol liposomes as a template for the deposition of inert silica nanoparticles. The influence of formulation and process variables on particle size, zeta potential and liposome entrapment of insulin is reported. The ability to protect against lipolytic degradation and sustain insulin release in vitro in simulated GI conditions is also reported. Depending on the concentration and charge ratio of liposomes and silica nanoparticles, nanoparticle coated liposomes with varied size and zeta potential were obtained with an insulin entrapment efficiency of 70%. The silica nanoparticle coating protected liposomes against degradation by digestive enzymes in vitro; the release rate of insulin from silica coated liposomes was reduced in comparison to uncoated liposomes. Thus the liposomal release kinetics and stability can be controlled by including a specifically engineered nanoparticle layer. Silica nanoparticle-liposomes hybrid nanocapsules show promise as a delivery vehicle for proteins and peptides. Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.

  20. An evaluation of anti-tumor effect and toxicity of PEGylated ursolic acid liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qianqian; Zhao, Tingting; Liu, Yanping; Xing, Shanshan; Li, Lei; Gao, Dawei, E-mail: dwgao@ysu.edu.cn [Yanshan University, Applying Chemistry Key Lab of Hebei Province, Department of Bioengineer (China)

    2016-02-15

    Therapy of solid tumors mediated by nano-drug delivery has attracted considerable interest. In our previous study, ursolic acid (UA) was successfully encapsulated into PEGylated liposomes. The study aimed to evaluate the tumor inhibition effect and cytotoxicity of the PEGylated UA liposomes by U14 cervical carcinoma-bearing mice. The liposomes were spherical particles with mean particle diameters of 127.2 nm. The tumor inhibition rate of PEGylated UA liposomes was 53.60 % on U14 cervical carcinoma-bearing mice, which was greater than those of the UA solution (18.25 %) and traditional UA liposome groups (40.75 %). The tumor cells apoptosis rate of PEGylated UA liposomes was 25.81 %, which was significantly higher than that of the traditional UA liposomes (13.37 %). Moreover, the kidney and liver did not emerge the pathological changes in UA therapeutic mice by histopathological analysis, while there were significant differences on tumor tissues among three UA formulation groups. The PEGylated UA liposomes exhibited higher anti-tumor activity and lower cytotoxicity, and the main reason was that the coating PEG layer improved UA liposome properties, such as enhancing the stability of liposomes, promoting the effect of slow release, and prolonging the time of blood circulation. This may shed light on the development of PEGylated nano-vehicles.

  1. 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

    2016-06-06

    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.

  2. Zn2+Induced Irreversible Aggregation, Stacking, and Leakage of Choline Phosphate Liposomes.

    Science.gov (United States)

    Liu, Yibo; Liu, Juewen

    2017-12-19

    The interaction between lipids and metal ions is important for metal sensing, cellular signal transduction, and oxidative lipid damage. While most previous work overlooked the phosphate group of lipids for metal binding, we herein highlight its importance. Phosphocholine (PC) and its headgroup inversed choline phosphate (CP) lipids were used to prepare liposomes. From dynamic light scattering (DLS), Zn 2+ causes significant aggregation or fusion of the CP liposomes, but not PC liposomes. The size change induced by Zn 2+ is not fully reversed by adding EDTA, implying liposome fusion induced by Zn 2+ . Isothermal titration calorimetry (ITC) shows that binding between Zn 2+ and CP liposomes is endothermic with a K d of 110 μM Zn 2+ , suggesting an entropy driven reaction likely due to the release of bound water. In comparison, no heat was detected by titrating Zn 2+ into PC liposomes or Ca 2+ into CP liposomes. Furthermore, Zn 2+ causes a transient leakage of the CP liposomes, and further leakage is observed upon removing Zn 2+ by EDTA. Transmission electron microscopy (TEM) with negative stained samples showed multilamellar CP lipid structures attributable to Zn 2+ sandwiched between lipid bilayers, leading to a proposed reaction mechanism. This work provides an interesting system for studying metal interacting with terminal phosphate groups in liposomes, affecting the size, charge, and membrane integrity of the liposomes.

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

    Science.gov (United States)

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

    2004-04-13

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

  4. Binding and uptake of transferrin-bound liposomes targeted to transferrin receptors of endothelial cells.

    Science.gov (United States)

    Voinea, Manuela; Dragomir, Elena; Manduteanu, Ileana; Simionescu, Maya

    2002-07-01

    The use of liposomes as carriers for site-specific delivery is an attractive strategy, especially for the vascular endothelium that by position is an accessible target for drug and gene delivery via the blood circulation. The aim of this study was to detect whether liposomes coupled to transferrin (Tf)-bound and are taken up by aortic endothelial cells (EC) following the pathway of Tf interaction with transferrin receptors, reportedly expressed on their cell membrane. To this purpose, small unilamellar liposomes of different compositions, either classical (C) or sterically stabilized (SS), have been prepared, characterized and coupled with transferrin (Tf-liposomes). To assess the binding and uptake, cultured EC were incubated with fluorescently labelled Tf-liposomes for various times intervals (from 5 min to 24 h) at 4 and 37 degrees C, and further investigated by flow cytometry, fluorimetry and fluorescence microscopy. The results showed that: (i) binding of Tf-liposomes to EC was specific; (ii) the EC binding of SS-Tf-liposomes was lower than that of C-Tf-liposomes; and (iii) after 30 min of incubation, both C- and SS-Tf-liposomes appeared localized in the acidic compartments of the cells. Together, the data indicate that transferrin-bound liposomes are specifically taken up by EC by a receptor-mediated mechanism employing the pathway of surface-exposed Tf receptors.

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

    Directory of Open Access Journals (Sweden)

    Jes Dreier

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

  6. Macrophage depletion by clodronate liposome attenuates muscle injury and inflammation following exhaustive exercise

    Directory of Open Access Journals (Sweden)

    Noriaki Kawanishi

    2016-03-01

    Full Text Available Exhaustive exercise promotes muscle injury, including myofiber lesions; however, its exact mechanism has not yet been elucidated. In this study, we tested the hypothesis that macrophage depletion by pretreatment with clodronate liposomes alters muscle injury and inflammation following exhaustive exercise. Male C57BL/6J mice were divided into four groups: rest plus control liposome (n=8, rest plus clodronate liposome (n=8, exhaustive exercise plus control liposome (n=8, and exhaustive exercise plus clodronate liposome (n=8. Mice were treated with clodronate liposome or control liposome for 48 h before undergoing exhaustive exercise on a treadmill. Twenty-four hours after exhaustive exercise, the gastrocnemius muscles were removed for histological and PCR analyses. Exhaustive exercise increased the number of macrophages in the muscle; however, clodronate liposome treatment reduced this infiltration. Although exhaustive exercise resulted in an increase in injured myofibers, clodronate liposome treatment following exhaustive exercise reduced the injured myofibers. Clodronate liposome treatment also decreased the mRNA expression levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6 in the skeletal muscle after exhaustive exercise. These results suggest that macrophages play a critical role in increasing muscle injury by regulating inflammation.

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

    Science.gov (United States)

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

    2017-11-01

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

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

    Science.gov (United States)

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

    2017-11-01

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

  9. Teaching Form as Form

    DEFF Research Database (Denmark)

    Keiding, Tina Bering

    2012-01-01

    understanding of form per se, or, to use an expression from this text, of form as form. This challenge can be reduced to one question: how can design teaching support students in achieving not only the ability to recognize and describe different form-related concepts in existing design (i.e. analytical...... and concepts from real designs by studying form in abstract contexts. The challenge for the first approach is how to support students in decoupling form from the work as a whole. The challenge for the second approach is how to translate general form into real design. Hence, choosing between the two approaches...

  10. Silica-based monolithic capillary columns modified by liposomes for characterization of analyte–liposome interactions by capillary liquid chromatography

    Czech Academy of Sciences Publication Activity Database

    Moravcová, Dana; Planeta, Josef; Wiedmer, S. K.

    2013-01-01

    Roč. 1317, SI (2013), s. 159-166 ISSN 0021-9673 R&D Projects: GA MV VG20112015021; GA ČR(CZ) GAP206/11/0138 Institutional support: RVO:68081715 Keywords : monolithic silica capillary column * immobilized liposomes * biomimicking stationary phase Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 4.258, year: 2013

  11. Spontaneous breaking of supersymmetry

    Energy Technology Data Exchange (ETDEWEB)

    Zumino, B.

    1981-12-01

    There has been recently a revival of interest in supersymmetric gauge theories, stimulated by the hope that supersymmetry might help in clarifying some of the questions which remain unanswered in the so called Grand Unified Theories and in particular the gauge hierarchy problem. In a Grand Unified Theory one has two widely different mass scales: the unification mass M approx. = 10/sup 15/GeV at which the unification group (e.g. SU(5)) breaks down to SU(3) x SU(2) x U(1) and the mass ..mu.. approx. = 100 GeV at which SU(2) x U(1) is broken down to the U(1) of electromagnetism. There is at present no theoretical understanding of the extreme smallness of the ratio ..mu../M of these two numbers. This is the gauge hierarchy problem. This lecture attempts to review the various mechanisms for spontaneous supersymmetry breaking in gauge theories. Most of the discussions are concerned with the tree approximation, but what is presently known about radiative correction is also reviewed.

  12. Spontaneous intracranial hypotension

    International Nuclear Information System (INIS)

    Haritanti, A.; Karacostas, D.; Drevelengas, A.; Kanellopoulos, V.; Paraskevopoulou, E.; Lefkopoulos, A.; Economou, I.; Dimitriadis, A.S.

    2009-01-01

    Spontaneous intracranial hypotension (SIH) is an uncommon but increasingly recognized syndrome. Orthostatic headache with typical findings on magnetic resonance imaging (MRI) are the key to diagnosis. Delayed diagnosis of this condition may subject patients to unnecessary procedures and prolong morbidity. We describe six patients with SIH and outline the important clinical and neuroimaging findings. They were all relatively young, 20-54 years old, with clearly orthostatic headache, minimal neurological signs (only abducent nerve paresis in two) and diffuse pachymeningeal gadolinium enhancement on brain MRI, while two of them presented subdural hygromas. Spinal MRI was helpful in detecting a cervical cerebrospinal fluid leak in three patients and dilatation of the vertebral venous plexus with extradural fluid collection in another. Conservative management resulted in rapid resolution of symptoms in five patients (10 days-3 weeks) and in one who developed cerebral venous sinus thrombosis, the condition resolved in 2 months. However, this rapid clinical improvement was not accompanied by an analogous regression of the brain MR findings that persisted on a longer follow-up. Along with recent literature data, our patients further point out that SIH, to be correctly diagnosed, necessitates increased alertness by the attending physician, in the evaluation of headaches

  13. Spontaneous lateral temporal encephalocele.

    Science.gov (United States)

    Tuncbilek, Gokhan; Calis, Mert; Akalan, Nejat

    2013-01-01

    A spontaneous encephalocele is one that develops either because of embryological maldevelopment or from a poorly understood postnatal process that permits brain herniation to occur. We here report a rare case of lateral temporal encephalocele extending to the infratemporal fossa under the zygomatic arch. At birth, the infant was noted to have a large cystic mass in the right side of the face. After being operated on initially in another center in the newborn period, the patient was referred to our clinic with a diagnosis of temporal encephalocele. He was 6 months old at the time of admission. Computerized tomography scan and magnetic resonance imaging studies revealed a 8 × 9 cm fluid-filled, multiloculated cystic mass at the right infratemporal fossa. No intracranial pathology or connection is seen. The patient was operated on to reduce the distortion effect of the growing mass. The histopathological examination of the sac revealed well-differentiated mature glial tissue stained with glial fibrillary acid protein. This rare clinical presentation of encephaloceles should be taken into consideration during the evaluation of the lateral facial masses in the infancy period, and possible intracranial connection should be ruled out before surgery to avoid complications.

  14. Bilateral spontaneous carotid artery dissection.

    Science.gov (United States)

    Townend, Bradley Scott; Traves, Laura; Crimmins, Denis

    2005-06-01

    Bilateral internal carotid artery dissections have been reported, but spontaneous bilateral dissections are rare. Internal carotid artery dissection can present with a spectrum of symptoms ranging from headache to completed stroke. Two cases of spontaneous bilateral carotid artery dissection are presented, one with headache and minimal symptoms and the other with a stroke syndrome. No cause could be found in either case, making the dissections completely spontaneous. Bilateral internal carotid artery dissection (ICAD) should be considered in young patients with unexplained head and neck pain with or without focal neurological symptoms and signs. The increasing availability of imaging would sustain the higher index of suspicion.

  15. Application of 10B entrapped PEG-liposome to boron neutron-capture therapy for pancreatic cancer model in vivo

    International Nuclear Information System (INIS)

    Yanagie, H.; Eriguchi, M.; Maruyama, K.; Takizawa, T.; Ishida, O.; Ogura, K.; Matsumoto, T.; Sakurai, Y.; Kobayashi, T.; Ono, K.; Rant, J.; Skvarc, J.; Ilic, R.; Shinohara, A.; Chiba, M.; Kobayashi, H.

    1999-01-01

    The cytotoxic effects for tumor were evaluated with intravenous injection 10 B PEG-liposome (Stealth liposome) on human pancreatic carcinoma wenografts in nude mice with thermal neutron irradiation. After thermal neutron irradiation of mice injected with 10 B bare-liposome or 10 B PEG liposome, AsPC-1 tumour growth was suppressed relative to controls. Injection of 10 B PEG-liposome caused the greatest tumour suppression with thermal neutron irradiation in vivo. These results suggest that intravenous injection of 10 B PEG-liposome can increase the retention of 10 B atoms by tumor cells, causing tumor growth suppression in vivo upon thermal neutron irradiation.(author)

  16. Spontaneous Breaking of Spatial and Spin Symmetry in Spinor Condensates

    DEFF Research Database (Denmark)

    Scherer, M.; Lücke, B.; Gebreyesus, G.

    2010-01-01

    Parametric amplification of quantum fluctuations constitutes a fundamental mechanism for spontaneous symmetry breaking. In our experiments, a spinor condensate acts as a parametric amplifier of spin modes, resulting in a twofold spontaneous breaking of spatial and spin symmetry in the amplified...... broken, but phase squeezing prevents spin-symmetry breaking. If, however, nondegenerate spin modes contribute to the amplification, quantum interferences lead to spin-dependent density profiles and hence spontaneously formed patterns in the longitudinal magnetization....... clouds. Our experiments permit a precise analysis of the amplification in specific spatial Bessel-like modes, allowing for the detailed understanding of the double symmetry breaking. On resonances that create vortex-antivortex superpositions, we show that the cylindrical spatial symmetry is spontaneously...

  17. Physicochemical characterization of liposomes after ultrasound exposure - mechanisms of drug release

    DEFF Research Database (Denmark)

    Evjen, Tove J; Hupfeld, Stefan; Barnert, Sabine

    2013-01-01

    -mediated drug release of liposomes (sonosensitivity) was shown to strongly depend on liposome membrane composition. In the current study the ultrasound-mediated drug release mechanism of liposomes was investigated. The results showed that differences in ultrasound drug release kinetics obtained for different......Ultrasound is investigated as a novel drug delivery tool within cancer therapy. Non-thermal ultrasound treatment of solid tumours post i.v.-injection of drug-carrying liposomes may induce local drug release from the carrier followed by enhanced intracellular drug uptake. Recently, ultrasound...... liposomal compositions were caused by distinctive release mechanisms of the carriers. Two types of liposomes composed of 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE) and hydrogenated soy L-α-phosphatidylcholine (HSPC) as main lipids, respectively, were recently shown to vary in sonosensitivity...

  18. Anti-listeria effects of chitosan-coated nisin-silica liposome on Cheddar cheese.

    Science.gov (United States)

    Cui, H Y; Wu, J; Li, C Z; Lin, L

    2016-11-01

    Listeria monocytogenes poses an increasing challenge to cheese production. To minimize the risk of bacterial contamination, a chitosan-coated nisin-silica liposome was engineered for the present study. We investigated the characteristics of nisin-silica liposomes and the anti-listeria effects of a chitosan-coated nisin-silica liposome on Cheddar cheese. The encapsulation efficiency of nisin in a liposome was sharply increased after it was adsorbed on a silica particle surface. Chitosan-coated nisin-silica liposomes displayed sustained antibacterial activity against L. monocytogenes, without affecting the sensory properties of the cheese. Chitosan-coated nisin-silica liposomes could be a promising active antimicrobial for cheese preservation. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  19. Oral administration of insulin by means of liposomes in animal experiments

    International Nuclear Information System (INIS)

    Tragl, K.H.; Pohl, A.; Kinast, H.

    1979-01-01

    Liposomes are an effective vehicle for the oral administration of insulin. They are prepared from lipid emulsions by sonication and particles of homogeneous size are generated by elution through sepharose columns. Liposomes are taken up into the gastric mucosa by endocytosis and then transported to the liver via the portal circulation. Oral administration of 10 U insulin/kg body weight to rats is followed by a reduction in blood glucose to 67% of the initial value. When liposome-trapped insulin was injected intravenously a decrease in blood glucose to 40% of the initial value was obtained by the administration of 5 IU insulin/kg body weight. While the effect of orally-administered liposome-trapped insulin is obvious, the problems of standardization of the insulin content of the liposomes and the great variability of liposome uptake into the gastric mucosa by endocytosis remain unsolved. (author)

  20. 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

    2012-06-06

    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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. The in vitro characterisation and biodistribution of some non-ionic surfactant coated liposomes in the rabbit.

    Science.gov (United States)

    Khattab, M A; Farr, S J; Taylor, G; Kellaway, I W

    1995-01-01

    The degree of adsorption of some novel silicone glycol copolymers onto polystyrene microspheres was studied and compared with the sorption onto small unilamellar vesicles (SUVs) composed of egg phosphatidylcholine (EPC) and prepared by the detergent dialysis technique. These non-ionic surfactants are 'comb' polymers of the ABn type where A is a silicone chain with n pendant polyglycol chains (B). Photon correlation spectroscopy was used to measure the adsorbed layer thickness (delta h) following polymer sorption from aqueous solutions. delta h on latex particles was a function of the length of the polymer hydrophilic chains. Upon incubation with SUVs, delta h of the different polymers was similar (3 nm) and significantly less (two sample t-test, p coated with the silicone polymer possessing the highest glycol content and the longest ethylene oxide chains. Sterically stabilised vesicles were also formed by coating dipalmitoyl phosphatidyl-choline (DPPC)/cholesterol (Chol) (molar ratio 1:1) with two of these silicone glycol copolymers and Poloxamer 338. The liposomes were labelled with 67gallium-desferrioxamine (67Ga-DF). Incubation of radiolabelled Poloxamer 338-coated vesicles in saline or serum at 37 degrees C for 24 h resulted in less stable liposomes compared to the more stable non-coated or silicone coated vesicles. Following intravenous (i.v.) administration in rabbits, free 67Ga-DF rapidly disappeared from the circulation (half-life = 41.4 min) and accumulated in the bladder. Two populations of vesicles were prepared (136 +/- 2.9 nm and 100 +/- 1.4 nm). 24 h after i.v. injection of the different formulations of the 100 nm liposomes in rabbits, 20-27% of the activity was retained in blood. The silicone polymer with the highest glycol content and the longest ethylene oxide chains showed the longest half-life (21.4 h). Using gamma scintigraphy, the liver/spleen uptake of the 136 nm non-coated vesicles was 57% which was significantly reduced to 37% upon coating

  2. Lactosylated liposomes for targeted delivery of doxorubicin to hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Zhou X

    2012-10-01

    Full Text Available Xiaoju Zhou,1,2,* Mengzi Zhang,2,* Bryant Yung,2 Hong Li,2 Chenguang Zhou,2 L James Lee,3,4 Robert J Lee2,41State Key Laboratory of Virology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University School of Pharmaceutical Sciences, Wuhan, People’s Republic of China; 2Division of Pharmaceutics, 3Department of Chemical and Biomolecular Engineering, 4NSF Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, Columbus, OH, USA*These authors contributed equally to this workBackground: N-lactosyl-dioleoylphosphatidylethanolamine (Lac-DOPE was synthesized and evaluated as a liver-specific targeting ligand via asialoglycoprotein receptors for liposomal delivery of doxorubicin.Methods: Lactosylated liposomes encapsulating calcein (Lac-L-calcein or doxorubicin (Lac-L-DOX composed of egg phosphatidylcholine, cholesterol, monomethoxy polyethylene glycol 2000-distearoyl phosphatidylethanolamine, and Lac-DOPE at 50:35:5:10 (mol/mol were prepared by polycarbonate membrane extrusion and evaluated in human hepatocellular carcinoma HepG2 cells. Cellular uptake of Lac-L-calcein was monitored by confocal microscopy and by flow cytometry. The cytotoxicity of Lac-L-DOX was evaluated by MTT assay. The pharmacokinetic properties of Lac-L-DOX were studied in normal mice, and its biodistribution and antitumor activity were studied in nude mice with HepG2 xenografts.Results: The size of Lac-L-DOX was less than 100 nm and the liposomes demonstrated excellent colloidal stability. In vitro uptake of Lac-L-calcein by HepG2 cells was four times greater than that of non-targeted L-calcein. In the presence of 20 mM lactose, the uptake of Lac-L-calcein was inhibited, suggesting that asialoglycoprotein receptors mediated the observed cellular uptake. Lac-L-DOX exhibited enhanced in vivo cytotoxicity compared with the nontargeted liposomal doxorubicin (L

  3. Spontaneous intraorbital hematoma: case report

    Directory of Open Access Journals (Sweden)

    Vinodan Paramanathan

    2010-12-01

    Full Text Available Vinodan Paramanathan, Ardalan ZolnourianQueen's Hospital NHS Foundation Trust, Burton on Trent, Staffordshire DE13 0RB, UKAbstract: Spontaneous intraorbital hematoma is an uncommon clinical entity seen in ophthalmology practice. It is poorly represented in the literature. Current evidence attributes it to orbital trauma, neoplasm, vascular malformations, acute sinusitis, and systemic abnormalities. A 65-year-old female presented with spontaneous intraorbital hematoma manifesting as severe ocular pains, eyelid edema, proptosis, and diplopia, without a history of trauma. Computer tomography demonstrated a fairly well defined extraconal lesion with opacification of the paranasal sinuses. The principal differential based on all findings was that of a spreading sinus infection and an extraconal tumor. An unprecedented finding of a spontaneous orbital hematoma was discovered when the patient was taken to theater. We discuss the rarity of this condition and its management.Keywords: hemorrhage, ophthalmology, spontaneous, intra-orbital, hematoma

  4. Acoustic Studies on Nanodroplets, Microbubbles and Liposomes

    Science.gov (United States)

    Kumar, Krishna Nandan

    in vitro study aimed at developing an ultrasound-aided noninvasive pressure estimation technique using contrast agents-DefinityRTM, a lipid coated microbubble, and an experimental PLA (Poly lactic acid) microbubbles. Scattered responses from these bubbles have been measured in vitro as a function of ambient pressure using a 3.5 MHz acoustic excitation of varying amplitude. At an acoustic pressure of 670 kPa, Definity RTM microbubbles showed a linear decrease in subharmonic signal with increasing ambient pressure, registering a 12dB reduction at an overpressure of 120 mm Hg. Ultrasound contrast microbubbles experience widely varying ambient blood pressure in different organs, which can also change due to diseases. Pressure change can alter the material properties of the encapsulation of these microbubbles. Here the characteristic rheological parameters of contrast agent Definity and Targestar are determined by varying the ambient pressure (in a physiologically relevant range 0-200 mmHg). Four different interfacial rheological models are used to characterize the microbubbles. Both the contrast agents show an increase in their interfacial dilatational viscosity and interfacial dilatational elasticity with ambient pressure. It has been well established that liposomes prepared following a careful multi-step procedure can be made echogenic. Our group as well as others experimentally demonstrated that freeze-drying in the presence of mannitol is a crucial component to ensure echogenicity. Here, we showed that freeze-dried aqueous solutions of excipients such as mannitol, meso-erythritol, glycine, and glucose that assume a crystalline state, when dispersed in water creates bubbles and are echogenic even without any lipids. We also present an explanation for the bubble generation process because of dissolution of mannitol.

  5. The pharmacokinetics of, and humoral responses to, antigen delivered by microencapsulated liposomes.

    OpenAIRE

    Cohen, S; Bernstein, H; Hewes, C; Chow, M; Langer, R

    1991-01-01

    The feasibility of creating a s.c. depot for sustained protein delivery with the goal of enhancing antigen immunogenicity was investigated. The depot was designed as antigen-laden liposomes of hydrogenated egg phosphatidylcholine and cholesterol (1:1 molar ratio) encapsulated in alginate-poly(L-lysine) microcapsules and evaluated using iodinated bovine serum albumin (BSA) as a model antigen. The in vivo release behavior of the liposomes and microencapsulated liposomes (MELs) was evaluated fro...

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

    OpenAIRE

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

    2016-01-01

    Background The use of liposomes as drug delivery systems is the most promising technique for targeting drug especially for anticancer therapy. Methods In this study sterically stabilized liposomes was prepared from DPPC/Cholesterol/PEG-PE encapsulated doxorubicin. The effect of lyophilization on liposomal stability and hence expiration date were studied. Moreover, the effect of diode laser on the drug released from liposomesin vitro and in vivo in mice carrying implanted solid tumor were also...

  7. The Physical Characterization of Liposome Salicylic Acid Using Transmission Electron Microscope

    International Nuclear Information System (INIS)

    Elman Panjaitan

    2008-01-01

    The physical characterization of liposome, formulated from salicylic acid using thin film hydration methods with cholesterol and soybean lecithin, has been done. The formula was characterized by optical microscopes and Transmission Electron Microscope (TEM). The observation result shows that the salicylic acid can be formulated to liposomes. Soybean lecithin combined with cholesterol (600 mg : 20 mg) was the best formula and the liposome was spherical vesicle like with dimension about 70 nm unit 800 nm. (author)

  8. Spontaneous ischaemic stroke in dogs

    DEFF Research Database (Denmark)

    Gredal, Hanne Birgit; Skerritt, G. C.; Gideon, P.

    2013-01-01

    Translation of experimental stroke research into the clinical setting is often unsuccessful. Novel approaches are therefore desirable. As humans, pet dogs suffer from spontaneous ischaemic stroke and may hence offer new ways of studying genuine stroke injury mechanisms.......Translation of experimental stroke research into the clinical setting is often unsuccessful. Novel approaches are therefore desirable. As humans, pet dogs suffer from spontaneous ischaemic stroke and may hence offer new ways of studying genuine stroke injury mechanisms....

  9. Spontaneity and international marketing performance

    OpenAIRE

    Souchon, Anne L.; Hughes, Paul; Farrell, Andrew M.; Nemkova, Ekaterina; Oliveira, Joao S.

    2016-01-01

    The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Purpose – The purpose of this paper is to ascertain how today’s international marketers can perform better on the global scene by harnessing spontaneity. Design/methodology/approach – The authors draw on contingency theory to develop a model of the spontaneity – international marketing performance relationship, and identify three potential m...

  10. Aerosolized liposomes with dipalmitoyl phosphatidylcholine enhance pulmonary absorption of encapsulated insulin compared with co-administered insulin.

    Science.gov (United States)

    Chono, Sumio; Togami, Kohei; Itagaki, Shirou

    2017-11-01

    We have previously shown that aerosolized liposomes with dipalmitoyl phosphatidylcholine (DPPC) enhance the pulmonary absorption of encapsulated insulin. In this study, we aimed to compare insulin encapsulated into the liposomes versus co-administration of empty liposomes and unencapsulated free insulin, where the DPCC liposomes would serve as absorption enhancer. The present study provides the useful information for development of noninvasive treatment of diabetes. Co-administration of empty DPPC liposomes and unencapsulated free insulin was investigated in vivo to assess the potential enhancement in protein pulmonary absorption. Co-administration was compared to DPPC liposomes encapsulating insulin, and free insulin. DPPC liposomes enhanced the pulmonary absorption of unencapsulated free insulin; however, the enhancing effect was lower than that of the DPPC liposomes encapsulating insulin. The mechanism of the pulmonary absorption of unencapsulated free insulin by DPPC liposomes involved the opening of epithelial cell space in alveolar mucosa, and not mucosal cell damage, similar to that of the DPPC liposomes encapsulating insulin. In an in vitro stability test, insulin in the alveolar mucus layer that covers epithelial cells was stable. These findings suggest that, although unencapsulated free insulin spreads throughout the alveolar mucus layer, the concentration of insulin released near the absorption surface is increased by the encapsulation of insulin into DPPC liposomes and the absorption efficiency is also increased. We revealed that the encapsulation of insulin into DPPC liposomes is more effective for pulmonary insulin absorption than co-administration of DPPC liposomes and unencapsulated free insulin.

  11. Liposomal Doxorubicin Delivery Systems: Effects of Formulation and Processing Parameters on Drug Loading and Release Behavior.

    Science.gov (United States)

    Mohammadi, Zahra Ali; Aghamiri, Seyed Foad; Zarrabi, Ali; Talaie, Mohammad Reza

    2016-01-01

    Liposomes can serve as promising carriers for targeting delivery and controlled release of anti-cancer drugs. Doxorubicin-loaded liposomes have achieved enhanced efficacy in some solid tumors due to EPR effect with prolonged circulation and reduced toxicity. In this study the effects of liposomal structure have been investigated on the loading efficiency and controlled release behavior. Liposomes with various compositions were prepared through a thin film hydration method, and extruded to large unilamellar vesicles (LUVs) with mean particle size (Z ave~ 100 nm) by high-pressure extrusion technique. Then, doxorubicin was loaded into liposomes using remote active loading strategy. The loading efficiency and drug release behavior were evaluated using various parameters such as medium pH, liposome compositions and cholesterol concentrations. Liposomes prepared with different compositions showed high levels of drug encapsulation. Drug loading efficiencies (>90%) achieved with high final drug/lipid ratio (0.18-0.2). Faster release was observed at pH 5.5 when compared to pH 7.4 for all formulations. The fastest release rate was observed for unsaturated lipid (<48hr) and the slowest release rate was observed for saturated lipids with high phase transition temperature such as 1, 2-distearoylphosphatidylcholine (DSPC) and hydrogenated soy phosphatidylcholine (HSPC) (10-18 days). The sustained release was observed for liposomal formulations containing cholesterol. In conclusion, we have demonstrated that drug release rate could be controlled by manipulating the composition of liposomal structures.

  12. Gold nanoparticles decorated liposomes and their SERS performance in tumor cells

    Science.gov (United States)

    Zhu, D.; Wang, Z. Y.; Zong, S. F.; Chen, H.; Chen, P.; Li, M. Y.; Wu, L.; Cui, Y. P.

    2015-05-01

    Due to their unique properties, liposomes have been widely used as drug nanocarriers. Herein a liposome-Au nanohybrid has been demonstrated as a SERS active intracellular drug nanocarrier. In this study, cationic Raman reporter tagged gold nanoparticles (Au@4MBA@PAH) were anchored onto the surfaces of anionic liposomes via electrostatic interactions. Using SKBR3 cells as model cells, we revealed that the hybrid formulation can be effectively taken up by tumor cells and tracked by the SERS signals. Collectively, the liposome-Au nanohybrids hold great promise in biomedical applications.

  13. Morphology and bilayer integrity of small liposomes during aerosol generation by air-jet nebulisation

    Energy Technology Data Exchange (ETDEWEB)

    Chattopadhyay, Saptarshi [Indian Institute of Technology-Bombay, Department of Chemical Engineering (India); Ehrman, Sheryl H. [University of Maryland, Department of Chemical and Biomolecular Engineering (United States); Bellare, Jayesh; Venkataraman, Chandra, E-mail: chandra@iitb.ac.in [Indian Institute of Technology-Bombay, Department of Chemical Engineering (India)

    2012-03-15

    Small liposome suspensions (hydrodynamic diameter, 80-130 nm) were nebulised, and the resulting changes in morphology and bilayer integrity were found to be related to surface properties controlled by bilayer composition. Four separate liposome compositions (or liposome types) were investigated using three different phospholipids with unique properties. Morphological changes were studied using light scattering and imaging of liposomes before and after nebulisation, and structural integrity was investigated on the basis of the retention of an encapsulated dye (probe molecule). Nebulisation generated droplets contained liposomes. The liposome particles generated on droplet evaporation had a hollow structure as evidenced by electron imaging, indicating that the lipid bilayer does not collapse on evaporation. The particles of all compositions had mobility diameters between 50 and 90 nm, 1.4-1.6 times smaller than their diameters (hydrodynamic) measured before nebulisation, implying considerable volume shrinkage. Liposomes that had polymer-conjugated lipids covering their external surface underwent aggregation during nebulisation, evidenced by increased diameter after nebulisation. Incorporation of charged lipids reduced nebulisation-induced aggregation, but induced greater membrane rupture during aerosol generation, causing leakage of encapsulated probe molecules. Incorporation of both cholesterol and charged lipids prevented aggregation, but also preserved bilayer integrity, evidenced by the maximum retention of encapsulated dye observed in these conditions (>85%). The findings suggest that liposome bilayer composition can be manipulated to improve the efficiency of liposome aerosol delivery.

  14. Morphology and bilayer integrity of small liposomes during aerosol generation by air-jet nebulisation

    International Nuclear Information System (INIS)

    Chattopadhyay, Saptarshi; Ehrman, Sheryl H.; Bellare, Jayesh; Venkataraman, Chandra

    2012-01-01

    Small liposome suspensions (hydrodynamic diameter, 80–130 nm) were nebulised, and the resulting changes in morphology and bilayer integrity were found to be related to surface properties controlled by bilayer composition. Four separate liposome compositions (or liposome types) were investigated using three different phospholipids with unique properties. Morphological changes were studied using light scattering and imaging of liposomes before and after nebulisation, and structural integrity was investigated on the basis of the retention of an encapsulated dye (probe molecule). Nebulisation generated droplets contained liposomes. The liposome particles generated on droplet evaporation had a hollow structure as evidenced by electron imaging, indicating that the lipid bilayer does not collapse on evaporation. The particles of all compositions had mobility diameters between 50 and 90 nm, 1.4–1.6 times smaller than their diameters (hydrodynamic) measured before nebulisation, implying considerable volume shrinkage. Liposomes that had polymer-conjugated lipids covering their external surface underwent aggregation during nebulisation, evidenced by increased diameter after nebulisation. Incorporation of charged lipids reduced nebulisation-induced aggregation, but induced greater membrane rupture during aerosol generation, causing leakage of encapsulated probe molecules. Incorporation of both cholesterol and charged lipids prevented aggregation, but also preserved bilayer integrity, evidenced by the maximum retention of encapsulated dye observed in these conditions (>85%). The findings suggest that liposome bilayer composition can be manipulated to improve the efficiency of liposome aerosol delivery.

  15. Physical and Oxidative Stability of Uncoated and Chitosan-Coated Liposomes Containing Grape Seed Extract

    Directory of Open Access Journals (Sweden)

    Jochen Weiss

    2013-08-01

    Full Text Available Polyphenol-rich grape seed extract (0.1 w/w% was incorporated in liposomes (1 w/w% soy lecithin by high pressure homogenization (22,500 psi and coated with chitosan (0.1 w/w%. Primary liposomes and chitosan-coated secondary liposomes containing grape seed extract showed good physical stability during 98 days of storage. Most of the polyphenols were incorporated in the shell of the liposomes (85.4%, whereas only 7.6% of the polyphenols of grape seed extract were located in the interior of the liposomes. Coating with chitosan did not change the polyphenol content in the liposomes (86.6%. The uncoated liposomes without grape seed extract were highly prone to lipid oxidation. The cationic chitosan coating, however, improved the oxidative stability to some extent, due to its ability to repel pro-oxidant metals. Encapsulated grape seed extract showed high antioxidant activity in both primary and secondary liposomes, which may be attributed to its polyphenol content. In conclusion, the best chemical stability of liposomes can be achieved using a combination of grape seed extract and chitosan.

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

    Science.gov (United States)

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

    2017-06-01

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

  17. Optimization on Preparation Conditions of Salidroside Liposome and Its Immunological Activity on PCV-2 in Mice

    Directory of Open Access Journals (Sweden)

    Yibo Feng

    2015-01-01

    Full Text Available The aim of this study was to optimize the preparation conditions of salidroside liposome with high encapsulation efficiency (EE and to study the immunological enhancement activity of salidroside liposome as porcine circovirus type 2 virus (PCV-2 vaccine adjuvant. Response surface methodology (RSM was selected to optimize the conditions for the preparation of salidroside liposome using Design-Expert V8.0.6 software. Three kinds of salidroside liposome adjuvants were prepared to study their adjuvant activity. BALB/c mice were immunized with PCV-2 encapsulated in different kinds of salidroside liposome adjuvants. The PCV-2-specific IgG in immunized mice serum was determined with ELISA. The results showed that when the concentration of ammonium sulfate was 0.26 mol·L−1, ethanol volume 6.5 mL, temperature 43°C, ethanol injection rate 3 mL·min−1, and salidroside liposome could be prepared with high encapsulation efficiency of 94.527%. Salidroside liposome as adjuvant could rapidly induce the production of PCV-2-specific IgG and salidroside liposome I adjuvant proved to provide the best effect among the three kinds of salidroside liposome adjuvants.

  18. Undulating tubular liposomes through incorporation of a synthetic skin ceramide into phospholipid bilayers.

    Science.gov (United States)

    Xu, Peng; Tan, Grace; Zhou, Jia; He, Jibao; Lawson, Louise B; McPherson, Gary L; John, Vijay T

    2009-09-15

    Nonspherical liposomes were prepared by doping L-alpha-phosphatidylcholine (PC) with ceramide VI (a skin lipid). Cryo-transmission electron microscopy shows the liposome shape changing from spherical to an undulating tubular morphology, when the amount of ceramide VI is increased. The formation of tubular liposomes is energetically favorable and is attributed to the association of ceramide VI with PC creating regions of lower curvature. Since ceramides are the major component of skin lipids in the stratum corneum, tubular liposomes containing ceramide may potentially serve as self-enhanced nanocarriers for transdermal delivery.

  19. Observation of inhomogeneity in the lipid composition of individual nanoscale liposomes

    DEFF Research Database (Denmark)

    Larsen, Jannik; Hatzakis, Nikos; Stamou, Dimitrios

    2011-01-01

    Liposomes, or vesicles, have been studied extensively both as models of biological membranes and as drug delivery vehicles. Typically it is assumed that all liposomes within the same preparation are identical. Here by employing pairs of fluorescently labeled lipids we demonstrated an up to 10-fold...... variation in the relative lipid composition of individual liposomes with diameters between 50 nm and 15 µm. Since the physicochemical properties of liposomes are directly linked to their composition, a direct consequence of compositional inhomogeneities is a polydispersity in the properties...

  20. Determination of platinum drug release and liposome stability in human plasma by CE-ICP-MS

    DEFF Research Database (Denmark)

    Nguyen, Trinh Thi Nhu Tam; Ostergaard, Jesper; Stürup, Stefan

    2013-01-01

    by sonication was also demonstrated. Analysis of liposomal formulations with alternative phospholipid compositions containing oxaliplatin showed similar results. Thus, the present in vitro method is suitable for mimicking the in vivo drug release profile in human plasma after administration of liposomal...... of the encapsulation efficiency of the formulation, the physical stability of liposomes as well as cisplatin leakage in human plasma. The method was applied for studying the disintegration of liposomes and the interactions of leaked cisplatin with plasma components. Triggered release of the drug into plasma...... platinum formulations to patients. This approach may be of use in early drug development as well as in quality control....

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

    Science.gov (United States)

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

    2013-10-01

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

  2. Multifunctional liposomes for nasal delivery of the anti-Alzheimer drug tacrine hydrochloride

    DEFF Research Database (Denmark)

    Corace, Giuseppe; Angeloni, Cristina; Malaguti, Marco

    2014-01-01

    Abstract The purpose of this study was the development of multifunctional liposomes for nasal administration of tacrine hydrochloride. Liposomes were prepared using traditional excipients (cholesterol and phosphatidylcholine), partly enriched with α-tocopherol and/or Omega3 fatty acids...... permeability, which can be related to liposome fusion with cellular membrane, a hypothesis, which was also supported by cellular uptake studies. Finally, the addition of α-tocopherol without Omega3 fatty acids, was found to increase the neuroprotective activity and antioxidant properties of liposomes....

  3. Biological Atomic Force Microscopy for Imaging Gold-Labeled Liposomes on Human Coronary Artery Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Ana-María Zaske

    2013-01-01

    Full Text Available Although atomic force microscopy (AFM has been used extensively to characterize cell membrane structure and cellular processes such as endocytosis and exocytosis, the corrugated surface of the cell membrane hinders the visualization of extracellular entities, such as liposomes, that may interact with the cell. To overcome this barrier, we used 90 nm nanogold particles to label FITC liposomes and monitor their endocytosis on human coronary artery endothelial cells (HCAECs in vitro. We were able to study the internalization process of gold-coupled liposomes on endothelial cells, by using AFM. We found that the gold-liposomes attached to the HCAEC cell membrane during the first 15–30 min of incubation, liposome cell internalization occurred from 30 to 60 min, and most of the gold-labeled liposomes had invaginated after 2 hr of incubation. Liposomal uptake took place most commonly at the periphery of the nuclear zone. Dynasore monohydrate, an inhibitor of endocytosis, obstructed the internalization of the gold-liposomes. This study showed the versatility of the AFM technique, combined with fluorescent microscopy, for investigating liposome uptake by endothelial cells. The 90 nm colloidal gold nanoparticles proved to be a noninvasive contrast agent that efficiently improves AFM imaging during the investigation of biological nanoprocesses.

  4. Scrapie prion liposomes and rods exhibit target sizes of 55,000 Da

    Energy Technology Data Exchange (ETDEWEB)

    Bellinger-Kawahara, C.G.; Kempner, E.; Groth, D.; Gabizon, R.; Prusiner, S.B.

    1988-06-01

    Scrapie is a degenerative neurologic disease in sheep and goats which can be experimentally transmitted to laboratory rodents. Considerable evidence suggests that the scrapie agent is composed largely, if not entirely, of an abnormal isoform of the prion protein (PrPSc). Inactivation of scrapie prions by ionizing radiation exhibited single-hit kinetics and gave a target size of 55,000 +/- 9000 mol wt. The inactivation profile was independent of the form of the prion. Scrapie agent infectivity in brain homogenates, microsomal fractions, detergent-extracted microsomes, purified amyloid rods, and liposomes exhibited the same inactivation profile. Our data are consistent with the hypothesis that the infectious particle causing scrapie contains approximately 2 PrPSc molecules.

  5. Identification of Unknown Impurity of Azelaic Acid in Liposomal Formulation Assessed by HPLC-ELSD, GC-FID, and GC-MS

    OpenAIRE

    Han, Stanisław; Karłowicz-Bodalska, Katarzyna; Potaczek, Piotr; Wójcik, Adam; Ozimek, Łukasz; Szura, Dorota; Musiał, Witold

    2013-01-01

    The identification of new contaminants is critical in the development of new medicinal products. Many impurities, such as pentanedioic acid, hexanedioic acid, heptanedioic acid, octanedioic acid, decanedioic acid, undecanedioic acid, dodecanedioic acid, tridecanedioic acid, and tetradecanedioic acid, have been identified in samples of azelaic acid. The aim of this study was to identify impurities observed during the stability tests of a new liposomal dosage form of azelaic acid that is compos...

  6. Reversible ototoxicity: a rare adverse reaction of liposomal amphotericin-B used for the treatment of antimony-resistant visceral leishmaniasis in an elderly male.

    Science.gov (United States)

    Das, Pc; Kandel, Ramesh; Sikka, Kapil; Dey, Ab

    2014-01-01

    Amphotericin-B, a broad spectrum antifungal agent, has been known to cause adverse effects such as nephrotoxicity and infusion-related side effects such as fever, chills, rigor, and arthralgias. However, ototoxicity as an adverse effect of Amphotericin-B has not yet been reported in medical literature. We here report a case of a reversible form of ototoxicity induced by liposomal Amphotericin-B (L-AmB).

  7. Assembly of Liposomes Controlled by Triple Helix Formation

    DEFF Research Database (Denmark)

    Vogel, Stefan; Jakobsen, Ulla

    2013-01-01

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

  8. Liposomal delivery of radionuclides for cancer diagnostics and radiotherapy

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa

    requirements governing quality assurance and considerations during development of a liposomal PET radiopharmaceutical for clinical use. In addition, the opportunity to use larger animals as clinical cancer patients for improving 64Culiposomes as PET imaging agents is briefly described followed by a short......Molecular imaging is increasingly being used as an integrated discipline in designing radiotherapeutic agents and diagnostic imaging agents, and in developing drugs in general. In recent years, the use of the radionuclide and positron emitter copper-64 (64Cu) has become increasingly important......, as the use of positron emission tomography (PET) scanners for molecular and diagnostic imaging has become more attractive. Furthermore, the importance of molecular and diagnostic imaging in nanotechnology has also been recognized, and significant research has been conducted on radiolabeled liposomes...

  9. Recurrent Candida albicans Ventriculitis Treated with Intraventricular Liposomal Amphotericin B

    Directory of Open Access Journals (Sweden)

    Demet Toprak

    2015-01-01

    Full Text Available Central nervous system (CNS infection with Candida is rare but significant because of its high morbidity and mortality. When present, it is commonly seen among immunocompromised and hospitalized patients. Herein, we describe a case of a four-year-old boy with acute lymphoblastic leukemia (ALL who experienced recurrent Candida albicans meningitis. The patient was treated successfully with intravenous liposomal amphotericin B at first attack, but 25 days after discharge he was readmitted to hospital with symptoms of meningitis. Candida albicans was grown in CFS culture again and cranial magnetic resonance imaging (MRI showed ventriculitis. We administered liposomal amphotericin B both intravenously and intraventricularly and favorable result was achieved without any adverse effects. Intraventricular amphotericin B may be considered for the treatment of recurrent CNS Candida infections in addition to intravenous administration.

  10. Development of Liposomal Ciprofloxacin to Treat Lung Infections

    Directory of Open Access Journals (Sweden)

    David Cipolla

    2016-03-01

    Full Text Available Except for management of Pseudomonas aeruginosa (PA in cystic fibrosis, there are no approved inhaled antibiotic treatments for any other diseases or for infections from other pathogenic microorganisms such as tuberculosis, non-tuberculous mycobacteria, fungal infections or potential inhaled biowarfare agents including Francisella tularensis, Yersinia pestis and Coxiella burnetii (which cause pneumonic tularemia, plague and Q fever, respectively. Delivery of an antibiotic formulation via the inhalation route has the potential to provide high concentrations at the site of infection with reduced systemic exposure to limit side effects. A liposomal formulation may improve tolerability, increase compliance by reducing the dosing frequency, and enhance penetration of biofilms and treatment of intracellular infections. Two liposomal ciprofloxacin formulations (Lipoquin® and Pulmaquin® that are in development by Aradigm Corporation are described here.

  11. Lateral Tension-Induced Penetration of Particles into a Liposome

    Directory of Open Access Journals (Sweden)

    Kazuki Shigyou

    2017-07-01

    Full Text Available It is important that we understand the mechanism of the penetration of particles into a living cell to achieve advances in bionanotechnology, such as for treatment, visualization within a cell, and genetic modification. Although there have been many studies on the application of functional particles to cells, the basic mechanism of penetration across a biological membrane is still poorly understood. Here we used a model membrane system to demonstrate that lateral membrane tension drives particle penetration across a lipid bilayer. After the application of osmotic pressure, fully wrapped particles on a liposome surface were found to enter the liposome. We discuss the mechanism of the tension-induced penetration in terms of narrow constriction of the membrane at the neck part. The present findings are expected to provide insight into the application of particles to biological systems.

  12. Astragalus Saponins and Liposome Constitute an Efficacious Adjuvant Formulation for Cancer Vaccines.

    Science.gov (United States)

    Zhang, Xiao-Ping; Li, Ying-Dong; Luo, Lu-Lu; Liu, Yong-Qi; Li, Yang; Guo, Chao; Li, Zhen-Dong; Xie, Xiao-Rong; Song, Hai-Xia; Yang, Li-Ping; Sun, Shao-Bo; An, Fang-Yu

    2018-02-01

    Cancer vaccines mostly aim to induce cytotoxic T lymphocytes (CTLs) against tumors. An appropriate adjuvant is of fundamental importance for inducing cellular immune response. Since the antigen in particulate form is substantially more immunogenic than soluble form antigen, it is beneficial to interact with antigen-presenting cells membrane to induce robust CD8 + T cell activation following vaccination. Based on previous research, we designed an adjuvant formulation by combining Astragalus saponins, cholesterol, and liposome to incorporate antigen into a particulate delivery system, so as to enhance cellular immune response. Meanwhile, angiogenesis contributes to tumor growth and metastasis, and basic fibroblast growth factor (bFGF) is involved in tumor angiogenesis. Therefore, using lipo-saponins adjuvant formulation and a human recombinant bFGF antigen protein, we tried to induce bFGF-specific CTL response to inhibit tumor angiogenesis to achieve antitumor activity. After five immunizations, the lipo-saponins/bFGF complex elicited robust antibody response and markedly higher amount of interferon-γ in BALB/c mice, resulting in superior antitumor activities. Decreased microvessel density in CD31 immunohistochemistry and the lysis of vascular endothelial cells by the T lymphocytes from the immunized mice indicated that the immunity inhibited the angiogenesis of tumors and further led to the inhibition of tumors. Our data suggest that the approach to construct adjuvant formulation between liposome and Astragalus saponins appeared highly desirable, and that Astragalus saponins may be utilized as a valuable additive for enhancing the effectiveness of vaccines and stimulating an appropriate immune response that can benefit tumor therapy.

  13. Design of peptide-targeted liposomes containing nucleic acids.

    Science.gov (United States)

    Santos, Adriana O; da Silva, Lígia C Gomes; Bimbo, Luís M; de Lima, Maria C Pedroso; Simões, Sérgio; Moreira, João N

    2010-03-01

    Anticancer systemic gene silencing therapy has been so far limited by the inexistence of adequate carrier systems that ultimately provide an efficient intracellular delivery into target tumor cells. In this respect, one promising strategy involves the covalent attachment of internalizing-targeting ligands at the extremity of PEG chains grafted onto liposomes. Therefore, the present work aims at designing targeted liposomes containing nucleic acids, with small size, high encapsulation efficiency and able to be actively internalized by SCLC cells, using a hexapeptide (antagonist G) as a targeting ligand. For this purpose, the effect of the liposomal preparation method, loading material (ODN versus siRNA) and peptide-coupling procedure (direct coupling versus post-insertion) on each of the above-mentioned parameters was assessed. Post-insertion of DSPE-PEG-antagonist G conjugates into preformed liposomes herein named as stabilized lipid particles, resulted in targeted vesicles with a mean size of about 130 nm, encapsulation efficiency close to 100%, and a loading capacity of approximately 5 nmol siRNA/mumol of total lipid. In addition, the developed targeted vesicles showed increased internalization in SCLC cells, as well as in other tumor cells and HMEC-1 microvascular endothelial cells. The improved cellular association, however, did not correlate with enhanced downregulation of the target protein (Bcl-2) in SCLC cells. These results indicate that additional improvements need to be performed in the future, namely by ameliorating the access of the nucleic acids to the cytoplasm of the tumor cells following receptor-mediated endocytosis. Copyright 2009 Elsevier B.V. All rights reserved.

  14. BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

    Czech Academy of Sciences Publication Activity Database

    Škorpilová, Ludmila; Rimpelová, S.; Jurášek, M.; Buděšínský, Miloš; Lokajová, Jana; Effenberg, R.; Slepička, P.; Ruml, T.; Kmoníčková, Eva; Drašar, P. B.; Wimmer, Zdeněk

    2017-01-01

    Roč. 13, JUL 4 (2017), s. 1316-1324 ISSN 1860-5397 R&D Projects: GA MŠk LD15012; GA MŠk(CZ) LO1304 Institutional support: RVO:61389030 ; RVO:61388963 ; RVO:68378041 Keywords : BODIPY conjugates * Cancer targeting * Drug delivery * Liposomes * Natural compounds * Sesquiterpene lactone trilobolide Subject RIV: CC - Organic Chemistry; FR - Pharmacology ; Medidal Chemistry (UEM-P) OBOR OECD: Organic chemistry; Pharmacology and pharmacy (UEM-P) Impact factor: 2.337, year: 2016

  15. Formation of drug nanocrystals under nanoconfinement afforded by liposomes

    DEFF Research Database (Denmark)

    Cipolla, D.; Wu, H.; Salentinig, Stefan

    2016-01-01

    Nanocrystals of drug substances have important therapeutic applications, but their preparation is often difficult due to size control in bottom up approaches, or energetic milling and surface activation in top down processing. In this study, confinement within liposome nanocompartments is demonst...... physical means (e.g., freeze/thaw) is an attractive possibility, especially in highly regulated industries such as pharmaceuticals where qualitative and quantitative changes of composition would require extensive safety evaluations....

  16. Liposome encapsulated albumin-paclitaxel nanoparticle for enhanced antitumor efficacy.

    Science.gov (United States)

    Ruttala, Hima Bindu; Ko, Young Tag

    2015-03-01

    Albumin nanoparticles have been explored as a promising delivery system for various therapeutic agents. One limitation of such formulations is their poor colloidal stability in vivo. Present study aimed at enhancing the chemotherapeutic potential of paclitaxel by improving the colloidal stability and pharmacokinetic properties of albumin-paclitaxel nanoparticles (APNs) such as Abraxane®. This was accomplished by encapsulating the preformed APNs into PEGylated liposomal bilayer by thin-film hydration/extrusion technique. The resulting liposome-encapsulated albumin-paclitaxel hybrid nanoparticles (L-APNs) were nanosized (~200 nm) with uniform spherical dimensions. The successful incorporation of albumin-paclitaxel nanoparticle (NP) in liposome was confirmed by size exclusion chromatography analysis. Such hybrid NP showed an excellent colloidal stability even at 100-fold dilutions, overcoming the critical drawback associated with simple albumin-paclitaxel NP system. L-APNs further showed higher cytotoxic activity towards B16F10 and MCF-7 cells than APN; this effect was characterized by arrest at the G2/M phase and a higher prevalence of apoptotic subG1 cells. Finally, pharmacokinetic and biodistribution studies in tumor mice demonstrated that L-APNs showed a significantly enhanced plasma half-life, and preferential accumulation in the tumor. Taken together, the data indicate that L-APNs can be promising therapeutic vehicles for enhanced delivery of PTX to tumor sites.

  17. In vivo hypertensive arterial wall uptake of radiolabeled liposomes

    International Nuclear Information System (INIS)

    Hodis, H.N.; Amartey, J.K.; Crawford, D.W.; Wickham, E.; Blankenhorn, D.H.

    1990-01-01

    Using five sham-operated and seven aortic coarctation-induced hypertensive New Zealand White rabbits intravenously injected with neutral small unilamellar vesicles loaded with [111In]nitrilotriacetic acid, we demonstrated in vivo that the normal aortic arterial wall participates in liposome uptake and that this uptake is increased in the hypertensive aortic wall by approximately threefold (p less than or equal to 0.0001). Among the three regions examined, aortic arch, thoracic aorta, and lower abdominal aorta, the difference in uptake between the normotensive and hypertensive arterial walls was significantly different, p less than or equal to 0.05, p less than or equal to 0.0001, and p less than 0.05, respectively. The uptake by the different regions of the hypertensive arterial wall is consistent with the pathological changes present in these areas. Furthermore, the extent of liposome uptake by the aortic wall is strongly correlated with the height of the blood pressure (r = 0.85, p = 0.001, n = 11). We conclude that neutral small unilamellar liposomes can be used to carry agents into the arterial wall in vivo in the study of hypertensive vascular disease and could be especially useful for the delivery of pharmacologically or biologically active agents that would otherwise be inactivated within the circulation or are impermeable to the arterial wall

  18. Experimental results of chemical recording using thermally sensitive liposomes

    Science.gov (United States)

    Tanner, Maria E.; Vasievich, Elizabeth A.; Protz, Jonathan M.

    2008-04-01

    A new generation of inertial measurement technology is being developed enabling a 10-micron particle to be "aware" of its geospatial location and respond to this information. The proposed approach combines an inertially-sensitive nano-structure or nano fluid/structure system with a nano-sized chemical reactor that functions as an analog computer. By using chemistry to perform the necessary computational steps in our device, it is possible to overcome traditional limitations on device size. The proposed nanodevice utilizes mechanical sensing and chemical recording to record the time history of various state variables. Using a micro-track containing regions of different temperatures and thermally-sensitive liposomes (TSL), a range of accelerations can be recorded and the position determined. Through careful design, TSL can be developed that have unique transition temperatures and each class of TSL will contain a unique DNA sequence that serves as an identifier. Acceleration can be detected through buoyancy-driven convection. As the liposomes travel to regions of warmer temperature, they will release their contents at the recording site, thus documenting the acceleration. This paper will present the initial proof-of-concept experimental results achieved from chemical recording of the state variable temperature. The experiment focuses on the liposome release of the DNA due to temperature variations and subsequent binding and recording of the time history. These results prove the feasibility of this method of sensing and recording of the history of state variables.

  19. Effect of microwave radiation on the biophysical properties of liposomes.

    Science.gov (United States)

    Gaber, Mohamed H; Abd El Halim, N; Khalil, W A

    2005-04-01

    Steadily growing use of electromagnetic fields, especially in conjunction with wireless communication systems, has led to increasing public concern about possible health effects of electromagnetic radiation. However, besides the well-known thermal effect of electromagnetic fields on biological tissue, there is no clear evidence of further athermal interaction mechanisms with biological systems. The present study was designed to determine the changes in bilayer permeability in egg lecithin multilamellar vesicles after exposure to 900 MHz microwave radiation for a period of 5 h. Specific absorption rate (SAR) of the radiation for the investigated liposome sample was found to be 12 +/- 1 W/kg. Liposomal changes in permeability were monitored using a light scattering technique. Optical anisotropy of the liposome sample decreased dramatically upon exposure to microwave radiation, indicating structural changes in acyl chain packing. IR and NMR ((1)H NMR) studies, which have been employed to reveal structural alterations in microwave, exposed vesicles showed an increased damage upon exposure to microwave. The changes observed in the (1)H NMR spectrum of the microwave exposed sample indicated hydrolysis of carboxylic and phosphoric esters. IR study showed conformational changes in the acyl chains of the lipids upon microwave exposure. However, both IR and (31)P NMR did not show any appreciable changes in the head group part of the lipids.

  20. A first step toward liposome-mediated intracellular bacteriophage therapy.

    Science.gov (United States)

    Nieth, Anita; Verseux, Cyprien; Barnert, Sabine; Süss, Regine; Römer, Winfried

    2015-01-01

    The emergence of antibiotic-resistant bacteria presents a severe challenge to medicine and public health. While bacteriophage therapy is a promising alternative to traditional antibiotics, the general inability of bacteriophages to penetrate eukaryotic cells limits their use against resistant bacteria, causing intracellular diseases like tuberculosis. Bacterial vectors show some promise in carrying therapeutic bacteriophages into cells, but also bring a number of risks like an overload of bacterial antigens or the acquisition of virulence genes from the pathogen. As a first step in the development of a non-bacterial vector for bacteriophage delivery into pathogen-infected cells, we attempted to encapsulate bacteriophages into liposomes. Here we report effective encapsulation of the model bacteriophage λeyfp and the mycobacteriophage TM4 into giant liposomes. Furthermore, we show that liposome-associated bacteriophages are taken up into eukaryotic cells more efficiently than free bacteriophages. These are important milestones in the development of an intracellular bacteriophage therapy that might be useful in the fight against multi-drug-resistant intracellular pathogens like Mycobacterium tuberculosis.

  1. Liposome-Based Delivery Systems in Plant Polysaccharides

    Directory of Open Access Journals (Sweden)

    Meiwan Chen

    2012-01-01

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

  2. Thermosensitive liposomes entrapping iron oxide nanoparticles for controllable drug release

    International Nuclear Information System (INIS)

    Tai, L-A; Wang, Y-C; Wang, Y-J; Yang, C-S; Tsai, P-J; Lo, L-W

    2009-01-01

    Iron oxide nanoparticles can serve as a heating source upon alternative magnetic field (AMF) exposure. Iron oxide nanoparticles can be mixed with thermosensitive nanovehicles for hyperthermia-induced drug release, yet such a design and mechanism may not be suitable for controllable drug release applications in which the tissues are susceptible to environmental temperature change such as brain tissue. In the present study, iron oxide nanoparticles were entrapped inside of thermosensitive liposomes for AMF-induced drug release while the environmental temperature was maintained at a constant level. Carboxyfluorescein was co-entrapped with the iron oxide nanoparticles in the liposomes as a model compound for monitoring drug release and environmental temperature was maintained with a water circulator jacket. These experiments have been successfully performed in solution, in phantom and in anesthetized animals. Furthermore, the thermosensitive liposomes were administered into rat forearm skeletal muscle, and the release of carboxylfluorescein triggered by the external alternative magnetic field was monitored by an implanted microdialysis perfusion probe with an on-line laser-induced fluorescence detector. In the future such a device could be applied to simultaneous magnetic resonance imaging and non-invasive drug release in temperature-sensitive applications.

  3. Liposomal Systems as Nanocarriers for the Antiviral Agent Ivermectin

    Directory of Open Access Journals (Sweden)

    Romina Croci

    2016-01-01

    Full Text Available RNA virus infections can lead to the onset of severe diseases such as fever with haemorrhage, multiorgan failure, and mortality. The emergence and reemergence of RNA viruses continue to pose a significant public health threat worldwide with particular attention to the increasing incidence of flaviviruses, among others Dengue, West Nile Virus, and Yellow Fever viruses. Development of new and potent antivirals is thus urgently needed. Ivermectin, an already known antihelminthic drug, has shown potent effects in vitro on Flavivirus helicase, with EC50 values in the subnanomolar range for Yellow Fever and submicromolar EC50 for Dengue Fever, Japanese encephalitis, and tick-borne encephalitis viruses. However ivermectin is hampered in its application by pharmacokinetic problems (little solubility and high cytotoxicity. To overcome such problems we engineered different compositions of liposomes as ivermectin carriers characterizing and testing them on several cell lines for cytotoxicity. The engineered liposomes were less cytotoxic than ivermectin alone and they showed a significant increase of the antiviral activity in all the Dengue stains tested (1, 2, and S221. In the current study ivermectin is confirmed to be an effective potential antiviral and liposomes, as drug carriers, are shown to modulate the drug activity. All together the results represent a promising starting point for future improvement of ivermectin as antiviral and its delivery.

  4. Integration of β-carotene molecules in small liposomes

    International Nuclear Information System (INIS)

    Andreeva, Atanaska; Popova, Antoaneta

    2010-01-01

    The most typical feature of carotenoids is the long polyene chain with conjugated double bonds suggesting that they can serve as conductors of electrons, acting as 'molecular wires', important elements in the molecular electronic devices. Carotenoids are essential components of photosynthetic systems, performing different functions as light harvesting, photoprotection and electron transfer. They act also as natural antioxidants. In addition they perform structural role stabilizing the three-dimensional organization of photosynthetic membranes. Carotenoids contribute to the stability of the lipid phase, preserving the membrane integrity under potentially harmful environmental conditions. Carotenoids can be easily integrated into model membranes, facilitating the investigation of their functional roles. In carotenoid-egg phosphatidylcholine (EPC) liposomes ss-carotene is randomly distributed in the hydrocarbon interior of the bilayer, without any preferred, well defined orientation and retains a substantial degree of mobility. Here we investigate the degree of integration of ss-carotene in small unilamellar EPC liposomes and the changes in ss-carotene absorption and Raman spectra due to the lipid-pigment interaction. All observed changes in ss-carotene absorption and Raman spectra may be regarded as a result of the lipid-pigment interactions leading to the polyene geometry distortion and increasing of the environment heterogenety in the liposomes as compared to the solutions.

  5. Ciprofloxacin in polyethylene glycol-coated liposomes: efficacy in rat models of acute or chronic Pseudomonas aeruginosa infection

    NARCIS (Netherlands)

    I.A.J.M. Bakker-Woudenberg (Irma); M.T. ten Kate (Marian); L. Guo; P. Working; J.W. Mouton (Johan)

    2002-01-01

    textabstractIn a previous study in experimental Klebsiella pneumoniae pneumonia, the therapeutic potential of ciprofloxacin was significantly improved by encapsulation in polyethylene glycol-coated ("pegylated") long-circulating (STEALTH) liposomes. Pegylated liposomal

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

    Science.gov (United States)

    Yang, Zhiwen; Yu, Songlin; Fu, Dahua

    2010-02-01

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

  7. Periarticular Injection of Liposomal Bupivacaine Offers No Benefit Over Standard Bupivacaine in Total Knee Arthroplasty: A Prospective, Randomized, Controlled Trial.

    Science.gov (United States)

    Alijanipour, Pouya; Tan, Timothy L; Matthews, Christopher N; Viola, Jessica R; Purtill, James J; Rothman, Richard H; Parvizi, Javad; Austin, Matthew S

    2017-02-01

    Periarticular injection of liposomal bupivacaine has been adopted as part of multimodal pain management after total knee arthroplasty (TKA). In this prospective, randomized clinical trial, we enrolled 162 patients undergoing primary TKA in a single institution between January 2014 and May 2015. Eighty-seven patients were randomized to liposomal bupivacaine (experimental group), and 75 patients were randomized to free bupivacaine (control group). All patients received spinal anesthesia and otherwise identical surgical approaches, pain management, and rehabilitation protocols. Outcomes evaluated include the patient-reported visual analog pain scores, narcotic consumption, and narcotic-related side effects (Brief Pain Inventory) within 96 hours after surgery as well as functional outcomes using the Knee Society Score and the Short-Form 12 measured preoperatively and at 4-6 weeks after surgery. There were no statistically significant differences between the groups in terms of postoperative daily pain scores, narcotic consumption (by-day and overall), or narcotic-related side effects. There were no statistically significant differences between the groups in terms of surgical (P = .76) and medical complications or length of hospital stay (P = .35). There were no statistically significant differences in satisfaction between the groups (P = .56) or between the groups in postoperative Knee Society Score (P = .53) and the Short-Form 12 at 4-6 weeks (P = .82, P = .66). As part of multimodal pain management protocol, periarticular injection of liposomal bupivacaine compared with bupivacaine HCl did not result in any clinically or statistically significant improvement of the measured outcomes following TKA. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Borborema, Samanta Etel Treiger

    2010-01-01

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

  9. A case of spontaneous ventriculocisternostomy

    International Nuclear Information System (INIS)

    Yamane, Kanji; Yoshimoto, Hisanori; Harada, Kiyoshi; Uozumi, Tohru; Kuwabara, Satoshi.

    1983-01-01

    The authors experienced a case of spontaneous ventriculocisternostomy diagnosed by CT scan with metrizamide and Conray. Patient was 23-year-old male who had been in good health until one month before admission, when he began to have headache and tinnitus. He noticed bilateral visual acuity was decreased about one week before admission and vomiting appeared two days before admission. He was admitted to our hospital because of bilateral papilledema and remarkable hydrocephalus diagnosed by CT scan. On admission, no abnormal neurological signs except for bilateral papilledema were noted. Immediately, right ventricular drainage was performed. Pressure of the ventricle was over 300mmH 2 O and CSF was clear. PVG and PEG disclosed an another cavity behind the third ventricle, which was communicated with the third ventricle, and occlusion of aqueduct of Sylvius. Metrizamide CT scan and Conray CT scan showed a communication between this cavity and quadrigeminal and supracerebellar cisterns. On these neuroradiological findings, the diagnosis of obstructive hydrocephalus due to benign aqueduct stenosis accompanied with spontaneous ventriculocisternostomy was obtained. Spontaneous ventriculocisternostomy was noticed to produce arrest of hydrocephalus, but with our case, spontaneous regression of such symptoms did not appeared. By surgical ventriculocisternostomy (method by Torkildsen, Dandy, or Scarff), arrest of hydrocephalus was seen in about 50 to 70 per cent, which was the same results as those of spontaneous ventriculocisternostomy. It is concluded that VP shunt or VA shunt is thought to be better treatment of obstructive hydrocephalus than the various kinds of surgical ventriculocisternostomy. (J.P.N.)

  10. Optical antenna enhanced spontaneous emission.

    Science.gov (United States)

    Eggleston, Michael S; Messer, Kevin; Zhang, Liming; Yablonovitch, Eli; Wu, Ming C

    2015-02-10

    Atoms and molecules are too small to act as efficient antennas for their own emission wavelengths. By providing an external optical antenna, the balance can be shifted; spontaneous emission could become faster than stimulated emission, which is handicapped by practically achievable pump intensities. In our experiments, InGaAsP nanorods emitting at ∼ 200 THz optical frequency show a spontaneous emission intensity enhancement of 35 × corresponding to a spontaneous emission rate speedup ∼ 115 ×, for antenna gap spacing, d = 40 nm. Classical antenna theory predicts ∼ 2,500 × spontaneous emission speedup at d ∼ 10 nm, proportional to 1/d(2). Unfortunately, at d antenna efficiency drops below 50%, owing to optical spreading resistance, exacerbated by the anomalous skin effect (electron surface collisions). Quantum dipole oscillations in the emitter excited state produce an optical ac equivalent circuit current, I(o) = qω|x(o)|/d, feeding the antenna-enhanced spontaneous emission, where q|x(o)| is the dipole matrix element. Despite the quantum-mechanical origin of the drive current, antenna theory makes no reference to the Purcell effect nor to local density of states models. Moreover, plasmonic effects are minor at 200 THz, producing only a small shift of antenna resonance frequency.

  11. Liposomal clodronate selectively eliminates microglia from primary astrocyte cultures

    Directory of Open Access Journals (Sweden)

    Kumamaru Hiromi

    2012-05-01

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

  12. Tumor burden talks in cancer treatment with PEGylated liposomal drugs.

    Directory of Open Access Journals (Sweden)

    Yi-Yu Lin

    Full Text Available PURPOSE: PEGylated liposomes are important drug carriers that can passively target tumor by enhanced permeability and retention (EPR effect in neoplasm lesions. This study demonstrated that tumor burden determines the tumor uptake, and also the tumor response, in cancer treatment with PEGylated liposomal drugs in a C26/tk-luc colon carcinoma-bearing mouse model. METHODS: Empty PEGylated liposomes (NanoX and those encapsulated with VNB (NanoVNB were labeled with In-111 to obtain InNanoX and InVNBL in high labeling yield and radiochemical purity (all >90%. BALB/c mice bearing either small (58.4±8.0 mm(3 or large (102.4±22.0 mm(3 C26/tk-luc tumors in the right dorsal flank were intravenously administered with NanoVNB, InNanoX, InVNBL, or NanoX as a control, every 7 days for 3 times. The therapeutic efficacy was evaluated by body weight loss, tumor growth inhibition (using calipers and bioluminescence imaging and survival fraction. The scintigraphic imaging of tumor mouse was performed during and after treatment. RESULTS: The biodistribution study of InVNBL revealed a clear inverse correlation (r (2 = 0.9336 between the tumor uptake and the tumor mass ranged from 27.6 to 623.9 mg. All three liposomal drugs showed better therapeutic efficacy in small-tumor mice than in large-tumor mice. Tumor-bearing mice treated with InVNBL (a combination drug showed the highest tumor growth inhibition rate and survival fraction compared to those treated with NanoVNB (chemodrug only and InNanoX (radionuclide only. Specific tumor targeting and significantly increased tumor uptake after periodical treatment with InVNBL were evidenced by scintigraphic imaging, especially in mice bearing small tumors. CONCLUSION: The significant differences in the outcomes of cancer treatment and molecular imaging between animals bearing small and large tumors revealed that tumor burden is a critical and discriminative factor in cancer therapy using PEGylated liposomal drugs.

  13. Liposomal drug delivery system from laboratory to clinic

    Directory of Open Access Journals (Sweden)

    Kshirsagar N

    2005-01-01

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

  14. The role of surface charge density in cationic liposome-promoted dendritic cell maturation and vaccine-induced immune responses

    Science.gov (United States)

    Ma, Yifan; Zhuang, Yan; Xie, Xiaofang; Wang, Ce; Wang, Fei; Zhou, Dongmei; Zeng, Jianqiang; Cai, Lintao

    2011-05-01

    Cationic liposomes have emerged as a novel adjuvant and antigen delivery system to enhance vaccine efficacy. However, the role of surface charge density in cationic liposome-regulated immune responses has not yet been elucidated. In the present study, we prepared a series of DOTAP/DOPC cationic liposomes with different surface densities by incorporating varying amounts of DOPC (a neutral lipid) into DOTAP (a cationic lipid). The results showed that DOTAP/DOPC cationic liposome-regulated immune responses relied on the surface charge density, and might occur through ROS signaling. The liposomes with a relatively high charge density, such as DOTAP/DOPC 5 : 0 and 4 : 1 liposomes, potently enhanced dendritic cell maturation, ROS generaion, antigen uptake, as well as the production of OVA-specific IgG2a and IFN-γ. In contrast, low-charge liposomes, such as DOTAP/DOPC 1 : 4 liposome, failed to promote immune responses even at high concentrations, confirming that the immunoregulatory effect of cationic liposomes is mostly attributable to their surface charge density. Moreover, the DOTAP/DOPC 1 : 4 liposome suppressed anti-OVA antibody responses in vivo. Overall, maintaining an appropriate surface charge is crucial for optimizing the adjuvant effect of cationic liposomes and enhancing the efficacy of liposome-based vaccines.

  15. In vivo Evaluation of PEGylated 64Cu-liposomes with Theranostic and Radiotherapeutic Potential using Micro PET/CT

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa; Henriksen, Jonas Rosager; Binderup, Tina

    2016-01-01

    both 64Cu and 177Lu radionuclides with PEGylated liposomes,and essentially no leakage of the encapsulated radionuclidewas observed upon storage and after serum incubationfor 24 h at 37 °C. The 10 mol% PEG liposomes showedhigher tumor accumulation (6.2±0.2 %ID/g) than the 5mol% PEG liposomes...

  16. Spontaneous subcapsular and perirrenal hemorrhage

    International Nuclear Information System (INIS)

    Fuster, M.J.; Saez, J.; Perez-Paya, F.J.; Fernandez, F.

    1997-01-01

    To assess the role of CT in the etiologic diagnosis of spontaneous subcapsular and perirrenal hemorrhage. The CT findings are described in 13 patients presenting subcapsular and perirrenal hemorrhage. Those patients in whom the bleeding was not spontaneous were excluded. Surgical confirmation was obtained in nine cases. In 11 of the 13 cases (84.6%), involving five adenocarcinomas, five angiomyolipoma, two complicated cysts and one case of panarterities nodosa, CT disclosed the underlying pathology. In two cases (15.4%), it only revealed the extension of the hematoma, but gave no clue to its origin. CT is the technique of choice when spontaneous subcapsular and perirrenal hemorrhage is suspected since, in most cases, it reveals the underlying pathology. (Author)

  17. Spontaneous isolated celiac artery dissection

    Directory of Open Access Journals (Sweden)

    Tuba Cimilli Ozturk

    2011-01-01

    Full Text Available Dyspepsia with mild, stabbing epigastric discomfort without history of trauma is a very common symptom that emergency physicians see in their daily practice. Vascular emergencies, mostly the aortic dissection and aneurysm, are always described in the differential diagnosis with persistent symptoms. Isolated celiac artery dissection occurring spontaneously is a very rare diagnosis. The involvement of branch vessels is generally observed and patients show various clinical signs and symptoms according to the involved branch vessel. Here we are presenting a case with spontaneous isolated celiac artery dissection, without any branch vessel involvement or visceral damage, detected by computed tomography scans taken on admission.

  18. Spontaneous waves in muscle fibres

    Energy Technology Data Exchange (ETDEWEB)

    Guenther, Stefan; Kruse, Karsten [Department of Theoretical Physics, Saarland University, 66041 Saarbruecken (Germany); Max Planck Institute for the Physics of Complex Systems, Noethnitzer Street 38, 01187 Dresden (Germany)

    2007-11-15

    Mechanical oscillations are important for many cellular processes, e.g. the beating of cilia and flagella or the sensation of sound by hair cells. These dynamic states originate from spontaneous oscillations of molecular motors. A particularly clear example of such oscillations has been observed in muscle fibers under non-physiological conditions. In that case, motor oscillations lead to contraction waves along the fiber. By a macroscopic analysis of muscle fiber dynamics we find that the spontaneous waves involve non-hydrodynamic modes. A simple microscopic model of sarcomere dynamics highlights mechanical aspects of the motor dynamics and fits with the experimental observations.

  19. Synthesis of phthalocyanine conjugates with gold nanoparticles and liposomes for photodynamic therapy

    CSIR Research Space (South Africa)

    Nombona, N

    2012-02-01

    Full Text Available gold nanoparticles or encapsulated in liposomes. Cell viability studies showed the optimum phototoxic effect on non-malignant cells to be 4.5 J cm-2. The PDT effect of the liposome bound phthalocyanine showed extensive damage of the breast cancer cells...

  20. Inhibition of the Growth of Plasmodium falciparum in Culture by Stearylamine-Phosphatidylcholine Liposomes

    Directory of Open Access Journals (Sweden)

    Gulam Mustafa Hasan

    2011-01-01

    Full Text Available We have examined the effect of stearylamine (SA in liposomes on the viability of Plasmodium falciparum in culture by studying the inhibition of incorporation of [3H]-hypoxanthine in the nucleic acid of parasites. Stearylamine in liposomes significantly inhibits the growth of the parasites depending on the phospholipids composition. The maximum inhibition was observed when SA was delivered through Soya phosphatidylcholine (SPC liposomes. The chain length of alkyl group and density of SA in liposomes play a significant role in inhibiting the growth of the parasites. Incorporation of either cholesterol or Distearylphosphatidylethanolamine−Methoxy-Polyethylene glycol-2000 (DSPE-mPEG-2000 in Soya phosphatidylcholine-stearylamine (SPC-SA liposomes improves the efficacy. Intraerythrocytic entry of intact SPC-SA liposomes into infected erythrocytes was visualized using fluorescent microscopy. No hemolysis was observed in uninfected erythrocytes, and slight hemolysis was noted in infected erythrocytes at high concentrations of SPC-SA liposomes. Overall, our data suggested SA in SPC-liposomes might have potential application in malaria chemotherapy.

  1. The action of pimaricin, etruscomycin and amphotericin B on liposomes with varying sterol content

    NARCIS (Netherlands)

    Teerlink, T.; Kruijff, B. de; Demel, R.A.

    1980-01-01

    1. 1. The effect of pimaricin, etruscomycin and amphotericin B on the K+ release from liposomes is strongly dependent on their sterol concentration.Pimaricin and etruscomycin induce K+ release from egg lecithin liposomes with cholesterol contents of more than 25 and 10 mol%, respectively, at polyene

  2. [Separate factors influencing the interaction of carbohydrate- containing liposomes with galactose-specific lectins].

    Science.gov (United States)

    Dvorkin, V M; Vidershaĭn, G Ia

    1984-11-01

    Some natural (Gal-Cer, Lac-Cer, desyalylated gangliosides) and synthetic (HMGal) glycolipids differing in the length of the bridge linking the terminal galactose with the hydrophobic moiety were incorporated into the liposome membranes. The precipitation of the thus obtained vesicles induced by galactose-specific lectin RCA was studied. It was shown that when the amount of the glycolipids used for the incorporation into the liposomes (1 mol. %) was the same, the vesicles with HMGal or Gal-Cer incorporated into them did not precipitate in the presence of lectin, whereas the liposomes with incorporated Lac-Cer or desyalylated gangliosides did precipitate. It was thus concluded that in order for galactose-containing liposomes precipitation by lectin RCA1 to be induced, galactose should be separated from the liposome membrane with a distance not less than 7 A. The nature of lectin-induced nonspecific precipitation of ganglioside-containing liposomes, ganglioside mycelles and cardiolipin-lecithine liposomes containing lactosylceramide was investigated. Some nonspecific ionic interactions of negatively charged liposomes and ganglioside mycelles with lectin were observed, which disappeared with a rise in the NaCl concentration up to 150-200 mM.

  3. The modulation of physicochemical characterization of innovative liposomal platforms: the role of the grafted thermoresponsive polymers.

    Science.gov (United States)

    Chountoulesi, Maria; Kyrili, Aimilia; Pippa, Natassa; Meristoudi, Anastasia; Pispas, Stergios; Demetzos, Costas

    2017-05-01

    This study is focused on chimeric advanced drug delivery systems and specifically on thermosensitive liposomes, combining lipids and thermoresponsive polymers. In this investigation, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) chimeric liposomal systems were prepared, incorporating the homopolymer C 12 H 25 -poly(N-isopropylacrylamide)-COOH (C 12 H 25 -PNIPAM-COOH) and the block copolymer poly(n-butylacrylate-b-N-isoropylacrylamide) (PnBA-PNIPAM), at six different molar ratios. Both of these polymers contain the thermoresponsive PNIPAM block, which exhibits lower critical solution temperature (LCST) at 32 °C in aqueous solutions, changing its nature from hydrophilic to hydrophobic above LCST. During the preparation of liposomes, the dispersions were observed visually, while after the preparation we studied the alterations of the physicochemical characteristics, by measuring the size, size distribution and ζ-potential of prepared liposomes. The presence of polymer, either C 12 H 25 -PNIPAM-COOH or PnBA-PNIPAM, resulted in liposomes exhibiting different physicochemical characteristics in comparison to conventional DPPC liposomes. At the highest percentage of the polymeric guest, chimeric liposomes were found to retain their size during the stability studies. The incorporation of the appropriate amount of these novel thermoresponsive polymers yields liposomal stabilization and imparts thermoresponsiveness, due to the functional PNIPAM block.

  4. On the interaction of fluorophore-encapsulating PEGylated lecithin liposomes with hamster and human platelets

    NARCIS (Netherlands)

    Heger, M.; Salles, I.I.; van Vuure, W.; Deckmyn, H.; Beek, J.F.

    2009-01-01

    Polyethylene glycol (PEG)-grafted phosphatidylcholine liposomes are used as drug carriers due to their low immunogenicity and prolonged circulation time. The interaction between sterically stabilized lecithin liposomes and platelets has not been investigated before, and deserves to be subjected to

  5. CHEMOIMMUNOTHERAPY OF MURINE LIVER METASTASES WITH 5-FLUOROURACIL IN COMBINATION WITH LIPOSOME-ENCAPSULATED MURAMYL DIPEPTIDE

    NARCIS (Netherlands)

    DAEMEN, T; DONTJE, BHJ; REGTS, J; SCHERPHOF, GL

    The therapeutic effect of a combination of liposomal muramyl dipeptide (MDP) and 5-fluorouracil (5FU) was studied in a murine tumor model of hepatic metastases of the tumor cell line C26, a colon adenocarcinoma. Liposomal MDP (250 mug/kg body wt) and a low, nontoxic, dose of 5FU (10 mg/kg body wt)

  6. Liposome accumulation in irradiated tumors display important tumor and dose dependent differences

    DEFF Research Database (Denmark)

    Hansen, Anders Elias; Fliedner, Frederikke Petrine; Henriksen, Jonas Rosager

    2018-01-01

    Radiation therapy may affect several important parameters in the tumor microenvironment and thereby influence the accumulation of liposomes by the enhanced permeability and retention (EPR)-effect. Here we investigate the effect of single dose radiation therapy on liposome tumor accumulation by PE...

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

    Science.gov (United States)

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

    2016-04-05

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

  8. Improved Efficacy of Liposomal Doxorubicin Treatment of Superficial Tumors by Thermotherapy.

    Science.gov (United States)

    Ping, Xiong; Angang, Ding; Xia, Gong; Yinzhu, Zhao; Jia, Li; Guofeng, Shen; Yazhu, Chen

    2016-04-01

    Our study aimed to investigate the effect of ultrasonic thermotherapy on the targeted delivery of liposomal doxorubicin to superficial tumors, local drug concentrations in tumor tissue, and the curative effect of chemotherapy. Twenty rabbits with VX2 tumors transplanted into the superficial muscle of the hind limb were randomly assigned to the following 4 treatment groups: (1) free doxorubicin, (2) liposomal doxorubicin hydrochloride, (3) liposomal doxorubicin hydrochloride plus 41 °C thermotherapy, and (4) liposomal doxorubicin hydrochloride plus 43 °C thermotherapy. Ultrasonic thermotherapy was delivered at 41 °C to 43 °C. Plasma, tumor, and organ/tissue homogenates were analyzed by high-pressure liquid chromatography to determine doxorubicin concentrations. The drug concentration in plasma and tumor tissue was significantly higher in the liposomal doxorubicin hydrochloride plus thermotherapy group than in the liposomal doxorubicin hydrochloride and free doxorubicin groups, but there were no significant differences among the 4 groups in the concentration in heart or kidney tissue. Combining thermotherapy with liposomal doxorubicin hydrochloride chemotherapy significantly increased the concentration of the drug in tumor tissue. The doxorubicin concentration was significantly higher in the liposomal doxorubicin hydrochloride plus 41 °C thermotherapy group. © The Author(s) 2015.

  9. Spatially Resolved Two-Color Diffusion Measurements in Human Skin Applied to Transdermal Liposome Penetration

    DEFF Research Database (Denmark)

    Brewer, Jonathan; Bloksgaard, Maria; Kubiak, Jakub

    2013-01-01

    and a hydrophilic fluorophore encapsulated in the liposome lumen-was measured using cross-correlation RICS. This type of experiment allows discrimination between separate (uncorrelated) and joint (correlated) diffusion of the two different fluorescent probes, giving information about liposome integrity. Independent...

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

    Science.gov (United States)

    Toyota, Hiroyasu; Asai, Tomohiro; Oku, Naoto

    2017-05-01

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

  11. Highly penetrative liposome nanomedicine generated by a biomimetic strategy for enhanced cancer chemotherapy.

    Science.gov (United States)

    Jia, Yali; Sheng, Zonghai; Hu, Dehong; Yan, Fei; Zhu, Mingting; Gao, Guanhui; Wang, Pan; Liu, Xin; Wang, Xiaobing; Zheng, Hairong

    2018-04-25

    Liposome nanomedicine has been successfully applied for cancer chemotherapy in patients. However, in general, the therapeutic efficacy is confined by its limited accumulation and penetration in solid tumors. Here, we established a biomimetic strategy for the preparation of highly penetrative liposome nanomedicine for enhanced chemotherapeutic efficacy. By applying this unique type of nanomedicine, membrane proteins on the cancer cells are used as highly penetrative targeting ligands. Biomimetic liposomes are highly stable, exhibiting a superior in vitro homologous targeting ability, and a 2.25-fold deeper penetration in 3D tumor spheroids when compared to conventional liposome nanomedicine. The fluorescence/photoacoustic dual-modal imaging approach demonstrated enhanced tumor accumulation and improved tumor penetration of the biomimetic liposome in C6 glioma tumor-bearing nude mice. Following the intravenous administration of biomimetic liposome nanomedicine, the tumor inhibition rate reached up to 93.3%, which was significantly higher when compared to that of conventional liposome nanomedicine (69.3%). Moreover, histopathological analyses demonstrated that biomimetic liposome nanomedicine has limited side effects. Therefore, these results suggested that a cancer cell membrane-based biomimetic strategy may provide a breakthrough approach for enhancing drug penetration and improving treatment efficacy, holding a great promise for further clinical studies.

  12. Selective partitioning of cholesterol and a model drug into liposomes of varying size

    DEFF Research Database (Denmark)

    Decker, Christiane; Fahr, Alfred; Kuntsche, Judith

    2012-01-01

    The resistance of a lipid bilayer with respect to a bending deformation generally depends on the presence of membrane additives such as sterols, cosurfactants, peptides, and drugs. As a consequence, the partitioning of membrane additives into liposomes becomes selective with respect to liposome s...

  13. Noninvasive control of the transport function of fluorescent coloured liposomal nanoparticles

    Science.gov (United States)

    Stelmashchuk, O.; Zherebtsov, E.; Zherebtsova, A.; Kuznetsova, E.; Vinokurov, A.; Dunaev, A.; Mamoshin, A.; Snimshchikova, I.; Borsukov, A.; Bykov, A.; Meglinski, I.

    2017-06-01

    The use of liposomal nanoparticles with an incorporated active substance is an innovative and promising approach to diagnostics and therapy. The application of liposomal nanoparticle-based drugs allows for targeted localized delivery, overcomes the natural barriers within the body effectively, and minimizes possible side effects. Liposomes are able to contain a variety of ingredients with practically no limitations to their chemical composition, chemical properties, or size of constituent molecules. This study evaluated the ability to control the passage of fluorescent dye-filled liposomes through the intestinal mucosal barrier after oral administration. For this purpose, the increase in transcutaneous registered fluorescence from tetrabromofluorescein dye was recorded and analysed. Fluorescence intensity was measured at the proximal end of the tail of an animal model after oral administration of the liposomes. Measurements were taken at the excitation wavelengths of 365 and 450 nm. The fluorescence intensity in the group treated with the fluorescent contrast agent encapsulated in liposomal particles increased 140% of the initial level, but in the group treated with pure contrast agent, the increase in detected fluorescence intensity did not exceed 110%. Mice that received empty liposomes as well as the control group did not demonstrate statistically significant changes in fluorescence intensity. A potential application of our results is an express laser optical method of monitoring the transport of orally administered liposomal particles. The results can be used to help create new optical tools for use in the development of new drugs and in high-throughput screening used during their testing.

  14. Protein-liposome conjugates using cysteine-lipids and native chemical ligation

    NARCIS (Netherlands)

    Reulen, Sanne W. A.; Brusselaars, Wilco W. T.; Langereis, Sander; Mulder, Willem J. M.; Breurken, Monica; Merkx, Maarten

    2007-01-01

    Liposomes have become popular drug delivery vehicles and have more recently also been applied as contrast agents for molecular imaging. Most current methods for functionalization of liposomes with targeting proteins rely on reactions of amine or thiol groups at the protein exterior, which generally

  15. Fast and efficient detection of tuberculosis antigens using liposome encapsulated secretory proteins of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Dileep Tiwari

    2017-04-01

    Conclusion: Our study demonstrated that the newly developed liposome tuberculosis antigen card test detected antigens in our study population with approximately 97.48% sensitivity and 95.79% specificity. This is the first study to report the liposomal encapsulation of culture filtrate proteins from M. tuberculosis for diagnostic application.

  16. The impact of metal complex lipids on viscosity and curvature of hybrid liposomes.

    Science.gov (United States)

    Ohtani, Ryo; Tokita, Tsukasa; Takaya, Tomohisa; Iwata, Koichi; Kinoshita, Masanao; Matsumori, Nobuaki; Nakamura, Masaaki; Lindoy, Leonard F; Hayami, Shinya

    2017-12-12

    A morphology transformation of hybrid liposomes was shown to occur from spherical vesicles to tubular micelles when increasing the ratio of the metal complex lipid present. Phase transition temperatures increased while viscosities decreased, indicating that the hybrids exhibit stronger interaction between heads but weaker interaction between alkyl chains than occurs in pristine liposomes.

  17. Enhanced efficacy of sublingual immunotherapy by liposome-mediated delivery of allergen

    DEFF Research Database (Denmark)

    Aliu, Have; Rask, Carola; Brimnes, Jens

    2017-01-01

    model. We investigated the liposome carriers' ability to improve tolerance induction of antigens compared to the - corresponding dose of free OVA. Mice were treated sublingually over 2 weeks with free or liposome encapsulated OVA followed by intraperitoneal injections and intranasal challenge. Mice...

  18. Liposome-binding assays to assess specificity and affinity of phospholipid-protein interactions

    NARCIS (Netherlands)

    Julkowska, M.M.; Rankenberg, J.M.; Testerink, C.

    2013-01-01

    Protein-lipid interactions play an important role in cellular protein relocation, activation and signal transduction. The liposome-binding assay is a simple and inexpensive method to examine protein-lipid binding in vitro. The phospholipids used for liposome production are dried and hydrated.

  19. Modulating spontaneous brain activity using repetitive transcranial magnetic stimulation

    NARCIS (Netherlands)

    van der Werf, Y.D.; Sanz-Arigita, E.J.; Menning, S.; van den Heuvel, O.A.

    2010-01-01

    Background: When no specific stimulus or task is presented, spontaneous fluctuations in brain activity occur. Brain regions showing such coherent fluctuations are thought to form organized networks known as 'resting-state' networks, a main representation of which is the default mode network.

  20. Spontaneous breakdown of PT symmetry in the complex Coulomb ...

    Indian Academy of Sciences (India)

    P T symmetry is spontaneously broken, however, for complex values of the form L = − 1 2 + i . In this case the potential remains P T -symmetric, while the two independent solutions are transformed to each other by the P T operation and at the same time, the two series of discrete energy eigenvalues turn into each ...