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Sample records for corneum lipids liposomes

  1. Stratum corneum lipid liposome-encapsulated panomycocin: preparation, characterization, and the determination of antimycotic efficacy against Candida spp. isolated from patients with vulvovaginitis in an in vitro human vaginal epithelium tissue model.

    Science.gov (United States)

    İzgü, Fatih; Bayram, Günce; Tosun, Kübra; İzgü, Demet

    2017-01-01

    In this study, a liposomal lyophilized powder formulation of panomycocin was developed for therapeutic purposes against vulvovaginal candidiasis which affects 80% of women worldwide. Panomycocin is a potent antimycotic protein secreted by the yeast Wickerhamomyces anomalus NCYC 434. This study involved the preparation of panomycocin-loaded stratum corneum lipid liposomes (SCLLs), characterization of the SCLLs, and determination of antimycotic efficacy of the formulation against Candida albicans and Candida glabrata clinical vaginal isolates in a human vaginal epithelium tissue model. The encapsulation and loading efficiencies of SCLLs were 73% and 76.8%, respectively. In transmission electron microscopy images, the SCLLs appeared in the submicron size range. Dynamic light scattering analyses showed that the SCLLs had uniform size distribution. Zeta potential measurements revealed stable and positively charged SCLLs. In Fourier transform infrared spectroscopy analyses, no irreversible interactions between the encapsulated panomycocin and the SCLLs were detected. The SCLLs retained >98% of encapsulated panomycocin in aqueous solution up to 12 hours. The formulation was fungicidal at the same minimum fungicidal concentration values for non-formulated pure panomycocin when tested on an in vitro model of vaginal candidiasis. This is the first study in which SCLLs and a protein as an active ingredient have been utilized together in a formulation. The results obtained in this study led us to conduct further preclinical trials of this formulation for the development of an effective topical anti-candidal drug with improved safety.

  2. Stratum Corneum Barrier Lipids in Cholesteatoma

    DEFF Research Database (Denmark)

    Svane-Knudsen, V; Halkier-Sørensen, L; Rasmussen, G

    2000-01-01

    emerged. When the corneocyte reaches the transitional stage to the stratum corneum, the Odland bodies accumulate near the cell membrane and discharge their contents of lipid and enzymes. The lipids are reorganized into multiple long sheets of lamellar structures that embrace the keratinized corneocytes......, as seen in the formation and maintenance of the cutaneous permeability barrier. In this study we draw the attention to the facts that the cholesteatoma epithelium is capable of producing not only cholesterol, but also several lipids, and that the lipid molecules are organized in multilamellar structures......Specimens from primary cholesteatomas were examined under the electron microscope using a lipid-retaining method that is best suited for intracellular lipids and a method that is best for intercellular lipids. In the stratum granulosum of the squamous epithelium, a large number of Odland bodies...

  3. Direct visualization of lipid domains in human skin stratum corneum's lipid membranes

    DEFF Research Database (Denmark)

    Plasencia, I; Norlen, Lars; Bagatolli, Luis

    2007-01-01

    scanning calorimetry, fluorescence spectroscopy, and two-photon excitation and laser scanning confocal fluorescence microscopy. Here we show that hydrated bilayers of human skin stratum corneum lipids express a giant sponge-like morphology with dimensions corresponding to the global three......-dimensional morphology of the stratum corneum extracellular space. These structures can be directly visualized using the aforementioned fluorescence microscopy techniques. At skin physiological temperatures (28 degrees C-32 degrees C), the phase state of these hydrated bilayers correspond microscopically (radial...

  4. Interactions of inertial cavitation bubbles with stratum corneum lipid bilayers during low-frequency sonophoresis.

    Science.gov (United States)

    Tezel, Ahmet; Mitragotri, Samir

    2003-12-01

    Interactions of acoustic cavitation bubbles with biological tissues play an important role in biomedical applications of ultrasound. Acoustic cavitation plays a particularly important role in enhancing transdermal transport of macromolecules, thereby offering a noninvasive mode of drug delivery (sonophoresis). Ultrasound-enhanced transdermal transport is mediated by inertial cavitation, where collapses of cavitation bubbles microscopically disrupt the lipid bilayers of the stratum corneum. In this study, we describe a theoretical analysis of the interactions of cavitation bubbles with the stratum corneum lipid bilayers. Three modes of bubble-stratum corneum interactions including shock wave emission, microjet penetration into the stratum corneum, and impact of microjet on the stratum corneum are considered. By relating the mechanical effects of these events on the stratum corneum structure, the relationship between the number of cavitation events and collapse pressures with experimentally measured increase in skin permeability was established. Theoretical predictions were compared to experimentally measured parameters of cavitation events.

  5. Further investigations on the role of ascorbic acid in stratum corneum lipid models after UV exposure.

    Science.gov (United States)

    Trommer, Hagen; Böttcher, Rolf; Huschka, Christoph; Wohlrab, Wolfgang; Neubert, Reinhard H H

    2005-08-01

    This study is the continuation of our research into vitamin C and its possible effects on human skin after topical administration. The effects of ascorbic acid, iron ions and UV irradiation on stratum corneum lipid models were investigated. The lipid models used were: a simple system (linolenic acid dispersion), a complex system (liposomes consisting of dipalmitoylphosphatidylcholine, cholesterol and linolenic acid) and complex systems with additionally incorporated ceramides (types III and IV). The lipid peroxidation was quantified by the thiobarbituric acid assay. A human adult low-calcium high-temperature (HaCaT) keratinocytes cell culture was used as a second in-vitro model. The amount of intracellular peroxides was determined by measuring the fluorescence intensity using the dihydrorhodamine 123 assay. Electron paramagnetic resonance spectroscopy was used to study the influence of ascorbic acid and iron ions on the signal intensity of 5-doxylstearic acid during UV exposure. Ascorbic acid showed prooxidative properties in the thiobarbituric acid assay whereas cell protection was measured in the HaCaT keratinocytes experiments. Electron paramagnetic resonance investigations revealed different extents of free radical production generated by iron ions, ascorbic acid and UV irradiation. In evaluating the results from this study new aspects of the mechanism of lipid damage caused by these three factors were suggested, transcending the simple redox behaviour of ascorbic acid.

  6. Study on the lipid organization of stratum corneum lipid models by (cryo-) electron diffraction

    NARCIS (Netherlands)

    Pilgram, GSK; Pelt, AMEV; Oostergetel, GT; Koerten, HK; Bouwstra, JA

    The barrier function of the skin resides in the stratum corneum (SC), This outermost layer consists of protein-rich corneocytes and lipid-rich intercellular domains. These domains form the rate-limiting step for transepidermal water loss and the penetration of substances from the environment. To

  7. Modeling the Effects of Lipid Composition on Stratum Corneum Bilayers Using Molecular Dynamics Simulations

    Science.gov (United States)

    Huzil, J. Torin; Sivaloganathan, Siv; Kohandel, Mohammad; Foldvari, Marianna

    2011-11-01

    The advancement of dermal and transdermal drug delivery requires the development of delivery systems that are suitable for large protein and nucleic acid-based therapeutic agents. However, a complete mechanistic understanding of the physical barrier properties associated with the epidermis, specifically the membrane structures within the stratum corneum, has yet to be developed. Here, we describe the assembly and computational modeling of stratum corneum lipid bilayers constructed from varying ratios of their constituent lipids (ceramide, free fatty acids and cholesterol) to determine if there is a difference in the physical properties of stratum corneum compositions.

  8. Development of a stratum corneum substitute for in vitro percutaneous penetration studies : a skin barrier model comprising synthetic stratum corneum lipids

    NARCIS (Netherlands)

    Jager, Miranda Wilhelmina de

    2006-01-01

    The research outlined in this thesis was focused on the development of a skin barrier model, which can substitute for stratum corneum in diffusion studies. This so-called stratum corneum substitute (SCS) was prepared with reconstituted SC lipids (cholesterol, free fatty acids and ceramides) on a

  9. Validation of Cyanoacrylate Method for Collection of Stratum Corneum in Human Skin for Lipid Analysis

    DEFF Research Database (Denmark)

    Jungersted, JM; Hellgren, Lars; Drachmann, Tue

    2010-01-01

    Background and Objective: Lipids in the stratum corneum (SC) are of major importance for the skin barrier function. Many different methods have been used for the collection of SC for the analysis of SC lipids. The objective of the present study was to validate the cyanoacrylate method for the col......Background and Objective: Lipids in the stratum corneum (SC) are of major importance for the skin barrier function. Many different methods have been used for the collection of SC for the analysis of SC lipids. The objective of the present study was to validate the cyanoacrylate method...

  10. Thermodynamic clarification of interaction between antiseptic compounds and lipids consisting of stratum corneum

    International Nuclear Information System (INIS)

    Aki, Hatsumi; Kawasaki, Yuhsuke

    2004-01-01

    The interactions of antiseptic compounds with quaternary ammonium, such as benzalkonium chloride (BC), benzethonium chloride (BZC), dodecyldiaminoethyl-glycine hydrochloride (AEG), and chlorhexidine gluconate (CHG), with components of the stratum corneum were investigated by isothermal titration calorimetry at pH 7.5 and 25 deg. C. The different mechanisms for their permeation to stratum corneum were clarified. Cationic surfactants of BC and BZC bound to cholesterol and cholesterol sulfate with high affinity (10 5 -10 6 M -1 ) to extract endogenous cholesterol and its derivatives from the stratum corneum and penetrated via an intercellular route. CHG also bound to cholesterol and accumulated in the stratum corneum without removing endogenous cholesterol. On the other hand, an amphoteric surfactant of AEG seemed to be incorporated into the lipid bilayer and bound to ceramide with its polar end close to the lipid polar heads by hydrophobic interaction

  11. Thermodynamic clarification of interaction between antiseptic compounds and lipids consisting of stratum corneum

    Energy Technology Data Exchange (ETDEWEB)

    Aki, Hatsumi; Kawasaki, Yuhsuke

    2004-06-24

    The interactions of antiseptic compounds with quaternary ammonium, such as benzalkonium chloride (BC), benzethonium chloride (BZC), dodecyldiaminoethyl-glycine hydrochloride (AEG), and chlorhexidine gluconate (CHG), with components of the stratum corneum were investigated by isothermal titration calorimetry at pH 7.5 and 25 deg. C. The different mechanisms for their permeation to stratum corneum were clarified. Cationic surfactants of BC and BZC bound to cholesterol and cholesterol sulfate with high affinity (10{sup 5}-10{sup 6} M{sup -1}) to extract endogenous cholesterol and its derivatives from the stratum corneum and penetrated via an intercellular route. CHG also bound to cholesterol and accumulated in the stratum corneum without removing endogenous cholesterol. On the other hand, an amphoteric surfactant of AEG seemed to be incorporated into the lipid bilayer and bound to ceramide with its polar end close to the lipid polar heads by hydrophobic interaction.

  12. Lipid composition of the stratum corneum and cutaneous water loss in birds along an aridity gradient

    NARCIS (Netherlands)

    Champagne, Alex M.; Munoz-Garcia, Agusti; Shtayyeh, Tamer; Tieleman, B. Irene; Hegemann, Arne; Clement, Michelle E.; Williams, Joseph B.

    2012-01-01

    Intercellular and covalently bound lipids within the stratum corneum (SC), the outermost layer of the epidermis, are the primary barrier to cutaneous water loss (CWL) in birds. We compared CWL and intercellular SC lipid composition in 20 species of birds from desert and mesic environments.

  13. Interactions of Inertial Cavitation Bubbles with Stratum Corneum Lipid Bilayers during Low-Frequency Sonophoresis

    OpenAIRE

    Tezel, Ahmet; Mitragotri, Samir

    2003-01-01

    Interactions of acoustic cavitation bubbles with biological tissues play an important role in biomedical applications of ultrasound. Acoustic cavitation plays a particularly important role in enhancing transdermal transport of macromolecules, thereby offering a noninvasive mode of drug delivery (sonophoresis). Ultrasound-enhanced transdermal transport is mediated by inertial cavitation, where collapses of cavitation bubbles microscopically disrupt the lipid bilayers of the stratum corneum. In...

  14. The important role of stratum corneum lipids for the cutaneous barrier function.

    Science.gov (United States)

    van Smeden, J; Janssens, M; Gooris, G S; Bouwstra, J A

    2014-03-01

    The skin protects the body from unwanted influences from the environment as well as excessive water loss. The barrier function of the skin is located in the stratum corneum (SC). The SC consists of corneocytes embedded in a lipid matrix. This lipid matrix is crucial for the lipid skin barrier function. This paper provides an overview of the reported SC lipid composition and organization mainly focusing on healthy and diseased human skin. In addition, an overview is provided on the data describing the relation between lipid modulations and the impaired skin barrier function. Finally, the use of in vitro lipid models for a better understanding of the relation between the lipid composition, lipid organization and skin lipid barrier is discussed. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Programmable fusion of liposomes mediated by lipidated PNA

    DEFF Research Database (Denmark)

    Rabe, A; Löffler, P M G; Ries, O

    2017-01-01

    We recently reported a DNA-programmed fusion cascade enabling the use of liposomes as nanoreactors for compartmentalized chemical reactions. This communication reports an alternative and robust strategy based on lipidated peptide nucleic acids (LiPs). LiPs enabled fusion of liposomes with remarka...... with remarkable 31% efficiency at 50 °C with low leakage (5%)....

  16. Role of ascorbic acid in stratum corneum lipid models exposed to UV irradiation.

    Science.gov (United States)

    Trommer, Hagen; Böttcher, Roif; Pöppl, Andreas; Hoentsch, Joachim; Wartewig, Siegfried; Neubert, Reinhard H H

    2002-07-01

    The effects of ascorbic acid on Stratum corneum lipid models following ultraviolet irradiation were studied adding iron ions as transition metal catalysts. Lipid peroxidation was quantified by the thiobarbituric acid assay. The qualitative changes were studied on a molecular level by mass spectrometry. To elucidate the nature of free radical involvement we carried out electron paramagnetic resonance studies. The influence of ascorbic acid on the concentration of hydroxyl radicals was examined using the spin trapping technique. Moreover, we checked the vitamin's ability to react with stable radicals. Ascorbic acid was found to have prooxidative effects in all lipid systems in a concentration dependent manner. The degradation products of ascorbic acid after its prooxidative action were detected. The concentration of the hydroxyl radicals in the Fenton assay was decreased by ascorbic acid. The quantification assay of 2,2-diphenyl-1-picrylhydrazyl hydrate showed reduced concentration levels of the stable radical caused by ascorbic acid. Considering human skin and its constant exposure to UV light and oxygen, an increased pool of iron ions in irradiated skin and the depletion of co-antioxidants, the administration of ascorbic acid in cosmetic formulations or in sunscreens could unfold adverse effects among the Stratum corneum lipids.

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

    International Nuclear Information System (INIS)

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

    1995-01-01

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

  18. Lipid composition of the stratum corneum and cutaneous water loss in birds along an aridity gradient.

    Science.gov (United States)

    Champagne, Alex M; Muñoz-Garcia, Agustí; Shtayyeh, Tamer; Tieleman, B Irene; Hegemann, Arne; Clement, Michelle E; Williams, Joseph B

    2012-12-15

    Intercellular and covalently bound lipids within the stratum corneum (SC), the outermost layer of the epidermis, are the primary barrier to cutaneous water loss (CWL) in birds. We compared CWL and intercellular SC lipid composition in 20 species of birds from desert and mesic environments. Furthermore, we compared covalently bound lipids with CWL and intercellular lipids in the lark family (Alaudidae). We found that CWL increases in birds from more mesic environments, and this increase was related to changes in intercellular SC lipid composition. The most consistent pattern that emerged was a decrease in the relative amount of cerebrosides as CWL increased, a pattern that is counterintuitive based on studies of mammals with Gaucher disease. Although covalently bound lipids in larks did not correlate with CWL, we found that covalently bound cerebrosides correlated positively with intercellular cerebrosides and intercellular cholesterol ester, and intercellular cerebrosides correlated positively with covalently bound free fatty acids. Our results led us to propose a new model for the organization of lipids in the avian SC, in which the sugar moieties of cerebrosides lie outside of intercellular lipid layers, where they may interdigitate with adjacent intercellular cerebrosides or with covalently bound cerebrosides.

  19. Stratum corneum lipids, skin barrier function and filaggrin mutations in patients with atopic eczema

    DEFF Research Database (Denmark)

    Høgh, Julie Kaae; Hellgren, Lars; Jungersted, JM

    2010-01-01

    chromatography. In addition, TEWL, erythema, skin hydration and pH were measured. In 27 of the 49 individuals, a 24-h irritation patch test with sodium lauryl sulphate was performed. For the analysis, both the AD group and the control group were stratified by FLG mutation status (FLGmut/FLGwt). Results......Background: Prior to the discovery of filaggrin (FLG) mutations, evidence for an impaired skin barrier in atopic dermatitis (AD) has been documented, and changes in ceramide profile, altered skin pH and increased trans-epidermal water loss (TEWL) in patients with AD have been reported. Until now......, no studies have analysed stratum corneum (SC) lipids combined with skin barrier parameters in subjects of known FLG genotype. Methods: A cohort of 49 German individuals genotyped for the most common FLG mutations (R501X, 2282del4) had SC samples taken for lipid analysis by high-performance thin layer...

  20. Rapid Quantification and Validation of Lipid Concentrations within Liposomes

    Directory of Open Access Journals (Sweden)

    Carla B. Roces

    2016-09-01

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

  1. Natural moisturizing factors (NMF) in the stratum corneum (SC). I. Effects of lipid extraction and soaking.

    Science.gov (United States)

    Robinson, Marisa; Visscher, Marty; Laruffa, Angela; Wickett, Randy

    2010-01-01

    Natural moisturizing factor (NMF) is essential for appropriate stratum corneum hydration, barrier homeostasis, desquamation, and plasticity. It is formed from filaggrin proteolysis to small, hygroscopic molecules including amino acids. We hypothesized that common lipid extraction and soaking in water would alter the level of NMF in the upper SC and its biophysical properties. A novel method of measuring and quantifying the amino acid components of NMF is presented. Adhesive tapes were used to collect samples of the stratum corneum (SC) and were extracted with 6mM perchloric acid for analysis by reverse-phase HPLC. HPLC results were standardized to the amount of protein removed by the tapes. An increase in NMF was found with increased SC depth. Also, the combination of extraction and soaking was found to increase NMF loss relative to control or to extraction or soaking alone. Our results indicate that common skin care practices significantly influence the water binding materials in the upper SC. The findings have implications for the evaluation and formulation of skin care products.

  2. Presence and persistence of a highly ordered lipid phase state in the avian stratum corneum.

    Science.gov (United States)

    Champagne, Alex M; Pigg, Victoria A; Allen, Heather C; Williams, Joseph B

    2018-06-07

    To survive high temperatures in a terrestrial environment, animals must effectively balance evaporative heat loss and water conservation. In passerine birds, cutaneous water loss (CWL) is the primary avenue of water loss at thermoneutral temperatures and increases slightly as ambient temperature increases, indicating a change in the permeability of the skin. In the stratum corneum (SC), the outermost layer of the skin, lipids arranged in layers called lamellae serve as the primary barrier to CWL in birds. The permeability of these lamellae depends in large part on the ability of lipid molecules to pack closely together in an ordered orthorhombic phase state. However, as temperature increases, lipids of the SC become more disordered, and may pack in more permeable hexagonal or liquid crystalline phase states. In this study, we used Fourier transform infrared spectroscopy to monitor the phase state of lipids in the SC of house sparrows ( Passer domesticus ) at skin temperatures ranging from 25 to 50°C. As temperature increased, lipids became slightly more disordered, but remained predominantly in the orthorhombic phase, consistent with the small increase in CWL observed in house sparrows as ambient temperature increases. These results differ considerably from studies on mammalian SC, which find a predominantly hexagonal arrangement of lipids at temperatures above 37°C, and the increased order in avian SC may be explained by longer lipid chain length, scarcity of cholesterol and the presence of cerebrosides. Our results lend further insight into the arrangement and packing of individual lipid molecules in avian SC. © 2018. Published by The Company of Biologists Ltd.

  3. Stratum corneum lipid organization as observed by atomic force, confocal and two-photon excitation fluorescence microscopy

    DEFF Research Database (Denmark)

    Norlén, Lars; Plasencia Gil, Maria Inés; Bagatolli, Luis

    2008-01-01

    -related biophysical techniques (e.g. atomic force microscopy and confocal/two-photon excitation fluorescence microscopy), it was recently shown that reconstituted membranes composed of extracted decontaminated human stratum corneum lipids do not form a fluid phase, but exclusively a single-gel phase that segregates...

  4. Effect of chemical permeation enhancers on stratum corneum barrier lipid organizational structure and interferon alpha permeability.

    Science.gov (United States)

    Moghadam, Shadi H; Saliaj, Evi; Wettig, Shawn D; Dong, Chilbert; Ivanova, Marina V; Huzil, J Torin; Foldvari, Marianna

    2013-06-03

    The outermost layer of the skin, known as the stratum corneum (SC), is composed of dead corneocytes embedded in an intercellular lipid matrix consisting of ceramides, free fatty acids, and cholesterol. The high level of organization within this matrix protects the body by limiting the permeation of most compounds through the skin. While essential for its protective functions, the SC poses a significant barrier for the delivery of topically applied pharmaceutical agents. Chemical permeation enhancers (CPEs) can increase delivery of small drug compounds into the skin by interacting with the intercellular lipids through physical processes including extraction, fluidization, increased disorder, and phase separation. However, it is not clear whether these same mechanisms are involved in delivery of biotherapeutic macromolecules, such as proteins. Here we describe the effect of three categories of CPEs {solvents [ethanol, propylene glycol, diethylene glycol monoethyl ether (transcutol), oleic acid], terpenes [menthol, nerol, camphor, methyl salicylate], and surfactants [Tween 80, SDS, benzalkonium chloride, polyoxyl 40 hydrogenated castor oil (Cremophor RH40), didecyldimethylammonium bromide (DDAB), didecyltrimethylammonium bromide (DTAB)]} on the lipid organizational structure of human SC as determined by X-ray scattering studies. Small- and wide-angle X-ray scattering studies were conducted to correlate the degree of structural changes and hydrocarbon chain packing in SC lipids caused by these various classes of CPEs to the extent of permeation of interferon alpha-2b (IFNα), a 19 kDa protein drug, into human skin. With the exception of solvents, propylene glycol and ethanol, all classes of CPEs caused increased disordering of lamellar and lateral packing of lipids. We observed that the highest degree of SC lipid disordering was caused by surfactants (especially SDS, DDAB, and DTAB) followed by terpenes, such as nerol. Interestingly, in vitro skin permeation studies

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

    Science.gov (United States)

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

    2018-03-07

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

  6. Molecular dynamics simulations of stratum corneum lipid mixtures: A multiscale perspective.

    Science.gov (United States)

    Moore, Timothy C; Iacovella, Christopher R; Leonhard, Anne C; Bunge, Annette L; McCabe, Clare

    2018-03-29

    The lipid matrix of the stratum corneum (SC) layer of skin is essential for human survival; it acts as a barrier to prevent rapid dehydration while keeping potentially hazardous material outside the body. While the composition of the SC lipid matrix is known, the molecular-level details of its organization are difficult to infer experimentally, hindering the discovery of structure-property relationships. To this end, molecular dynamics simulations, which give molecular-level resolution, have begun to play an increasingly important role in understanding these relationships. However, most simulation studies of SC lipids have focused on preassembled bilayer configurations, which, owing to the slow dynamics of the lipids, may influence the final structure and hence the calculated properties. Self-assembled structures would avoid this dependence on the initial configuration, however, the size and length scales involved make self-assembly impractical to study with atomistic models. Here, we report on the development of coarse-grained models of SC lipids designed to study self-assembly. Building on previous work, we present the interactions between the headgroups of ceramide and free fatty acid developed using the multistate iterative Boltzmann inversion method. Validation of the new interactions is performed with simulations of preassembled bilayers and good agreement between the atomistic and coarse-grained models is found for structural properties. The self-assembly of mixtures of ceramide and free fatty acid is investigated and both bilayer and multilayer structures are found to form. This work therefore represents a necessary step in studying SC lipid systems on multiple time and length scales. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    1980-01-01

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

  8. Stratum Corneum Lipids: Their Role for the Skin Barrier Function in Healthy Subjects and Atopic Dermatitis Patients.

    Science.gov (United States)

    van Smeden, Jeroen; Bouwstra, Joke A

    2016-01-01

    Human skin acts as a primary barrier between the body and its environment. Crucial for this skin barrier function is the lipid matrix in the outermost layer of the skin, the stratum corneum (SC). Two of its functions are (1) to prevent excessive water loss through the epidermis and (2) to avoid that compounds from the environment permeate into the viable epidermal and dermal layers and thereby provoke an immune response. The composition of the SC lipid matrix is dominated by three lipid classes: cholesterol, free fatty acids and ceramides. These lipids adopt a highly ordered, 3-dimensional structure of stacked densely packed lipid layers (lipid lamellae): the lateral and lamellar lipid organization. The way in which these lipids are ordered depends on the composition of the lipids. One very common skin disease in which the SC lipid barrier is affected is atopic dermatitis (AD). This review addresses the SC lipid composition and organization in healthy skin, and elaborates on how these parameters are changed in lesional and nonlesional skin of AD patients. Concerning the lipid composition, the changes in the three main lipid classes and the importance of the carbon chain lengths of the lipids are discussed. In addition, this review addresses how these changes in lipid composition induce changes in lipid organization and subsequently correlate with an impaired skin barrier function in both lesional and nonlesional skin of these patients. Furthermore, the effect of filaggrin and mutations in the filaggrin gene on the SC lipid composition is critically discussed. Also, the breakdown products of filaggrin, the natural moisturizing factor molecules and its relation to SC-pH is described. Finally, the paper discusses some major changes in epidermal lipid biosynthesis in patients with AD and other related skin diseases, and how inflammation has a deteriorating effect on the SC lipids and SC biosynthesis. The review ends with perspectives on future studies in relation to

  9. Structure of lamellar lipid domains and corneocyte envelopes of murine stratum corneum. An X-ray diffraction study

    International Nuclear Information System (INIS)

    White, S.H.; Mirejovsky, D.; King, G.I.

    1988-01-01

    The lipid of the outermost layer of the skin is confined largely to the extracellular spaces surrounding the corneocytes of the stratum corneum where it forms a multilamellar adhesive matrix to act as the major permeability barrier of the skin. Knowledge of the molecular architecture of these intercellular domains is important for understanding various skin pathologies and their treatment, percutaneous drug delivery, and the cosmetic maintenance of the skin. The authors have surveyed by X-ray diffraction the structure of the intercellular domains and the extracted lipids of murine stratum corneum (SC) at 25, 45, and 70 0 C which are temperatures in the vicinity of known thermal phase transitions. The intercellular domains produce lamellar diffraction patterns with a Bragg spacing of 131 +/- 2 A. Lipid extracted from the SC and dispersed in excess water does not produce a simple lamellar diffraction pattern at any temperature studied, however. This and other facts suggest that another component, probably a protein, must be present to control the architecture of the intercellular lipid domains. They have also obtained diffraction patterns attributable to the protein envelopes of the corneocytes. The patterns suggest a β-pleated sheet organizational scheme. No diffraction patterns were observed that could be attributed to keratin

  10. 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.

  11. Ultraviolet radiation-induced lipid peroxidation in liposomal membrane: modification by capsaicin

    Energy Technology Data Exchange (ETDEWEB)

    De, A. K.; Ghosh, J. J.; Mandal, T. K. [University College of Science, Department of Biochemistry, 35 Ballygunge Circular Road, Calcutta 700-019 (India)

    1993-07-01

    Ultraviolet-radiation has been reported to cause lipid peroxidation in the liposomal membrane. In the present study, treatment with capsaicin, (8-methyl-n-vanillyl-6-nonenamide), the pungent principle of red hot pepper, was shown to modify UV-induced lipid peroxidation in the liposomal membrane. Treatment with low doses of capsaicin (less than 0.1 μg/mL of phosphatidyl choline liposome) produced a significant increase in UV-induced lipid peroxidation, while high doses (0.1-0.5 μg/mL of PC liposome) caused a significant decrease of UV-induced peroxidation.

  12. Ultraviolet radiation-induced lipid peroxidation in liposomal membrane: modification by capsaicin

    International Nuclear Information System (INIS)

    De, A.K.; Ghosh, J.J.; Mandal, T.K.

    1993-01-01

    Ultraviolet-radiation has been reported to cause lipid peroxidation in the liposomal membrane. In the present study, treatment with capsaicin, (8-methyl-n-vanillyl-6-nonenamide), the pungent principle of red hot pepper, was shown to modify UV-induced lipid peroxidation in the liposomal membrane. Treatment with low doses of capsaicin (less than 0.1 μg/mL of phosphatidyl choline liposome) produced a significant increase in UV-induced lipid peroxidation, while high doses (0.1-0.5 μg/mL of PC liposome) caused a significant decrease of UV-induced peroxidation

  13. Hydration effects on the barrier function of stratum corneum lipids: Raman analysis of ceramides 2, III and 5.

    Science.gov (United States)

    Tfayli, Ali; Jamal, Dima; Vyumvuhore, Raoul; Manfait, Michel; Baillet-Guffroy, Arlette

    2013-11-07

    The stratum corneum is the outermost layer of the skin; its barrier function is highly dependent on the composition and the structure as well as the organization of lipids in its extracellular matrix. Ceramides, free fatty acids and cholesterol represent the major lipid classes present in this matrix. They play an important role in maintaining the normal hydration levels required for the normal physiological function. Despite the advancement in the understanding of the structure, composition and the function of the stratum corneum (SC), the concern of "dry skin" remains important in dermatology and care research. Most studies focus on the quantification of water in the skin using different techniques including Raman spectroscopy, while the studies that investigate the effect of hydration on the quality of the barrier function of the skin are limited. Raman spectroscopy provides structural, conformational and organizational information that could help elucidate the effect of hydration on the barrier function of the skin. In order to assess the effect of relative humidity on the lipid barrier function; we used Raman spectroscopy to follow-up the evolution of the conformation and the organization of three synthetic ceramides (CER) differing from each other by the nature of their polar heads (sphingosine, phytosphingosine and α hydroxyl sphingosine), CER 2, III and 5 respectively. CER III and 5 showed a more compact and ordered organization with stronger polar interactions at intermediate relative humidity values, while CER 2 showed opposite tendencies to those observed with CER III and 5.

  14. Atomic Force Microscopy Study on the Stiffness of Nanosized Liposomes Containing Charged Lipids.

    Science.gov (United States)

    Takechi-Haraya, Yuki; Goda, Yukihiro; Sakai-Kato, Kumiko

    2018-06-18

    It has recently been recognized that the mechanical properties of lipid nanoparticles play an important role during in vitro and in vivo behaviors such as cellular uptake, blood circulation, and biodistribution. However, there have been no quantitative investigations of the effect of commonly used charged lipids on the stiffness of nanosized liposomes. In this study, by means of atomic force microscopy (AFM), we quantified the stiffness of nanosized liposomes composed of neutrally charged lipids combined with positively or negatively charged lipids while simultaneously imaging the liposomes in aqueous medium. Our results showed that charged lipids, whether negatively or positively charged, have the effect of reducing the stiffness of nanosized liposomes, independently of the saturation degree of the lipid acyl chains; the measured stiffness values of liposomes containing charged lipids are 30-60% lower than those of their neutral counterpart liposomes. In addition, we demonstrated that the Laurdan generalized polarization values, which are related to the hydration degree of the liposomal membrane interface and often used as a qualitative indicator of liposomal membrane stiffness, do not directly correlate with the physical stiffness values of the liposomes prepared in this study. However, our results indicate that direct quantitative AFM measurement is a valuable method to gain molecular-scale information about how the hydration degree of liposomal interfaces reflects (or does not reflect) liposome stiffness as a macroscopic property. Our AFM method will contribute to the quantitative characterization of the nano-bio interaction of nanoparticles and to the optimization of the lipid composition of liposomes for clinical use.

  15. Developmental plasticity of cutaneous water loss and lipid composition in stratum corneum of desert and mesic nestling house sparrows.

    Science.gov (United States)

    Muñoz-Garcia, Agustí; Williams, Joseph B

    2008-10-07

    Intercellular lipids of the stratum corneum (SC), the outer layer of the epidermis, form a barrier to water vapor diffusion through the skin. Previously, we measured cutaneous water loss (CWL) and lipid composition of the SC of adult house sparrows from two populations, one living in the deserts of Saudi Arabia and another living in mesic Ohio. Adult desert house sparrows had a lower CWL, a lower proportion of free fatty acids, and a higher proportion of ceramides and cerebrosides in the SC compared with mesic sparrows. In this study, we investigated developmental plasticity of CWL and lipid composition of the SC in desert and mesic nestling house sparrows reared in low and high humidity and compared our results with previous work on adults. We measured CWL of nestlings and analyzed the lipid composition of the SC using thin-layer chromatography. We showed that nestling house sparrows from both localities had higher CWL than adults in their natural environment, a result of major modifications of the lipid composition of the SC. The expression of plasticity in CWL seems to be a response to opposed selection pressures, thermoregulation and water conservation, at different life stages, on which regulation of CWL plays a crucial role. Desert nestlings showed a greater degree of plasticity in CWL and lipid composition of the SC than did mesic nestlings, a finding consistent with the idea that organisms exposed to more environmental stress ought to be more plastic than individuals living in more benign environments.

  16. 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.

  17. Dynamical and structural properties of lipid membranes in relation to liposomal drug delivery systems

    DEFF Research Database (Denmark)

    Jørgensen, Kent; Høyrup, Lise Pernille Kristine; Pedersen, Tina B.

    2001-01-01

    The structural and dynamical properties of DPPC liposomes containing lipopolymers (PEG-lipids) and charged DPPS lipids have been,studied in relation to the lipid membrane interaction of enzymes and peptides. The results suggest that both the lipid membrane structure and dynamics and in particular...

  18. Skin barrier response to occlusion of healthy and irritated skin: Differences in trans-epidermal water loss, erythema and stratum corneum lipids

    DEFF Research Database (Denmark)

    Jungersted, J.M.; Høgh, Julie Kaae; Hellgren, Lars

    2010-01-01

    been damaged by either sodium lauryl sulfate (SLS) or tape stripping, respectively, was determined and compared with that of to non-occluded pre-damaged skin. Skin barrier function was assessed by measurements of trans-epidermal water loss (TEWL) and erythema. In study A, stratum corneum lipids were...

  19. 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.

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

    International Nuclear Information System (INIS)

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

    1998-01-01

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

  1. Effect of Ceramide Tail Length on the Structure of Model Stratum Corneum Lipid Bilayers.

    Science.gov (United States)

    Moore, Timothy C; Hartkamp, Remco; Iacovella, Christopher R; Bunge, Annette L; McCabe, Clare

    2018-01-09

    Lipid bilayers composed of non-hydroxy sphingosine ceramide (CER NS), cholesterol (CHOL), and free fatty acids (FFAs), which are components of the human skin barrier, are studied via molecular dynamics simulations. Since mixtures of these lipids exist in dense gel phases with little molecular mobility at physiological conditions, care must be taken to ensure that the simulations become decorrelated from the initial conditions. Thus, we propose and validate an equilibration protocol based on simulated tempering, in which the simulation takes a random walk through temperature space, allowing the system to break out of metastable configurations and hence become decorrelated from its initial configuration. After validating the equilibration protocol, which we refer to as random-walk molecular dynamics, the effects of the lipid composition and ceramide tail length on bilayer properties are studied. Systems containing pure CER NS, CER NS + CHOL, and CER NS + CHOL + FFA, with the CER NS fatty acid tail length varied within each CER NS-CHOL-FFA composition, are simulated. The bilayer thickness is found to depend on the structure of the center of the bilayer, which arises as a result of the tail-length asymmetry between the lipids studied. The hydrogen bonding between the lipid headgroups and with water is found to change with the overall lipid composition, but is mostly independent of the CER fatty acid tail length. Subtle differences in the lateral packing of the lipid tails are also found as a function of CER tail length. Overall, these results provide insight into the experimentally observed trend of altered barrier properties in skin systems where there are more CERs with shorter tails present. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  2. Investigation of the interaction between modified ISCOMs and stratum corneum lipid model systems

    DEFF Research Database (Denmark)

    Madsen, Henriette Baun; Arboe-Andersen, Helle M.; Rozlosnik, Noemi

    2010-01-01

    The modified ISCOMs, so-called Posintro (TM) nanoparticles, provide an opportunity for altering the surface charge of the particles, which influences their affinity for the negatively charged antigen sites, cell membranes and lipids in the skin. Hypothetically, this increases the passage of the I...

  3. Surface modified liposomes by mannosylated conjugates anchored via the adamantyl moiety in the lipid bilayer.

    Science.gov (United States)

    Stimac, Adela; Segota, Suzana; Dutour Sikirić, Maja; Ribić, Rosana; Frkanec, Leo; Svetličić, Vesna; Tomić, Srđanka; Vranešić, Branka; Frkanec, Ruža

    2012-09-01

    The aim of the present study was to encapsulate mannosylated 1-aminoadamantane and mannosylated adamantyltripeptides, namely [(2R)-N-(adamant-1-yl)-3-(α,β-d-mannopyranosyloxy)-2-methylpropanamide and (2R)-N-[3-(α-d-mannopyranosyloxy)-2-methylpropanoyl]-d,l-(adamant-2-yl)glycyl-l-alanyl-d-isoglutamine] in liposomes. The characterization of liposomes, size and surface morphology was performed using dynamic light scattering (DLS) and atomic force microscopy (AFM). The results have revealed that the encapsulation of examined compounds changes the size and surface of liposomes. After the concanavalin A (ConA) was added to the liposome preparation, increase in liposome size and their aggregation has been observed. The enlargement of liposomes was ascribed to the specific binding of the ConA to the mannose present on the surface of the prepared liposomes. Thus, it has been shown that the adamantyl moiety from mannosylated 1-aminoadamantane and mannosylated adamantyltripeptides can be used as an anchor in the lipid bilayer for carbohydrate moiety exposed on the liposome surface. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2012-12-01

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

  5. Calcipotriol delivery into the skin with PEGylated liposomes

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

    Clausen, Mads Hartvig

    2011-01-01

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

  7. Curvature effects on lipid packing and dynamics in liposomes revealed by coarse grained molecular dynamics simulations

    NARCIS (Netherlands)

    Risselada, H. Jelger; Marrink, Siewert J.

    2009-01-01

    The molecular packing details of lipids in planar bilayers are well characterized. For curved bilayers, however, little data is available. In this paper we study the effect of temperature and membrane composition on the structural and dynamical properties of a liposomal membrane in the limit of high

  8. An Efficient Glycoblotting-Based Analysis of Oxidized Lipids in Liposomes and a Lipoprotein.

    Science.gov (United States)

    Furukawa, Takayuki; Hinou, Hiroshi; Takeda, Seiji; Chiba, Hitoshi; Nishimura, Shin-Ichiro; Hui, Shu-Ping

    2017-10-05

    Although widely occurring lipid oxidation, which is triggered by reactive oxygen species (ROS), produces a variety of oxidized lipids, practical methods to efficiently analyze oxidized lipids remain elusive. Herein, it is shown that the glycoblotting platform can be used to analyze oxidized lipids. Analysis is based on the principle that lipid aldehydes, one of the oxidized lipid species, can be captured selectively, enriched, and detected. Moreover, 3-methyl-1-p-tolyltriazene (MTT) methylates phosphoric and carboxylic acids, and this MTT-mediated methylation is, in combination with conventional tandem mass spectrometry (MS/MS) analysis, an effective method for the structural analysis of oxidized lipids. By using three classes of standards, liposomes, and a lipoprotein, it is demonstrated that glycoblotting represents a powerful approach for focused lipidomics, even in complex macromolecules. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Chlorophyll a and chlorophyllide a inside liposomes made of saturated and unsaturated lipids: A possible impact of the lipids microenvironment

    Directory of Open Access Journals (Sweden)

    Petrović Sanja M.

    2014-01-01

    Full Text Available The aim of this work was to examine a possible impact of liposomes lipids microenvironment, dictated by a chemical composition of the fatty acid branches, on incorporation and spectral behaviour of chlorophyll a, and its derivative, chlorophyllide a inside small liposomes. The liposomes with the incorporated chlorophylls were made of dimirystoyl phosphatidylcholine (DMPC, and unsaturated phosphatidylcholine (PC, containing significant fractions of unsaturated fatty acid moieties. In order to achieve the goal, both absorption and fluorescence polarization spectroscopy were applied, and the obtained data for the two incorporated pigments, which play a role of molecular sensors, were compared. In addition, quercetin, a well-known antioxidant, was used as the (chlorophylls emission quencher, in order to estimate the type of environment sensed by the two pigments for the two liposomes that differ in chemical composition. The results, based primarily on fluorescence polarization data have shown that the emissions as well as the emission quenching were notably affected by a change in the lipids’ chemical composition. That is an indirect proof of the impact of the liposomes microenvironment on the incorporated pigments’ spectral behaviour.[ Projekat Ministarstva nauke Republike Srbije, br. TR-34012 i br. OI-172044

  10. 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.

  11. An in vitro model to test relative antioxidant potential: Ultraviolet-induced lipid peroxidation in liposomes

    International Nuclear Information System (INIS)

    Pelle, E.; Maes, D.; Padulo, G.A.; Kim, E.K.; Smith, W.P.

    1990-01-01

    Since antioxidants have been shown to play a major role in preventing some of the effects of aging and photoaging in skin, it is important to study this phenomenon in a controlled manner. This was accomplished by developing a simple and reliable in vitro technique to assay antioxidant efficacy. Inhibition of peroxidation by antioxidants was used as a measure of relative antioxidant potential. Liposomes, high in polyunsaturated fatty acids (PUFA), were dispersed in buffer and irradiated with ultraviolet (UV) light. Irradiated liposomes exhibited a significantly higher amount of hydroperoxides than liposomes containing antioxidants in a dose- and concentration-dependent manner. Lipid peroxidation was determined spectrophotometrically by an increase in thiobarbituric acid reacting substances. To further substantiate the production of lipid peroxides, gas chromatography was used to measure a decrease in PUFA substrate. In order of decreasing antioxidant effectiveness, the following results were found among lipophilic antioxidants: BHA greater than catechin greater than BHT greater than alpha-tocopherol greater than chlorogenic acid. Among hydrophilic antioxidants, ascorbic acid and dithiothreitol were effective while glutathione was ineffective. In addition, ascorbic acid was observed to act synergistically with alpha-tocopherol, which is in agreement with other published reports on the interaction of these two antioxidants. Although peroxyl radical scavengers seem to be at a selective advantage in this liposomal/UV system, these results demonstrate the validity of this technique as an assay for measuring an antioxidant's potential to inhibit UV-induced peroxidation

  12. Cutaneous water loss and covalently bound lipids of the stratum corneum in nestling house sparrows (Passer domesticus L.) from desert and mesic habitats.

    Science.gov (United States)

    Clement, Michelle E; Muñoz-Garcia, Agustí; Williams, Joseph B

    2012-04-01

    Lipids of the stratum corneum (SC), the outer layer of the epidermis of birds and mammals, provide a barrier to water vapor diffusion through the skin. The SC of birds consists of flat dead cells, called corneocytes, and two lipid compartments: an intercellular matrix and a monolayer of covalently bound lipids (CBLs) attached to the outer surface of the corneocytes. We previously found two classes of sphingolipids, ceramides and cerebrosides, covalently bound to corneocytes in the SC of house sparrows (Passer domesticus L.); these lipids were associated with cutaneous water loss (CWL). In this study, we collected adult and nestling house sparrows from Ohio and nestlings from Saudi Arabia, acclimated them to either high or low humidity, and measured their rates of CWL. We also measured CWL for natural populations of nestlings from Ohio and Saudi Arabia, beginning when chicks were 2 days old until they fledged. We then evaluated the composition of the CBLs of the SC of sparrows using thin layer chromatography. We found that adult house sparrows had a greater diversity of CBLs in their SC than previously described. During ontogeny, nestling sparrows increased the amount of CBLs and developed their CBLs differently, depending on their habitat. Acclimating nestlings to different humidity regimes did not alter the ontogeny of the CBLs, suggesting that these lipids represent a fundamental component of SC organization that does not respond to short-term environmental change.

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

    Science.gov (United States)

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

    2015-09-15

    Cholesterol-based fluorescent lipids with ether linker were synthesized using NBD (Chol-E-NBD) or Rhodamine B (Chol-E-Rh), and the usefulnesses as fluorescent probes for tracing cholesterol-based liposomes were validated. The fluorescent intensities of liposomes containing these modified lipids were measured and observed under a microscope. Neither compound interfered with the expression of GFP plasmid, and live cell images were obtained without interferences. Changes in the fluorescent intensity of liposomes containing Chol-E-NBD were followed by flow cytometry for up to 24h. These fluorescent lipids could be useful probes for trafficking of cationic liposome-mediated gene delivery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Influence of polymer size, liposomal composition, surface charge, and temperature on the permeability of pH-sensitive liposomes containing lipid-anchored poly(2-ethylacrylic acid

    Directory of Open Access Journals (Sweden)

    Lu T

    2012-09-01

    Full Text Available Tingli Lu,1 Zhao Wang,2 Yufan Ma,1 Yang Zhang,2 Tao Chen1,21Key Laboratory for Space Bioscience and Biotechnology, School of Life Science, Northwestern Polytechnical University, 2Liposome Research Centre, Xi'an, ChinaBackground: Liposomes containing pH-sensitive polymers are promising candidates for the treatment of tumors and localized infection. This study aimed to identify parameters influencing the extent of contents release from poly(ethylacrylic acid (PEAA vesicles, focusing on the effects of polymer size, lipid composition, vesicle surface charge, and temperature.Methods: Anchored lipid pH-sensitive PEAA was synthesized using PEAA with a molecular weight of 8.4 kDa. PEAA vesicles were prepared by insertion of the lipid-anchored PEAA into preformed large unilamellar vesicles. The preformed liposomes were manipulated by varying the phosphocholine and cholesterol content, and by adding negative or positive charges to the liposomes. A calcein release assay was used to evaluate the effects of polymer size, liposome composition, surface charge, and temperature on liposomal permeability.Results: The release efficiency of the calcein-entrapped vesicles was found to be dependent on the PEAA polymer size. PEAA vesicles containing a phosphatidylcholine to cholesterol ratio of 60:40 (mol/mol released more than 80% of their calcein content when the molecular weight of PEAA was larger than 8.4 kDa. Therefore, the same-sized polymer of 8.4 kDa was used for the rest of study. The calcein release potential was found to decrease as the percentage of cholesterol increased and with an increase in the phosphocholine acyl chain length (DMPC . DPPC . DSPC. Negatively charged and neutral vesicles released similar amounts of calcein, whereas positively charged liposomes released a significant amount of their contents. pH-sensitive release was dependent on temperature. Dramatic content release was observed at higher temperatures.Conclusion: The observed

  15. Influence of the state of phase of lipid bilayer on the exposure of glucose residues on the surface of liposomes.

    Science.gov (United States)

    Villalva, Denise Gradella; Giansanti, Luisa; Mauceri, Alessandro; Ceccacci, Francesca; Mancini, Giovanna

    2017-11-01

    The presence of carbohydrate-binding proteins (i.e. lectins) on the surface of various bacterial strains and their overexpression in some tumor tissues makes the use of glycosylated liposomes a promising approach for the specific drug delivery in antibacterial and anti-cancer therapies. However, the functionalization of liposome surface with sugar moieties by glycosylated amphiphiles does not ensure the binding of sugar-coated vesicles with lectins. In fact, the composition and properties of lipid bilayer play a pivotal role in the exposure of sugar residues and in the interaction with lectins. The influence of the length of the hydrophilic spacer that links the sugar to liposome surface and of the presence of saturated or unsaturated phospholipids in the lipid bilayer on the ability of glucosylated liposomes to interact with a model lectin, Concanavalin A, was investigated. Our results demonstrate that both the chain length and the prensece of unsaturation, parameters that strongly affect the fluidity of the lipid bilayer, affect agglutination. In particular, agglutination is favored when liposomes are in the gel phase within a defined range of temperature. Moreover, the obtained results confirm that the length of the PEG spacer, that influences both lipid organization and the exposure of sugar moieties to the bulk, plays a crucial role in liposome/lectin interaction. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. 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.

  17. Red wine tannins fluidify and precipitate lipid liposomes and bicelles. A role for lipids in wine tasting?

    Science.gov (United States)

    Furlan, Aurélien L; Castets, Aurore; Nallet, Frédéric; Pianet, Isabelle; Grélard, Axelle; Dufourc, Erick J; Géan, Julie

    2014-05-20

    Sensory properties of red wine tannins are bound to complex interactions between saliva proteins, membranes taste receptors of the oral cavity, and lipids or proteins from the human diet. Whereas astringency has been widely studied in terms of tannin-saliva protein colloidal complexes, little is known about interactions between tannins and lipids and their implications in the taste of wine. This study deals with tannin-lipid interactions, by mimicking both oral cavity membranes by micrometric size liposomes and lipid droplets in food by nanometric isotropic bicelles. Deuterium and phosphorus solid-state NMR demonstrated the membrane hydrophobic core disordering promoted by catechin (C), epicatechin (EC), and epigallocatechin gallate (EGCG), the latter appearing more efficient. C and EGCG destabilize isotropic bicelles and convert them into an inverted hexagonal phase. Tannins are shown to be located at the membrane interface and stabilize the lamellar phases. These newly found properties point out the importance of lipids in the complex interactions that happen in the mouth during organoleptic feeling when ingesting tannins.

  18. Fluorescent Lipids: Functional Parts of Fusogenic Liposomes and Tools for Cell Membrane Labeling and Visualization

    Directory of Open Access Journals (Sweden)

    Christian Kleusch

    2012-01-01

    Full Text Available In this paper a rapid and highly efficient method for controlled incorporation of fluorescent lipids into living mammalian cells is introduced. Here, the fluorescent molecules have two consecutive functions: First, they trigger rapid membrane fusion between cellular plasma membranes and the lipid bilayers of their carrier particles, so called fusogenic liposomes, and second, after insertion into cellular membranes these molecules enable fluorescence imaging of cell membranes and membrane traffic processes. We tested the fluorescent derivatives of the following essential membrane lipids for membrane fusion: Ceramide, sphingomyelin, phosphocholine, phosphatidylinositol-bisphosphate, ganglioside, cholesterol, and cholesteryl ester. Our results show that all probed lipids could more efficiently be incorporated into the plasma membrane of living cells than by using other methods. Moreover, labeling occurred in a gentle manner under classical cell culture conditions reducing cellular stress responses. Staining procedures were monitored by fluorescence microscopy and it was observed that sphingolipids and cholesterol containing free hydroxyl groups exhibit a decreased distribution velocity as well as a longer persistence in the plasma membrane compared to lipids without hydroxyl groups like phospholipids or other artificial lipid analogs. After membrane staining, the fluorescent molecules were sorted into membranes of cell organelles according to their chemical properties and biological functions without any influence of the delivery system.

  19. Comparison of Linear and Hyperbranched Polyether Lipids for Liposome Shielding by 18F-Radiolabeling and Positron Emission Tomography.

    Science.gov (United States)

    Wagener, Karolin; Worm, Matthias; Pektor, Stefanie; Schinnerer, Meike; Thiermann, Raphael; Miederer, Matthias; Frey, Holger; Rösch, Frank

    2018-04-27

    Multifunctional and highly biocompatible polyether structures play a key role in shielding liposomes from degradation in the bloodstream, providing also multiple functional groups for further attachment of targeting moieties. In this work hyperbranched polyglycerol ( hbPG) bearing lipids with long alkyl chain anchor are evaluated with respect to steric stabilization of liposomes. The branched polyether lipids possess a hydrophobic bis(hexadecyl)glycerol membrane anchor for the liposomal membrane. hbPG was chosen as a multifunctional alternative to PEG, enabling the eventual linkage of multiple targeting vectors. Different hbPG lipids ( M n = 2900 and 5200 g mol -1 ) were examined. A linear bis(hexadecyl)glycerol-PEG lipid ( M n = 3000 g mol -1 ) was investigated as well, comparing hbPG and PEG with respect to shielding properties. Radiolabeling of the polymers was carried out using 1-azido-2-(2-(2-[ 18 F]fluoroethoxy)ethoxy)ethane ([ 18 F]F-TEG-N) 3 via copper-catalyzed alkyne-azide cycloaddition with excellent radiochemical yields exceeding 95%. Liposomes were prepared by the thin-film hydration method followed by repeated extrusion. Use of a custom automatic extrusion device gave access to reproducible sizes of the liposomes (hydrodynamic radius of 60-94 nm). The in vivo fate of the bis(hexadecyl)glycerol polyethers and their corresponding assembled liposome structures were evaluated via noninvasive small animal positron emission tomography (PET) imaging and biodistribution studies (1 h after injection and 4 h after injection) in mice. Whereas the main uptake of the nonliposomal polyether lipids was observed in the kidneys and in the bladder after 1 h due to rapid renal clearance, in contrast, the corresponding liposomes showed uptake in the blood pool as well as in organs with good blood supply, that is, heart and lung over the whole observation period of 4 h. The in vivo behavior of all three liposomal formulations was comparable, albeit with remarkable

  20. Electroporation of Skin Stratum Corneum Lipid Bilayer and Molecular Mechanism of Drug Transport: A Molecular Dynamics Study.

    Science.gov (United States)

    Gupta, Rakesh; Rai, Beena

    2018-04-30

    Skin electroporation has been used significantly to increase the drug permeation. However, molecular mechanism, which resulted in enhancement of flux through skin, is still not known. In this study, extensive atomistic molecular dynamics simulation of skin lipids (made up of ceramide (CER), cholesterol (CHOL) and free fatty acid (FFA)) have been performed at various external electric field. We show for the first time the pore formation in the skin lipid bilayer during the electroporation. We show the effect of applied external electrical field on the pore formation dynamics in lipid bilayer of different size and composition. The pore formation and resealing kinetics were different and was found to be highly dependent on the composition of skin lipid bilayer. The pore formation time decreased with increase in the bilayer size. The pore sustaining electric field was found to be in the range of 0.20-0.25 V/nm for equimolar CER, CHOL and FFA lipid bilayer. The skin lipid bilayer (1:1:1), sealed itself within 20 ns after the removal of external electric field. We also present the molecular mechanism of enhancement of drug permeation in the presence of external field as compared to the passive diffusion. The molecular level understanding obtained here could help in optimizing/designing the electroporation experiments for effective drug delivery. For a given skin composition and size of drug molecule, the combination of pore formation time and pore growth model can be used to know aproiri the desired electric field and time for application of electric field.

  1. Impact of the ceramide subspecies on the nanostructure of stratum corneum lipids using neutron scattering and molecular dynamics simulations. Part I: impact of CER[NS].

    Science.gov (United States)

    Schmitt, Thomas; Gupta, Rakesh; Lange, Stefan; Sonnenberger, Stefan; Dobner, Bodo; Hauß, Thomas; Rai, Beena; Neubert, Reinhard H H

    2018-05-30

    For this study mixtures based on the ceramides [NS] (NS = non-hydroxy-sphingosine) and [AP] (AP = α-hydroxy-phytosphingosine) in a 2:1 and 1:2 ratio, together with cholesterol and lignoceric acid, were investigated. These mixtures are modelling the uppermost skin layer, the stratum corneum. Neutron diffraction, utilizing specifically deuterated ceramide molecules, was used to obtain a maximum amount of experimental detail. Highly detailed molecular dynamics simulations were used to generate even more information from the experimental data. It was possible to observe a single lamellar phase for both systems. They had a lamellar repeat distance of 5.43 ± 0.05 nm for the [NS]/[AP] 2:1 and a slightly shorter one of 5.34 ± 0.05 nm for the 1:2 system. The structure and water content was uninfluenced by excess humidity. Both the experimental and simulation data indicated slightly tilted ceramides, with their C24 chains overlapping in the lamellar mid-plane. This arrangement is well comparable to systems investigated before. The structure of both systems, except for the differing repeat distance, looks similar at first. However, on a smaller scale there were various distinct differences, demonstrating only low redundancy between the different ceramide species, despite only minor chemical differences. The mainly ceramide [AP] determined 1:2 system has a slightly smaller repeat distance. This is a result of a tighter arrangement of the lipids chain along the bilayer normal and increased overlapping of the long chains in the lamellar middle. For the CER[NS] some novel features could be shown, despite it being the overall most investigated ceramide. These include the low adaptability to changed lateral interactions, leading to an increased chain opening. This effect could explain its low miscibility with other lipids. The investigated model systems allows it to directly compare results from the literature which have used ceramide [NS] to the most recent

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

    Science.gov (United States)

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

    2017-07-01

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

  3. In vivo confocal Raman microscopic determination of depth profiles of the stratum corneum lipid organization influenced by application of various oils.

    Science.gov (United States)

    Choe, ChunSik; Schleusener, Johannes; Lademann, Jürgen; Darvin, Maxim E

    2017-08-01

    The intercellular lipids (ICL) of stratum corneum (SC) play an important role in maintaining the skin barrier function. The lateral and lamellar packing order of ICL in SC is not homogenous, but rather depth-dependent. This study aimed to analyze the influence of the topically applied mineral-derived (paraffin and petrolatum) and plant-derived (almond oil and jojoba oil) oils on the depth-dependent ICL profile ordering of the SC in vivo. Confocal Raman microscopy (CRM), a unique tool to analyze the depth profile of the ICL structure non-invasively, is employed to investigate the interaction between oils and human SC in vivo. The results show that the response of SC to oils' permeation varies in the depths. All oils remain in the upper layers of the SC (0-20% of SC thickness) and show predominated differences of ICL ordering from intact skin. In these depths, skin treated with plant-derived oils shows more disordered lateral and lamellar packing order of ICL than intact skin (p0.1), except plant-derived oils at the depth 30% of SC thickness. In the deeper layers of the SC (60-100% of SC thickness), no difference between ICL lateral packing order of the oil-treated and intact skin can be observed, except that at the depths of 70-90% of the SC thickness, where slight changes with more disorder states are measured for plant-derived oil treated skin (p<0.1), which could be explained by the penetration of free fatty acid fractions in the deep-located SC areas. Both oil types remain in the superficial layers of the SC (0-20% of the SC thickness). Skin treated with mineral- and plant-derived oils shows significantly higher disordered lateral and lamellar packing order of ICL in these layers of the SC compared to intact skin. Plant-derived oils significantly changed the ICL ordering in the depths of 30% and 70-90% of the SC thickness, which is likely due to the penetration of free fatty acids in the deeper layers of the SC. Copyright © 2017 Japanese Society for

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

    Directory of Open Access Journals (Sweden)

    Tongcheng Dai

    2018-03-01

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

  5. The effect of chain length and lipid phase transitions on the selective permeability properties of liposomes

    NARCIS (Netherlands)

    Blok, M.C.; Neut-Kok, E.C.M. van der; Deenen, L.L.M. van; Gier, J. de

    1975-01-01

    This paper describes experiments showing the importance of the fatty acid chain length on the barrier properties of liposomal bilayers, prepared from saturated lecithins, under conditions of lateral phase separation. 1. 1.|Above the gel to liquid crystalline phase transition temperature,

  6. Alteration in lipid composition of plasma membranes of sensitive and resistant Guerin carcinoma cells due to the action of free and liposomal form of cisplatin.

    Science.gov (United States)

    Naleskina, L A; Todor, I N; Nosko, M M; Lukianova, N Y; Pivnyuk, V M; Chekhun, V F

    2013-09-01

    To study in vivo changes of lipid composition of plasma membranes of sensitive and resistant to cisplatin Guerin carcinoma cells under influence of free and liposomal cisplatin forms. The isolation of plasma membranes from parental (sensitive) and resistant to cisplatin Guerin carcinoma cells was by differential ultracentrifugation in sucrose density gradient. Lipids were detected by method of thin-layer chromatography. It was determined that more effective action of cisplatin liposomal form on resistant cells is associated with essential abnormalities of conformation of plasma membrane due to change of lipid components and architectonics of rafts. It results in the increase of membrane fluidity. Reconstructions in lipid composition of plasma membranes of cisplatin-resistant Guerin carcinoma cells provide more intensive delivery of drug into the cells, increase of its concentration and more effective interaction with cellular structural elements.

  7. Modeling cell membrane transport: interaction of guanidinylated poly(propylene imine) dendrimers with a liposomal membrane consisting of phosphate-based lipids.

    Science.gov (United States)

    Tsogas, Ioannis; Tsiourvas, Dimitris; Nounesis, George; Paleos, Constantinos M

    2006-12-19

    Mixed anionic liposomes consisting of dihexadecyl phosphate, phosphatidylcholine, and cholesterol were employed as model systems for assessing the ability of a series of functionalized dendrimers, bearing a varying number of guanidinium groups at their surface, to translocate across the liposomal bilayers. At low guanidinium/phosphate molar ratios or when weakly guanidinylated dendrimeric derivatives were employed, the dendrimeric derivative acted as a kind of "molecular glue" leading to a simple adhesion of the liposomes. Liposomal fusion occurred to a certain extent at high guanidinium/phosphate molar ratios or when highly guanidinylated dendrimeric derivatives were employed. Furthermore, translocation of these dendrimeric derivatives to the liposomal core was observed for low to medium guanidinylation and at low guanidinium/phosphate molar ratios which was, however, enhanced when the lipid bilayer was in its fluid liquid-crystalline phase. Thus, an optimum balance is required between the binding strength of guanidinium with the phosphate groups and the degree of hydrophilicity of the guanidinylated dendrimers for the transport of the latter to the liposomal core to occur.

  8. Liposomes, lipid nanocapsules and smartCrystals®: A comparative study for an effective quercetin delivery to the skin.

    Science.gov (United States)

    Hatahet, T; Morille, M; Hommoss, A; Devoisselle, J M; Müller, R H; Bégu, S

    2018-05-05

    Quercetin is a flavonoid with strong antioxidant and antiinflammatory activities considered as a potential drug candidate for skin exogenous supplementation. Nevertheless, crude quercetin suffers from poor water solubility and consequently topical inactivity. Therefore, quercetin formulation within a suitable system that overcomes its solubility limitation is a matter of investigation. Three approaches were tested to improve quercetin delivery to skin: liposomes, lipid nanocapsules (LNC) and smartCrystals®. These nanoformulations were compared in terms of average particle size, homogeneity (PDI), quercetin loading and cellular interactions with HaCaT (keratinocytes) and TPH-1 (monocytes) cell lines. Finally, two formulations were selected for testing quercetin delivery to human skin in vivo using stripping test. Different size distribution was obtained with each strategy starting from 26 nm with quercetin LNC, 179 nm with liposomes to 295 nm with quercetin smartCrystals®. The drug loading varied with each formulation from 0.56 mg/ml with liposomes, 10.8 mg/ml with LNC to 14.4 mg/ml with smartCrystals®. No toxicity was observed in HaCaT cells with quercetin and free radical scavenging ability was established at 5 µg/ml. The safety of quercetin at 5 µg/ml was further confirmed on THP-1 cells with efficient free radical scavenging ability. Finally, skin penetration evidenced different behavior between the two selected forms (LNC and SmartCrystals®), which could lead to different promising strategies for skin protection. On one side, quercetin smartCrystals® seems to enable the superficial deposition of quercetin on top of the skin, which presents a good strategy for a quercetin-based sunscreen product. On the other side, LNC seems to allow quercetin delivery to viable epidermis that holds the promise for skin inflammatory disorders such as psoriasis. Copyright © 2018. Published by Elsevier B.V.

  9. The preparation of functional lipid liposomes by γ-ray irradiation and its application

    International Nuclear Information System (INIS)

    Hosoi, Fumio; Akama, Kazuhiro.

    1997-01-01

    Encapsulation of the erythrocyte with polymerized phospholipid might improve the conventional erythrocyte preparations and liposome-encapsulated preparation. Therefore, production of an artificial erythrocyte was attempted using polymeric phospholipid. The behaviors of polymerization for several polymeric phospholipids following γ-ray irradiation were briefly described and the previous reports on the liposome polymerization was reviewed. In addition, the membranes thus obtained were characterized by kinetic assays and LB-membrane procedures in regards to the arrangement of membrane molecules and the interactions among hydrophobic groups in the domain. The polymerization of 1,2-bis-(2,4-octadecadienoyl)-sn-glycero-3-phosphocholine (DODPC) by γ-ray radiation was found superior to that by UV-radiation method. Since the generation of polymerization initiating molecule was not dependent on reaction temperature, it was possible to perform the polymerization at a low temperature, resulting that the heat denaturation of bioactive substances included into the liposome and also their leaks could be greatly repressed. (M.N.)

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

    International Nuclear Information System (INIS)

    Arshad, N.

    2013-01-01

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

  11. Mismatch discrimination of lipidated DNA and LNA-probes (LiNAs) in hybridization-controlled liposome assembly

    DEFF Research Database (Denmark)

    Jakobsen, Ulla; Vogel, Stefan

    2016-01-01

    Assays for mismatch discrimination and detection of single nucleotide variations by hybridization-controlled assembly of liposomes, which do not require tedious surface chemistry, are versatile for both DNA and RNA targets. We report herein a comprehensive study on different DNA and LNA (locked...... assay in the context of mismatch discrimination and SNP detection are presented. The advantages of membrane-anchored LiNA-probes compared to chemically attached probes on solid nanoparticles (e.g. gold nanoparticles) are described. Key functionalities such as non-covalent attachment of LiNA probes...... without the need for long spacers and the inherent mobility of membrane-anchored probes in lipid-bilayer membranes will be described for several different probe designs....

  12. Lipid raft-like liposomes used for targeted delivery of a chimeric entry-inhibitor peptide with anti-HIV-1 activity.

    Science.gov (United States)

    Gómara, María José; Pérez-Pomeda, Ignacio; Gatell, José María; Sánchez-Merino, Victor; Yuste, Eloisa; Haro, Isabel

    2017-02-01

    The work reports the design and synthesis of a chimeric peptide that is composed of the peptide sequences of two entry inhibitors which target different sites of HIV-1 gp41. The chimeric peptide offers the advantage of targeting two gp41 regions simultaneously: the fusion peptide and the loop both of which are membrane active and participate in the membrane fusion process. We therefore use lipid raft-like liposomes as a tool to specifically direct the chimeric inhibitor peptide to the membrane domains where the HIV-1 envelope protein is located. Moreover, the liposomes that mimic the viral membrane composition protect the chimeric peptide against proteolytic digestion thereby increasing the stability of the peptide. The described liposome preparations are suitable nanosystems for managing hydrophobic entry-inhibitor peptides as putative therapeutics. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. An isocratic HPLC method for the simultaneous determination of cholesterol, cardiolipin, and DOPC in lyophilized lipids and liposomal formulations.

    Science.gov (United States)

    Simonzadeh, Ninus

    2009-04-01

    Phospholipids, such as 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and 1,1',2,2'-tetramyristoyl cardiolipin, along with cholesterol, form liposomes in aqueous media and have been investigated at NeoPharm (Lake Bluff, IL) as drug-delivery systems. To accurately assess the effectiveness of various formulations involving the use of aforementioned phospholipids and cholesterol, their quantitative determination is essential. An isocratic high-performance liquid chromatographic method for the simultaneous determination of cholesterol, cardiolipin, and DOPC in various pharmaceutical formulations containing the active drug substance has consequently been developed and is presented here. The current method utilizes an ASTEC-diol analytical column and is shown to be stability-indicating and free from interference from any of the formulation excipients, such as sucrose, sodium chloride, and sodium lactate. The analytes are detected using an evaporative light scattering detector (Alltech or Polymer Laboratories). The quantitation of each lipid component is performed using non-linear regression analysis. The retention characteristics of the analytes are examined as a function of eluent composition (e.g., pH, salt content, organic to aqueous phase ratio) and column temperature. The method was validated and was found to be sensitive, specific, rugged, and cost-effective. The current method provides enhanced chromatographic separation for lipid components as well as degradation products as compared to similar methods reported in the literature. It is also inherently simpler than other similar methods reported in the literature that typically use complex gradient elution.

  14. Interaction of lipid nanoparticles with human epidermis and an organotypic cell culture model

    DEFF Research Database (Denmark)

    Kuntsche, Judith; Bunjes, Heike; Fahr, Alfred

    2008-01-01

    Various lipid nanoparticle formulations were investigated with respect to (trans)dermal drug delivery with special regard to the mechanism of their effects on human and an organotypic cell culture epidermis. Potential alterations of stratum corneum lipid domains were studied using fluorescence...... assays with labeled liposomes and thermal analysis of isolated stratum corneum. Influences on the permeation of corticosterone were investigated and the occlusive properties of the nanoparticles were determined by measurements of the transepidermal water loss (TEWL). The penetration of a fluorescence dye...... studies and thermal analysis of human and cell culture epidermis indicate that surface lipids, which are not present to the same extent in the cell culture model than in human epidermis, seem to play an important role....

  15. Characterization and In Vitro Skin Permeation of Meloxicam-Loaded Liposomes versus Transfersomes

    Directory of Open Access Journals (Sweden)

    Sureewan Duangjit

    2011-01-01

    Full Text Available The goal of this study was to develop and evaluate the potential use of liposome and transfersome vesicles in the transdermal drug delivery of meloxicam (MX. MX-loaded vesicles were prepared and evaluated for particle size, zeta potential, entrapment efficiency (%EE, loading efficiency, stability, and in vitro skin permeation. The vesicles were spherical in structure, 90 to 140 nm in size, and negatively charged (−23 to −43 mV. The %EE of MX in the vesicles ranged from 40 to 70%. Transfersomes provided a significantly higher skin permeation of MX compared to liposomes. Fourier Transform Infrared Spectroscopy (FT-IR and Differential Scanning Calorimetry (DSC analysis indicated that the application of transfersomes significantly disrupted the stratum corneum lipid. Our research suggests that MX-loaded transfersomes can be potentially used as a transdermal drug delivery system.

  16. Beyond liposomes: Recent advances on lipid based nanostructures for poorly soluble/poorly permeable drug delivery.

    Science.gov (United States)

    Teixeira, M C; Carbone, C; Souto, E B

    2017-10-01

    Solid lipid nanoparticle (SLN), nanostructured lipid carriers (NLC) and hybrid nanoparticles, have gained increasing interest as drug delivery systems because of their potential to load and release drugs from the Biopharmaceutical classification system (BCS) of class II (low solubility and high permeability) and of class IV (low solubility and low permeability). Lipid properties (e.g. high solubilizing potential, biocompatibility, biotolerability, biodegradability and distinct route of absorption) contribute for the improvement of the bioavailability of these drugs for a set of administration routes. Their interest continues to grow, as translated by the number of patents being field worldwide. This paper discusses the recent advances on the use of SLN, NLC and lipid-polymer hybrid nanoparticles for the loading of lipophilic, poorly water-soluble and poorly permeable drugs, being developed for oral, topical, parenteral and ocular administration, also discussing the industrial applications of these systems. A review of the patents filled between 2014 and 2017, concerning the original inventions of lipid nanocarriers, is also provided. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Czech Academy of Sciences Publication Activity Database

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

    2016-01-01

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

  18. Functional liposomes and supported lipid bilayers: towards the complexity of biological archetypes.

    Science.gov (United States)

    Berti, Debora; Caminati, Gabriella; Baglioni, Piero

    2011-05-21

    This perspective paper provides some illustrative examples on the interplay between information gathered on planar supported lipid bilayers (SLB) and unilamellar lipid vesicles (ULV) to get an integrated description of phenomena occurring at the nanoscale that involve locally bilayered structures. Similarities and differences are underlined and critically compared in terms of biomimetic fidelity and instrumental accessibility to structural and dynamical parameters, focusing on some recent reports that either explicitly address this comparison or introducing some studies that separately investigate the same process in SLB and lipid vesicles. Despite the structural similarity on the nanoscale, the different topology implies radically different characterization techniques that have evolved in sectorial and separated approaches. The quest for increasing levels of compositional complexity for bilayered systems should not result in a loss of structural and dynamical control: this is the central challenge of future research in this area, where the integrated approach highlighted in this contribution would enable improved levels of understanding. © The Owner Societies 2011

  19. Efficient transfection of Xenobiotic Responsive Element-biosensor plasmid using diether lipid and phosphatidylcholine liposomes in differentiated HepaRG cells.

    Science.gov (United States)

    Demazeau, Maxime; Quesnot, Nicolas; Ripoche, Nicolas; Rauch, Claudine; Jeftić, Jelena; Morel, Fabrice; Gauffre, Fabienne; Benvegnu, Thierry; Loyer, Pascal

    2017-05-30

    In this study, we evaluated cationic liposomes prepared from diether-NH 2 and egg phosphatidylcholine (EPC) for in vitro gene delivery. The impact of the lipid composition, i.e. the EPC and Diether-NH 2 molar ratio, on in vitro transfection efficiency and cytotoxicity was investigated using the human HEK293T and hepatoma HepaRG cells known to be permissive and poorly permissive cells for liposome-mediated gene transfer, respectively. Here, we report that EPC/Diether-NH 2 -based liposomes enabled a very efficient transfection with low cytotoxicity compared to commercial transfection reagents in both HEK293T and proliferating progenitor HepaRG cells. Taking advantage of these non-toxic EPC/Diether-NH 2 -based liposomes, we developed a method to efficiently transfect differentiated hepatocyte-like HepaRG cells and a biosensor plasmid containing a Xenobiotic Responsive Element and a minimal promoter driving the transcription of the luciferase reporter gene. We demonstrated that the luciferase activity was induced by a canonical inducer of cytochrome P450 genes, the benzo[a]pyrene, and two environmental contaminants, the fluoranthene, a polycyclic aromatic hydrocarbon, and the endosulfan, an organochlorine insecticide, known to induce toxicity and genotoxicity in differentiated HepaRG cells. In conclusion, we established a new efficient lipofection-mediated gene transfer in hepatocyte-like HepaRG cells opening new perspectives in drug evaluation relying on xenobiotic inducible biosensor plasmids. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Ashley R Long

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

  1. The density of GM1-enriched lipid rafts correlates inversely with the efficiency of transfection mediated by cationic liposomes.

    Science.gov (United States)

    Kovács, Tamás; Kárász, Andrea; Szöllosi, János; Nagy, Peter

    2009-08-01

    Although cationic liposome-mediated transfection has become a standard procedure, the mechanistic details of the process are unknown. It has been suggested that endocytic uptake of lipoplexes is efficient, and transfectability is largely determined by later steps. In this article, we stained GM1-enriched membrane microdomains, a subclass of lipid rafts, with subunit B of cholera toxin and correlated transfection efficiency with their density by quantitatively evaluating microscopic images. We found a strong anticorrelation between the density of GM1-enriched membrane microdomains and the efficacy of transfection monitored by measuring the expression level of GFP in different cell lines transfected by lipofection using two different transfection agents. These findings imply that GM1-enriched membrane microdomains interfere with the process of lipofection. The blocked step must be endocytosis since the accumulation of fluorescently labeled plasmids was lower in cells with high content of GM1-enriched membrane microdomains. Such a correlation was not observed in cells transfected by electroporation. By comparing the efficiency of lipofection in several cell lines we found that those with a high density of GM1-enriched membrane microdomains were the most resistant to transfection. We conclude that the inhibition of lipofection by GM1-enriched membrane microdomains is a general rule, and that endocytosis of lipoplexes can be rate limiting in cells with high density of GM1-enriched membrane rafts. Copyright 2009 International Society for Advancement of Cytometry.

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

    NARCIS (Netherlands)

    Gould, R.M.; London, Y.

    1972-01-01

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

  3. Impact of the long chain omega-acylceramides on the stratum corneum lipid nanostructure. Part 1: Thermotropic phase behaviour of CER[EOS] and CER[EOP] studied using X-ray powder diffraction and FT-Raman spectroscopy.

    Science.gov (United States)

    Kessner, Doreen; Brezesinski, Gerald; Funari, Sergio S; Dobner, Bodo; Neubert, Reinhard H H

    2010-01-01

    The stratum corneum (SC), the outermost layer of the mammalian skin, is the main skin barrier. Ceramides (CERs) as the major constituent of the SC lipid matrix are of particular interest. At the moment, 11 classes of CERs are identified, but the effect of each single ceramide species is still not known. Therefore in this article, the thermotropic behaviour of the long chain omega-acylceramides CER[EOS] and CER[EOP] was studied using X-ray powder diffraction and FT-Raman spectroscopy. It was found that the omega-acylceramides CER[EOS] and CER[EOP] do not show a pronounced polymorphism which is observed for shorter chain ceramides as a significant feature. The phase behaviour of both ceramides is strongly influenced by the extremely long acyl-chain residue. The latter has a much stronger influence compared with the structure of the polar head group, which is discussed as extremely important for the appearance of a rich polymorphism. Despite the strong influence of the long chain, the additional OH-group of the phyto-sphingosine type CER[EOP] influences the lamellar repeat distance and the chain packing. The less polar sphingosine type CER[EOS] is stronger influenced by the long acyl-chain residue. Hydration is necessary for the formation of an extended hydrogen-bonding network between the polar head groups leading to the appearance of a long-periodicity phase (LPP). In contrast, the more polar CER[EOP] forms the LPP with densely packed alkyl chains already in the dry state.

  4. The use of a new radioactive-iodine labeled lipid marker to follow in vivo disposition of liposomes: comparison with an encapsulated aqueous space marker

    International Nuclear Information System (INIS)

    Abra, R.M.; Schreier, H.; Szoka, F.C.

    1982-01-01

    The in vivo disposition of multilamellar liposomes extruded at 0.6 micrometers (PC/DPPA/CH/ alpha-T . 4:1:5:0.1 molar ratio) when injected i.v. into mice has been examined utilizing a novel iodinatable phospholipid derivative as a lipid phase marker (p-hydroxybenzamidine phosphatidylethanolamine: 125 I-BPE) and compared to that using 14 C-inulin as an aqueous phase marker. At times up to 5 h post-dose the disposition of both markers was essentially identical with the exception of blood and intestine, where 125 I-BPE levels were consistently higher than 14 C-inulin levels. At time intervals from 5-72 h post-dose 125 I-BPE levels in all the organs examined were lower than those of 14 C-inulin. These differences in the behaviour of the two labels may be explained in terms of exchange of the iodinated lipids, excretion of released inulin and long term metabolism of the lipid marker. We conclude tha 125 I-BPE is a useful marker for following liposome disposition in short-term studies particularly in view of the easily quantifiable nature of gamma-radioactivity which obviates the need for sample preparation

  5. Liposomes as carriers of imaging agents

    International Nuclear Information System (INIS)

    Caride, V.J.

    1985-01-01

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

  6. Lipid-protein nanodiscs for cell-free production of integral membrane proteins in a soluble and folded state: comparison with detergent micelles, bicelles and liposomes.

    Science.gov (United States)

    Lyukmanova, E N; Shenkarev, Z O; Khabibullina, N F; Kopeina, G S; Shulepko, M A; Paramonov, A S; Mineev, K S; Tikhonov, R V; Shingarova, L N; Petrovskaya, L E; Dolgikh, D A; Arseniev, A S; Kirpichnikov, M P

    2012-03-01

    Production of integral membrane proteins (IMPs) in a folded state is a key prerequisite for their functional and structural studies. In cell-free (CF) expression systems membrane mimicking components could be added to the reaction mixture that promotes IMP production in a soluble form. Here lipid-protein nanodiscs (LPNs) of different lipid compositions (DMPC, DMPG, POPC, POPC/DOPG) have been compared with classical membrane mimicking media such as detergent micelles, lipid/detergent bicelles and liposomes by their ability to support CF synthesis of IMPs in a folded and soluble state. Three model membrane proteins of different topology were used: homodimeric transmembrane (TM) domain of human receptor tyrosine kinase ErbB3 (TM-ErbB3, 1TM); voltage-sensing domain of K(+) channel KvAP (VSD, 4TM); and bacteriorhodopsin from Exiguobacterium sibiricum (ESR, 7TM). Structural and/or functional properties of the synthesized proteins were analyzed. LPNs significantly enhanced synthesis of the IMPs in a soluble form regardless of the lipid composition. A partial disintegration of LPNs composed of unsaturated lipids was observed upon co-translational IMP incorporation. Contrary to detergents the nanodiscs resulted in the synthesis of ~80% active ESR and promoted correct folding of the TM-ErbB3. None of the tested membrane mimetics supported CF synthesis of correctly folded VSD, and the protocol of the domain refolding was developed. The use of LPNs appears to be the most promising approach to CF production of IMPs in a folded state. NMR analysis of (15)N-Ile-TM-ErbB3 co-translationally incorporated into LPNs shows the great prospects of this membrane mimetics for structural studies of IMPs produced by CF systems. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Reconstitution of proapoptotic BAK function in liposomes reveals a dual role for mitochondrial lipids in the BAK-driven membrane permeabilization process.

    Science.gov (United States)

    Landeta, Olatz; Landajuela, Ane; Gil, David; Taneva, Stefka; Di Primo, Carmelo; Sot, Begoña; Valle, Mikel; Frolov, Vadim A; Basañez, Gorka

    2011-03-11

    BAK is a key effector of mitochondrial outer membrane permeabilization (MOMP) whose molecular mechanism of action remains to be fully dissected in intact cells, mainly due to the inherent complexity of the intracellular apoptotic machinery. Here we show that the core features of the BAK-driven MOMP pathway can be reproduced in a highly simplified in vitro system consisting of recombinant human BAK lacking the carboxyl-terminal 21 residues (BAKΔC) and tBID in combination with liposomes bearing an appropriate lipid environment. Using this minimalist reconstituted system we established that tBID suffices to trigger BAKΔC membrane insertion, oligomerization, and pore formation. Furthermore, we demonstrate that tBID-activated BAKΔC permeabilizes the membrane by forming structurally dynamic pores rather than a large proteinaceous channel of fixed size. We also identified two distinct roles played by mitochondrial lipids along the molecular pathway of BAKΔC-induced membrane permeabilization. First, using several independent approaches, we showed that cardiolipin directly interacts with BAKΔC, leading to a localized structural rearrangement in the protein that "primes" BAKΔC for interaction with tBID. Second, we provide evidence that selected curvature-inducing lipids present in mitochondrial membranes specifically modulate the energetic expenditure required to create the BAKΔC pore. Collectively, our results support the notion that BAK functions as a direct effector of MOMP akin to BAX and also adds significantly to the growing evidence indicating that mitochondrial membrane lipids are actively implicated in BCL-2 protein family function.

  8. Effectiveness of Sunscreen at Preventing Solar UV-Induced Alterations of Human Stratum Corneum

    Science.gov (United States)

    Martinez, O.; Dauskardt, R.; Biniek, K.; Novoa, F.

    2012-12-01

    The outermost layer of the epidermis, the stratum corneum, protects the body from harmful environmental conditions by serving as a selective barrier. Solar ultraviolet (UV) radiation is one of the most common conditions the body encounters and is responsible for many negative skin responses, including compromised barrier function. UV exposure has dramatic effects on stratum corneum cell cohesion and mechanical integrity that are related to its effects on the stratum corneum's intercellular lipids. Hypothesis Sunscreen contains chemicals that absorb UV radiation to prevent the radiation from penetrating the skin. Thus, it is expected that the application of sunscreen on human stratum corneum will reduce UV-induced alterations of human stratum corneum. Procedures/Equipment Human tissue was processed in order to isolate the stratum corneum, the top layer of the epidermis. Double cantilever beam (DCB) testing was used to study the effect of UV radiation on human stratum corneum. Two different types of DCB samples were created: control DCB samples with the application of carrier and UV light to the stratum corneum and DCB samples with the application of sunscreen and UV light to the stratum corneum. For the control sample, one side of the stratum corneum was glued to a polycarbonate beam and carrier was applied. Then, the sample was placed 10 cm away from the UV lamp inside of the environmental chamber and were exposed to UV dosages of about 800 J/cm2. Once this step was complete, a second polycarbonate beam was glued to the other side of the stratum corneum. The steps were similar for the DCB sample that had sunscreen applied and that was exposed to UV light. After gluing one side of the stratum corneum to a polycarbonate beam, Octinoxate sunscreen was applied. The next steps were similar to those of the control sample. All DCB samples were then let out to dry for two hours in a dry box in order for the moisture from the lab to be extracted. Each DCB sample was tested

  9. Optimization of Liposomal Lipid Composition for a New, Reactive Sulfur Donor, and In Vivo Efficacy Studies on Mice to Antagonize Cyanide Intoxication

    Directory of Open Access Journals (Sweden)

    Ilona Petrikovics

    2011-01-01

    Full Text Available Present studies have focused on a novel cyanide antidotal system, on the coencapsulation of a new sulfur donor DTO with rhodanese within sterically stabilized liposomes. The optimal lipid composition for coencapsulation of DTO with rhodanese is the combination of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, cholesterol, cationic lipid (DOTAP, and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol-2000] ammonium salt (with molar ratios of 82.7 : 9.2 : 3.0 : 5.1. With the optimized compositions, prophylactic and therapeutic in vivo efficacy studies were carried out in a mice model. When DTO was coencapsulated with rhodanese and thiosulfate the prophylactic antidotal protection was 4.9×LD50. Maximum antidotal protection against cyanide intoxication (15×LD50 was achieved with coencapsulated rhodanese and DTO/thiosulfate in combination with sodium nitrite. When applied therapeutically, 100% survival rate (6/6 was achieved at 20 mg/kg cyanide doses with the encapsulated DTO-rhodanese-thiosulfate antidotal systems with and without sodium nitrite. These data are indicating that the appropriately formulated DTO is a promising sulfur donor for cyanide antagonism.

  10. Liposomes containing monophosphoryl lipid A and QS-21 serve as an effective adjuvant for soluble circumsporozoite protein malaria vaccine FMP013.

    Science.gov (United States)

    Genito, Christopher J; Beck, Zoltan; Phares, Timothy W; Kalle, Fanta; Limbach, Keith J; Stefaniak, Maureen E; Patterson, Noelle B; Bergmann-Leitner, Elke S; Waters, Norman C; Matyas, Gary R; Alving, Carl R; Dutta, Sheetij

    2017-07-05

    Malaria caused by Plasmodium falciparum continues to threaten millions of people living in the tropical parts of the world. A vaccine that confers sterile and life-long protection remains elusive despite more than 30years of effort and resources invested in solving this problem. Antibodies to a malaria vaccine candidate circumsporozoite protein (CSP) can block invasion and can protect humans against malaria. We have manufactured the Falciparum Malaria Protein-013 (FMP013) vaccine based on the nearly full-length P. falciparum CSP 3D7 strain sequence. We report here immunogenicity and challenge data on FMP013 antigen in C57BL/6 mice formulated with two novel adjuvants of the Army Liposome Formulation (ALF) series and a commercially available adjuvant Montanide ISA 720 (Montanide) as a control. ALF is a liposomal adjuvant containing a synthetic monophosphoryl lipid A (3D-PHAD®). In our study, FMP013 was adjuvanted with ALF alone, ALF containing aluminum hydroxide (ALFA) or ALF containing QS-21 (ALFQ). Adjuvants ALF and ALFA induced similar antibody titers and protection against transgenic parasite challenge that were comparable to Montanide. ALFQ was superior to the other three adjuvants as it induced higher antibody titers with improved boosting after the third immunization, higher serum IgG2c titers, and enhanced protection. FMP013+ALFQ also augmented the numbers of splenic germinal center-derived activated B-cells and antibody secreting cells compared to Montanide. Further, FMP013+ALFQ induced antigen-specific IFN-γ ELISPOT activity, CD4 + T-cells and a T H 1-biased cytokine profile. These results demonstrate that soluble CSP can induce a potent and sterile protective immune response when formulated with the QS-21 containing adjuvant ALFQ. Comparative mouse immunogenicity data presented here were used as the progression criteria for an ongoing non-human primate study and a regulatory toxicology study in preparation for a controlled human malaria infection (CHMI

  11. 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

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

    Science.gov (United States)

    Spelios, Michael G.

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

  13. Convenient synthesis and application of versatile nucleic acid lipid membrane anchors in the assembly and fusion of liposomes

    DEFF Research Database (Denmark)

    Ries, Oliver; Löffler, Philipp M. G.; Vogel, Stefan

    2015-01-01

    or the construction of DNA origami structures. We herein present the synthesis and applications of versatile lipid membrane anchor building blocks suitable for solid phase oligonucleotide synthesis. These are readily synthesized in bulk in five to seven steps from commercially available precursors and can...

  14. 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.

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

    Science.gov (United States)

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

    2008-01-01

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

  16. Liposome kinetics in infarcted canine myocardium

    International Nuclear Information System (INIS)

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

    1984-01-01

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

  17. 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.

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

    Science.gov (United States)

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

    2018-02-13

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

  19. Physico-chemical studies on the interaction of dendrimers with lipid bilayers. 1. Effect of dendrimer generation and liposome surface charge.

    Science.gov (United States)

    Roy, Biplab; Panda, Amiya Kumar; Parimi, Srinivas; Ametov, Igor; Barnes, Timothy; Prestidge, Clive A

    2014-01-01

    Studies on the interaction of different generation poly (amido amine) (PAMAM) dendrimers (2G, 4G and 6G) and liposomes of different compositions were carried out by a combined turbidity, dynamic light scattering and atomic force microscopic measurements. Liposomes comprising soy lecithin (SLC, negative surface charge), 1, 2-palmitoyl-sn-glycero-3-phosphatidylcholine (DPPC, mildly positive surface charge), 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol (DPPG, negatively charged) and a biologically simulated mixture of DPPC + DPPG (7:3, M/M, negatively charged) were used as model bilayers. 30 wt% cholesterol was used in each combination as it is known to control the fluidity of membrane bilayers. Silica was used as a negatively charged hard sphere model with an aim to compare the results. Both the turbidity and hydrodynamic diameter values of all the liposomes, except DPPC, passed through maxima upon the progressive addition of PAMAM; the effect was insignificant in case of DPPC. Formation of dendriosome, a complex formed between dendrimer and liposome, resulted in the charge reversal of the negatively charged liposomes. Interaction between PAMAM and liposome was found to be governed by electrostatic as well as hydrogen bonding. Generation dependent PAMAM activity followed the order: 6G >4G>2G in terms of overall dendrimer concentration. However, interestingly, the order was reverse when PAMAM activity was considered in terms of total end group concentrations. AFM studies reveal the rupture of bilayer structure upon addition of dendrimer.

  20. Turn-over of Stratijm Corneum in Leprosy

    Directory of Open Access Journals (Sweden)

    R P Okhandiar

    1987-01-01

    Full Text Available Stratum corneum showed increased proliferative activity on the patches of leprosy as evidenced by a significantly fast stratum corneum turnover time (p 0.001 measured by fluorescent staining technic with dansyl chloride. These findings suggest imperfect keratinization on the patches of leprosy leading to formation of structurally weak stratum corneum.

  1. Comparative SAXS and DSC study on stratum corneum structural organization in an epidermal cell culture model (ROC)

    DEFF Research Database (Denmark)

    Kuntsche, Judith; Herre, Angela; Fahr, Alfred

    2013-01-01

    barrier similar to that of human stratum corneum is, however, a prerequisite. In this study, the stratum corneum lipid organization in an epidermal cell culture model based on rat epidermal keratinocytes (REK organotypic culture, ROC) was investigated by small-angle X-ray scattering (SAXS) in dependence......Cell cultured skin equivalents present an alternative for dermatological in vitro evaluations of drugs and excipients as they provide the advantage of availability, lower variability and higher assay robustness compared to native skin. For penetration/permeation studies, an adequate stratum corneum...... and SC lipid organization. Cultivation for 21days resulted in further minor changes in the structural organization of ROC SC. The SAXS patterns of ROC SC had overall large similarities with that of human SC and point to the presence of a long periodicity phase with a repeat distance of about 122Å, e...

  2. Sampling the stratum corneum for toxic chemicals.

    Science.gov (United States)

    Coman, Garrett; Blickenstaff, Nicholas R; Blattner, Collin M; Andersen, Rosa; Maibach, Howard I

    2014-01-01

    Dermal exposure is an important pathway in environmental health. Exposure comes from contaminated water, soil, treated surfaces, textiles, aerosolized chemicals, and agricultural products. It can occur in homes, schools, play areas, and work settings in the form of industrial sources, consumer products, or hazardous wastes. Dermal exposure is most likely to occur through contact with liquids, water, soil, sediment, and contaminated surfaces. The ability to detect and measure exposure to toxic materials on the skin is an important environmental health issue. The stratum corneum is the skin's first and principal barrier layer of protection from the outside world. It has a complex structure that can effectively protect against a wide variety of physical, chemical, and biological contaminants. However, there are a variety of chemical agents that can damage the stratum corneum and the underlying epidermis, dermis and subcutis, and/or enter systemic circulation through the skin. There are numerous ways of sampling the stratum corneum for these toxic materials like abrasion techniques, biopsy, suction blistering, imaging, washing, wipe sampling, tape stripping, and spot testing. Selecting a method likely depends on the particular needs of the situation. Hence, there is a need to review practical considerations for their use in sampling the stratum corneum for toxins.

  3. Development and evaluation of resveratrol, Vitamin E, and epigallocatechin gallate loaded lipid nanoparticles for skin care applications.

    Science.gov (United States)

    Chen, Jin; Wei, Ning; Lopez-Garcia, Maria; Ambrose, Dianna; Lee, Jason; Annelin, Colin; Peterson, Teresa

    2017-08-01

    Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been studied as potential carriers for both dermal and transdermal drug delivery. SLN contain lipid droplets that are fully crystallized and have a highly-ordered crystalline structure. NLC are modified SLN in which the lipid phase contains both solid and liquid lipids at room temperature. SLN and NLC are thought to combine the advantages of polymeric particles, liposomes and emulsions. Therefore they provide high encapsulation percentages, better protection for incorporated actives and allow for control of desired release profile. In this work, Resveratrol, Vitamin E (VE), and Epigallocatechin Gallate (EGCG) all potent antioxidants known to provide protection to the skin, were formulated into lipid nanoparticles. Several different formulations were successfully developed and demonstrated high uniformity and stability. Both resveratrol and VE lipid nanoparticles provided effective protection of actives against UV induced degradation. However, lipid nanoparticles did not show protection from UV degradation for EGCG in this work. An active release study exhibited a sustained release of resveratrol over 70% after 24h. Skin penetration studies showed that lipid nanoparticles directionally improved the penetration of resveratrol through the stratum corneum. Our findings suggest that lipid nanoparticles are promising viable carriers for the delivery of resveratrol and VE to provide longlasting antioxidant benefits to the skin. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. 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...

  5. Pig skin structure and transdermal delivery of liposomes: a two photon microscopy study

    DEFF Research Database (Denmark)

    Carrer, Dolores C.; Vermehren, Charlotte; Bagatolli, Luis

    2008-01-01

    In this work we have characterized the architecture and physical properties of pig skin epidermis including its permeability to different liposome formulations. Autofluorescence images show that cells in the epidermis, from the basal layer to the stratum corneum, are organized in clusters that ar...

  6. Stratum corneum molecular mobility in the presence of natural moisturizers.

    Science.gov (United States)

    Björklund, Sebastian; Andersson, Jenny Marie; Pham, Quoc Dat; Nowacka, Agnieszka; Topgaard, Daniel; Sparr, Emma

    2014-07-07

    The outermost layer of the skin, the stratum corneum (SC), is a lipid-protein membrane that experiences considerable osmotic stress from a dry and cold climate. The natural moisturizing factor (NMF) comprises small and polar substances, which like osmolytes can protect living systems from osmotic stress. NMF is commonly claimed to increase the water content in the SC and thereby protect the skin from dryness. In this work we challenge this proposed mechanism, and explore the influence of NMF on the lipid and protein components in the SC. We employ natural-abundance (13)C solid-state NMR methods to investigate how the SC molecular components are influenced by urea, glycerol, pyrrolidone carboxylic acid (PCA), and urocanic acid (UCA), all of which are naturally present in the SC as NMF compounds. Experiments are performed with intact SC, isolated corneocytes and model lipids. The combination of NMR experiments provides molecularly resolved qualitative information on the dynamics of different SC lipid and protein components. We obtain completely novel molecular information on the interaction of these NMF compounds with the SC lipids and proteins. We show that urea and glycerol, which are also common ingredients in skin care products, increase the molecular mobility of both SC lipids and proteins at moderate relative humidity where the SC components are considerably more rigid in the absence of these compounds. This effect cannot be attributed to increased SC water content. PCA has no detectable effect on SC molecular mobility under the conditions investigated. It is finally shown that the more apolar compound, UCA, specifically influences the mobility of the SC lipid regions. The present results show that the NMF components act to retain the fluidity of the SC molecular components under dehydrating conditions in such a way that the SC properties remain largely unchanged as compared to more hydrated SC. These findings provide a new molecular insight into how small

  7. Mechanics, morphology, and mobility in stratum corneum membranes

    Science.gov (United States)

    Olmsted, Peter; Das, Chinmay; Noro, Massimo

    2012-02-01

    The stratum corneum is the outermost layer of skin, and serves as a protective barrier against external agents, and to control moisture. It comprises keratin bodies (corneocytes) embedded in a matrix of lipid bilayers. Unlike the more widely studied phospholipid bilayers, the SC bilayers are typically in a gel-like state. Moreover, the SC membrane composition is radically different from more fluid counterparts: it comprises single tailed fatty acids, ceramides, and cholesterol; with many distinct ceramides possessing different lengths of tails, and always with two tails of different lengths. I will present insight from computer simulations into the morphology, mechanical properties, and diffusion (barrier) properties of these highly heterogeneous membranes. Our results provide some clue as to the design principles for the SC membrane, and is an excellent example of the use of wide polydispersity by natural systems.

  8. 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.

  9. Multimodal targeted high relaxivity thermosensitive liposome for in vivo imaging

    Science.gov (United States)

    Kuijten, Maayke M. P.; Hannah Degeling, M.; Chen, John W.; Wojtkiewicz, Gregory; Waterman, Peter; Weissleder, Ralph; Azzi, Jamil; Nicolay, Klaas; Tannous, Bakhos A.

    2015-11-01

    Liposomes are spherical, self-closed structures formed by lipid bilayers that can encapsulate drugs and/or imaging agents in their hydrophilic core or within their membrane moiety, making them suitable delivery vehicles. We have synthesized a new liposome containing gadolinium-DOTA lipid bilayer, as a targeting multimodal molecular imaging agent for magnetic resonance and optical imaging. We showed that this liposome has a much higher molar relaxivities r1 and r2 compared to a more conventional liposome containing gadolinium-DTPA-BSA lipid. By incorporating both gadolinium and rhodamine in the lipid bilayer as well as biotin on its surface, we used this agent for multimodal imaging and targeting of tumors through the strong biotin-streptavidin interaction. Since this new liposome is thermosensitive, it can be used for ultrasound-mediated drug delivery at specific sites, such as tumors, and can be guided by magnetic resonance imaging.

  10. Dehydration of multilamellar fatty acid membranes: Towards a computational model of the stratum corneum

    Science.gov (United States)

    MacDermaid, Christopher M.; DeVane, Russell H.; Klein, Michael L.; Fiorin, Giacomo

    2014-12-01

    The level of hydration controls the cohesion between apposed lamellae of saturated free fatty acids found in the lipid matrix of stratum corneum, the outermost layer of mammalian skin. This multilamellar lipid matrix is highly impermeable to water and ions, so that the local hydration shell of its fatty acids may not always be in equilibrium with the acidity and relative humidity, which significantly change over a course of days during skin growth. The homeostasis of the stratum corneum at each moment of its growth likely requires a balance between two factors, which affect in opposite ways the diffusion of hydrophilic species through the stratum corneum: (i) an increase in water order as the lipid lamellae come in closer contact, and (ii) a decrease in water order as the fraction of charged fatty acids is lowered by pH. Herein molecular dynamics simulations are employed to estimate the impact of both effects on water molecules confined between lamellae of fatty acids. Under conditions where membrane undulations are energetically favorable, the charged fatty acids are able to sequester cations around points of contact between lamellae that are fully dehydrated, while essentially maintaining a multilamellar structure for the entire system. This observation suggests that the undulations of the fatty acid lamellae control the diffusion of hydrophilic species through the water phase by altering the positional and rotational order of water molecules in the embedded/occluded "droplets."

  11. 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.

  12. Vehicle effects on human stratum corneum absorption and skin penetration.

    Science.gov (United States)

    Zhang, Alissa; Jung, Eui-Chang; Zhu, Hanjiang; Zou, Ying; Hui, Xiaoying; Maibach, Howard

    2017-05-01

    This study evaluated the effects of three vehicles-ethanol (EtOH), isopropyl alcohol (IPA), and isopropyl myristate (IPM)-on stratum corneum (SC) absorption and diffusion of the [ 14 C]-model compounds benzoic acid and butenafine hydrochloride to better understand the transport pathways of chemicals passing through and resident in SC. Following application of topical formulations to human dermatomed skin for 30 min, penetration flux was observed for 24 h post dosing, using an in vitro flow-through skin diffusion system. Skin absorption and penetration was compared to the chemical-SC (intact, delipidized, or SC lipid film) binding levels. A significant vehicle effect was observed for chemical skin penetration and SC absorption. IPA resulted in the greatest levels of intact SC/SC lipid absorption, skin penetration, and total skin absorption/penetration of benzoic acid, followed by IPM and EtOH, respectively. For intact SC absorption and total skin absorption/penetration of butenafine, the vehicle that demonstrated the highest level of sorption/penetration was EtOH, followed by IPA and IPM, respectively. The percent doses of butenafine that were absorbed in SC lipid film and penetrated through skin in 24 h were greatest for IPA, followed by EtOH and IPM, respectively. The vehicle effect was consistent between intact SC absorption and total chemical skin absorption and penetration, as well as SC lipid absorption and chemical penetration through skin, suggesting intercellular transport as a main pathway of skin penetration for model chemicals. These results suggest the potential to predict vehicle effects on skin permeability with simple SC absorption assays. As decontamination was applied 30 min after chemical exposure, significant vehicle effects on chemical SC partitioning and percutaneous penetration also suggest that skin decontamination efficiency is vehicle dependent, and an effective decontamination method should act on chemical solutes in the lipid domain.

  13. 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.

  14. Novel liposomal technology applied in esophageal cancer treatment

    Science.gov (United States)

    Yeh, Chia-Hsien; Hsieh, Yei-San; Yang, Pei-wen; Huang, Leaf; Hsu, Yih-Chih

    2018-02-01

    Cisplatin (CDDP) has been commonly used as a chemotherapeutic drug, mainly used for the treatment of malignant epithelial cell tumors. We have developed a new method based on innovative lipid calcium phosphate, which encapsulated hydrophobic drugs to form liposomal nanoparticles. Esophageal cancer xenograft model was used to investigate the efficacy of liposomal nanoparticles. and it showed good therapeutic efficacy with lower side effects. Liposomal nanoparticles exhibited a better therapeutic effect than that of conventional CDDP.

  15. 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.

  16. Budget impact analysis of liposomal amphotericin B and amphotericin B lipid complex in the treatment of invasive fungal infections in the United States.

    Science.gov (United States)

    Yang, Hongbo; Chaudhari, Paresh; Zhou, Zheng-Yi; Wu, Eric Q; Patel, Chad; Horn, David L

    2014-02-01

    Liposomal amphotericin B (L-AMB) and amphotericin B lipid complex (ABLC) are both indicated for treating invasive fungal infections (IFIs) caused by Aspergillus, Candida and Cryptococcus spp. among patients who are refractory to or intolerant of conventional amphotericin B (CAB). Prior studies have suggested similar efficacies but differences in adverse event (AE) profiles between L-AMB and ABLC. Our objective was to conduct a cost-minimisation and budget impact analysis for the treatment of IFIs with L-AMB and ABLC in a US hospital setting. A Microsoft® Excel-based budget impact model was developed to estimate the costs associated with using L-AMB and ABLC for the treatment of adult patients with Aspergillus, Candida and Cryptococcus spp. infections, who are refractory to or intolerant of CAB, during a hospital stay. The model was built from a hospital perspective, and included drug costs of L-AMB and ABLC, and costs for treating drug-related AEs (i.e. nephrotoxicity with/without dialysis, infusion-related reactions, anaphylaxis, hypomagnesaemia and hypokalaemia). Average sales price was used as the drug cost estimate in the base-case analyses. The treatment duration and rates of AEs for L-AMB and ABLC were mainly obtained from a retrospective study of these two drugs in the target population using the Cerner Health Facts data. Treatment costs of AEs were obtained from the publicly available sources. The budget impact ($US, year 2011 values) was evaluated for a hypothetical hospital with 100 administrations where L-AMB and ABLC are used for the treatment of the target population by changing the market share of L-AMB and ABLC from 32/68% to an anticipated market share of 60/40% in the base-case analysis. Sensitivity analyses were conducted by varying drug costs, rates of AEs, costs of AEs and anticipated market shares of L-AMB and ABLC. The estimated per-patient cost per hospital episode associated with L-AMB and ABLC use were $US14,563 and $US16,748, respectively

  17. Effect of vehicles and sodium lauryl sulphate on xenobiotic permeability and stratum corneum partitioning in porcine skin

    International Nuclear Information System (INIS)

    Merwe, Deon van der; Riviere, Jim E.

    2005-01-01

    Dermal contact with potentially toxic agricultural and industrial chemicals is a common hazard encountered in occupational, accidental spill and environmental contamination scenarios. Different solvents and chemical mixtures may influence dermal absorption. The effects of sodium lauryl sulphate (SLS) on the stratum corneum partitioning and permeability in porcine skin of 10 agricultural and industrial chemicals in water, ethanol and propylene glycol were investigated. The chemicals were phenol, p-nitrophenol, pentachlorophenol, methyl parathion, ethyl parathion, chlorpyrifos, fenthion, simazine, atrazine and propazine. SLS decreased partitioning into stratum corneum from water for lipophilic compounds, decreased partitioning from propylene glycol and did not alter partitioning from ethanol. SLS effects on permeability were less consistent, but generally decreased permeability from water, increased permeability from ethanol and had an inconsistent effect on permeability from propylene glycol. It was concluded that, for the compounds tested, partitioning into the stratum corneum was determined by the relative solubility of the solute in the donor solvent and the stratum corneum lipids. Permeability, however, reflected the result of successive, complex processes and was not predictable from stratum corneum partitioning alone. Addition of SLS to solvents altered partitioning and absorption characteristics across a range of compounds, which indicates that partition coefficients or skin permeability from neat chemical exposure should be used with caution in risk assessment procedures for chemical mixtures

  18. 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

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

    International Nuclear Information System (INIS)

    Hnatowich, D.J.; Clancy, B.

    1980-01-01

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

  20. 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.

  1. Effect of stratum corneum heterogeneity, anisotropy, asymmetry and follicular pathway on transdermal penetration.

    Science.gov (United States)

    Barbero, Ana M; Frasch, H Frederick

    2017-08-28

    The impact of the complex structure of the stratum corneum on transdermal penetration is not yet fully described by existing models. A quantitative and thorough study of skin permeation is essential for chemical exposure assessment and transdermal delivery of drugs. The objective of this study is to analyze the effects of heterogeneity, anisotropy, asymmetry, follicular diffusion, and location of the main barrier of diffusion on percutaneous permeation. In the current study, the solution of the transient diffusion through a two-dimensional-anisotropic brick-and-mortar geometry of the stratum corneum is obtained using the commercial finite element program COMSOL Multiphysics. First, analytical solutions of an equivalent multilayer geometry are used to determine whether the lipids or corneocytes constitute the main permeation barrier. Also these analytical solutions are applied for validations of the finite element solutions. Three illustrative compounds are analyzed in these sections: diethyl phthalate, caffeine and nicotine. Then, asymmetry with depth and follicular diffusion are studied using caffeine as an illustrative compound. The following findings are drawn from this study: the main permeation barrier is located in the lipid layers; the flux and lag time of diffusion through a brick-and-mortar geometry are almost identical to the values corresponding to a multilayer geometry; the flux and lag time are affected when the lipid transbilayer diffusivity or the partition coefficients vary with depth, but are not affected by depth-dependent corneocyte diffusivity; and the follicular contribution has significance for low transbilayer lipid diffusivity, especially when flux between the follicle and the surrounding stratum corneum is involved. This study demonstrates that the diffusion is primarily transcellular and the main barrier is located in the lipid layers. Published by Elsevier B.V.

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

    Science.gov (United States)

    Kohli, Aditya G.

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

  3. Fluorescence studies on gamma irradiated egg lecithin liposomal membrane

    International Nuclear Information System (INIS)

    Pandey, B.N.; Mishra, K.P.

    1998-01-01

    Alterations in structure and organization of sonicated EYL liposomal vesicular membrane after irradiation was investigated by DPH fluorescence probe which is a well known reporter for the environment of hydrophobic interior of membrane. Results of present study have demonstrated that loss of DPH fluorescence in liposomal membrane is linked to free radical mediated structural alterations possibly rigidization in the lipid bilayer

  4. Structural properties of liposomes from digital holographic microscopy

    Science.gov (United States)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2014-11-03

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

  6. 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.

  7. The role of cavitation in liposome formation.

    Science.gov (United States)

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

    2007-12-15

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

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

    Science.gov (United States)

    Schroeder, Avi; Kost, Joseph; Barenholz, Yechezkel

    2009-11-01

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

  9. 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...

  10. Photosensitization of liposomes by porphyrins

    Energy Technology Data Exchange (ETDEWEB)

    Grossweiner, L I; Goyal, G C

    1984-01-01

    Lipid peroxidation was photosensitized in egg phosphatidylcholine (EPC) liposomes by hematoporphyrin (HP), hematoporphyrin derivative (HpD) and uroporphyrin I (Uro-I). Photosensitization by HP was type II via singlet oxygen (/sup 1/O/sub 2/) for the monomeric and dimeric states and type I for aggregated HP. Uro-I was an efficient type II /sup 1/O/sub 2/ photosensitizer. The HpD fraction enriched in the active biological component (HpD-A) was a type II /sup 1/O/sub 2/ photosensitizer at high and low concentrations. The spectral differences between HpD-A in buffer and solubilized in small EPC liposomes are attributed to a conformation change of a key dimer constituent from a folded to a planar geometry. The implications of the results for the action mechanism in photoradiation therapy of tumors with these porphyrins are discussed. 73 references, 1 figure, 5 tables.

  11. Mechanical Division of Cell-Sized Liposomes

    NARCIS (Netherlands)

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

    2018-01-01

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

  12. Application of Gelidium corneum edible films containing carvacrol for ham packages.

    Science.gov (United States)

    Lim, G O; Hong, Y H; Song, K B

    2010-01-01

    We prepared an edible film of Gelidium corneum (GC) containing carvacrol as an antimicrobial and antioxidative agent. The GC film containing carvacrol significantly decreased the WVP, while TS and %E values were increased, compared to the film without carvacrol. Increasing amounts of an antimicrobial agent increased antimicrobial activity against Escherichia coli O157:H7 and Listeria monocytogenes. Application of the film to ham packaging successfully inhibited the microbial growth and lipid oxidation of ham during storage. Our results indicate that GC film can be a useful edible packaging material for food products, and the incorporation of carvacrol in the GC film may extend the shelf life.

  13. The impact of ultraviolet therapy on stratum corneum ceramides and barrier function

    DEFF Research Database (Denmark)

    Jungersted, Jakob Mutanu; Høgh, Julie Kaae; Hellgren, Lars

    2011-01-01

    therapy in dermatological patients on ceramides and skin barrier function.We found that UV light treatment does not change the ratio of important stratum corneum lipids, but we confirm earlier findings of decreased susceptibility to irritants after UV- therapy.......The ceramide profile as well as the barrier function is known to be deteriorated in atopic eczema and psoriasis, and ultraviolet (UV) light is known to improve the barrier function. The impact of UV light on ceramides, however, is not clarified.The aim of this study was to examine the effect of UV...

  14. The impact of ultraviolet therapy on stratum corneum ceramides and barrier function

    DEFF Research Database (Denmark)

    Jungersted, Jakob Mutanu; Høgh, Julie Kaae; Hellgren, Lars

    2011-01-01

    therapy in dermatological patients on ceramides and skin barrier function. We found that UV light treatment does not change the ratio of important stratum corneum lipids, but we confirm earlier findings of decreased susceptibility to irritants after UV- therapy.......The ceramide profile as well as the barrier function is known to be deteriorated in atopic eczema and psoriasis, and ultraviolet (UV) light is known to improve the barrier function. The impact of UV light on ceramides, however, is not clarified. The aim of this study was to examine the effect of UV...

  15. Silica-Coated Liposomes for Insulin Delivery

    OpenAIRE

    Neelam Dwivedi; M. A. Arunagirinathan; Somesh Sharma; Jayesh Bellare

    2010-01-01

    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 evid...

  16. Octanol-assisted liposome assembly on chip

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2017-08-01

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

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

    DEFF Research Database (Denmark)

    Parmentier, Johannes; Thomas, Nicky; Müllertz, Anette

    2012-01-01

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

  19. Transformation from Multilamellar to Unilamellar Vesicles by Addition of a Cationic Lipid to PEGylated Liposomes Explored with Synchrotron Small Angle X-ray Scattering

    International Nuclear Information System (INIS)

    Sakuragi, Mina; Sakurai, Kazuo; Koiwai, Kazunori; Nakamura, Kouji; Masunaga, Hiroyasu; Ogawa, Hiroki

    2011-01-01

    PEGylated liposomes composed of a benzamidine derivative (TRX), hydrogenated soybean phosphatidylcholine (HSPC), and N-(monomethoxy-polyethyleneglycolcarbamyl) distearoyl phosphatidylethanolamine (PEG-PE) were examined in terms of how the addition of TRX affects their structures with small angle x-ray scattering (SAXS) as well as transmission electron microscopy (TEM). TEM images showed the presence of unilamella vesicles for both with and without TRX, though a small amount of multilamella vesicles were observed in absence of TRX. We analyzed SAXS profiles at contained TRX composition combined with contrast variation technique by adding PEG solution and unilamella vesicle model could be reproduced. Subsequently, we analyzed SAXS profiles at no TRX composition. The mixture model of unilamella and multilamella vesicle was reconstructed and we estimated about 10 % multilamella vesicles from a fitting parameter.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  1. 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.

  2. 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

  3. Interactions of a Photochromic Spiropyran with Liposome Model Membranes

    KAUST Repository

    Jonsson, Fabian

    2013-02-19

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

  4. Liposomal packaging generates Wnt protein with in vivo biological activity.

    Directory of Open Access Journals (Sweden)

    Nathan T Morrell

    2008-08-01

    Full Text Available Wnt signals exercise strong cell-biological and regenerative effects of considerable therapeutic value. There are, however, no specific Wnt agonists and no method for in vivo delivery of purified Wnt proteins. Wnts contain lipid adducts that are required for activity and we exploited this lipophilicity by packaging purified Wnt3a protein into lipid vesicles. Rather than being encapsulated, Wnts are tethered to the liposomal surface, where they enhance and sustain Wnt signaling in vitro. Molecules that effectively antagonize soluble Wnt3a protein but are ineffective against the Wnt3a signal presented by a cell in a paracrine or autocrine manner are also unable to block liposomal Wnt3a activity, suggesting that liposomal packaging mimics the biological state of active Wnts. When delivered subcutaneously, Wnt3a liposomes induce hair follicle neogenesis, demonstrating their robust biological activity in a regenerative context.

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

    Science.gov (United States)

    Cattel, Luigi; Ceruti, Maurizio; Dosio, Franco

    2003-01-01

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

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

    Science.gov (United States)

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

    2006-01-01

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

  7. 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.

  8. Tumor targeting using liposomal antineoplastic drugs

    Directory of Open Access Journals (Sweden)

    Jörg Huwyler

    2008-03-01

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

  9. 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

  10. Synchrotron X-ray scattering study on stratum corneum of skin. Toward applied research based upon basic research

    International Nuclear Information System (INIS)

    Hatta, Ichiro; Ohta, Noboru; Yagi, Naoto

    2008-01-01

    On considering the applied research on stratum corneum of skin, it is indispensable to know the structure at the molecular level. However, there is even now in a controversy among the researchers who are performing its X-ray scattering study. Here we introduce our solution for the two problems: One is the correlation between the lamellar structures and hydrocarbon-chain packings in intercellular lipid matrix and the other is the existence of water layers in the short lamellar structure. These studies have become possible for the first time by making good use of synchrotron small-angle/wide-angle X-ray diffraction. Based upon the structural evidence, we can further carry out the applied research in stratum corneum. (author)

  11. 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)

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

    Science.gov (United States)

    Mady, Mohsen M.; Elshemey, Wael M.

    2011-06-01

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

  13. 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.

  14. Hand eczema and stratum corneum ceramides

    DEFF Research Database (Denmark)

    Jungersted, J. M.; Høgh, Julie Kaae; Hellgren, Lars

    2015-01-01

    Index (HECSI), and skin barrier susceptibility was assessed by measuring transepidermal water loss (TEWL) after a 24-hour patch test with sodium lauryl sulfate (SLS). Results: No statistically significant difference was found between groups for the lipid analysis or for skin susceptibility to SLS. We...

  15. Liposome-encapsulated chemotherapy

    DEFF Research Database (Denmark)

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

    2018-01-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  17. Liposomes to target peripheral neurons and Schwann cells.

    Directory of Open Access Journals (Sweden)

    Sooyeon Lee

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

  18. Preparation and Use of Liposomes in Immunological Studies

    Science.gov (United States)

    1993-01-01

    using any serum, whether antiserum or complement. the serum must be extensively dialyzed to remove endogenous glucose. For complement we routinely...release method when compared to other liposome lysis assays is the presence of high levels of endogenous glucose in all sera, and frequently even in...Native lipid A from S. minnesota R595 (List) and monophospho- rosryl lipid A (Ribi) were 214-fold and 25-fold less pyrogenic than free lipid Volume 111 337

  19. 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...

  20. Biophysical aspects of using liposomes as delivery vehicles.

    Science.gov (United States)

    Ulrich, Anne S

    2002-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Jain PP

    2014-07-01

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

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

    Science.gov (United States)

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

    2002-01-01

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

  3. 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...

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

    Science.gov (United States)

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

    2006-01-01

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

  5. 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.

  6. Influence of DMPS on the water retention capacity of electroporated stratum corneum: ATR-FTIR study.

    Science.gov (United States)

    Sckolnick, Maria; Hui, Sek-Wen; Sen, Arindam

    2008-02-28

    Anionic lipids like phosphatidylserine are known to significantly enhance electroporation mediated transepidermal transport of polar solutes of molecular weights up to 10kDa. The underlying mechanism of the effect of anionic lipids on transdermal transport is not fully understood. The main barrier to transdermal transport lies within the intercellular lipid matrix (ILM) of the stratum corneum (SC) and our previous studies indicate that dimyristoyl phosphatidylserine (DMPS) can perturb the packing of this lipid matrix. Here we report on our investigation on water retention in the SC following electroporation in the presence and the absence of DMPS. The water content in the outer most layers of the SC of full thickness porcine skin was determined using ATR-FTIR-spectroscopy. The results show that in the presence of DMPS, the SC remains in a state of enhanced hydration for longer periods after electroporation. This increase in water retention in the SC by DMPS is likely to play an important role in trans-epidermal transport, since improved hydration of the skin barrier can be expected to increase the partitioning of polar solutes and possibly the permeability.

  7. Liposomal encapsulated Zn-DTPA for removing intracellular 169Yb

    International Nuclear Information System (INIS)

    Blank, M.L.; Cress, E.A.; Byrd, B.L.; Washburn, L.C.; Snyder, F.

    1980-01-01

    Multilamellar liposomes possessing neutral positive or negative charges were tested for their capacity to encapsulate sodium ethylenediaminetetraacetate (EDTA) and for their selectivity in depositing in specific tissues after being injected into rats. Negative-charged liposomes had the greatest trapping efficiency over a wide range of lipid-to-aqueous phase ratios. In contrast, except for lung, liposomal charge had no significant effect on the tissue distribution of encapsulated EDTA; liver and spleen exhibited the highest uptake with all preparations. The proportion of encapsulated EDTA taken up by the liver decreased as the amount of injected liposomes was increased. Free zinc diethylenetriaminepentaacetate (Zn-DTPA) and multilamellar liposomes containing entrapped Zn-DTPA were administered to rats that had been injected with 169 Yb-citrate 24 hr earlier. At doses of 14 mg Zn-DTPA per kg body weight, both free Zn-DPTA and the liposomal-bound Zn-DTPA caused increased removal of 169 Yb from the animals. However, treatment with the liposomal Zn-DTPA caused significantly more of the 169 Yb to be removed than did the free Zn-DTPA treatment by itself. Our data indicate that lipophilic forms of chelators can effectively increase the removal rates of heavy metal contamination in tissues. (author)

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

    International Nuclear Information System (INIS)

    Lipinski, Michael J.; Albelda, M. Teresa; Frias, Juan C.; Anderson, Stasia A.; Luger, Dror; Westman, Peter C.; Escarcega, Ricardo O.; Hellinga, David G.; Waksman, Ron; Arai, Andrew E.; Epstein, Stephen E.

    2016-01-01

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

  9. 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.

  10. Structural characterization and lipid composition of acquired cholesteatoma

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Svane-Knudsen, Viggo; Sørensen, Jens A

    2012-01-01

    HYPOTHESIS: The goal of this work is to characterize the morphology and lipid composition of acquired cholesteatoma. We hypothesize that constitutive lipid membranes are present in the cholesteatoma and resemble those found in human skin stratum corneum. METHODS: We performed a comparative...... noninvasive structural and lipid compositional study of acquired cholesteatoma and control human skin using multiphoton excitation fluorescence microscopy-related techniques and high-performance thin-layer chromatography. RESULTS: The structural arrangement of the cholesteatoma is morphologically invariant...... along a depth of more than 200 μm and resembles the stratum corneum of hyperorthokeratotic skin. Lipid compositional analyses of the cholesteatoma show the presence of all major lipid classes found in normal skin stratum corneum (ceramides, long chain fatty acids, and cholesterol). Consistent with this...

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

    Science.gov (United States)

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

    2017-10-01

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

  12. 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.

  13. 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.

  14. Stimuli-responsive Smart Liposomes in Cancer Targeting.

    Science.gov (United States)

    Jain, Ankit; Jain, Sanjay K

    2018-02-08

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

  15. Liposome Disruption Assay to Examine Lytic Properties of Biomolecules.

    Science.gov (United States)

    Jimah, John R; Schlesinger, Paul H; Tolia, Niraj H

    2017-08-05

    Proteins may have three dimensional structural or amino acid features that suggest a role in targeting and disrupting lipids within cell membranes. It is often necessary to experimentally investigate if these proteins and biomolecules are able to disrupt membranes in order to conclusively characterize the function of these biomolecules. Here, we describe an in vitro assay to evaluate the membrane lytic properties of proteins and biomolecules. Large unilamellar vesicles (liposomes) containing carboxyfluorescein at fluorescence-quenching concentrations are treated with the biomolecule of interest. A resulting increase in fluorescence due to leakage of the dye from liposomes and subsequent dilution in the buffer demonstrates that the biomolecule is sufficient for disrupting liposomes and membranes. Additionally, since liposome disruption may occur via pore-formation or via general solubilization of lipids similar to detergents, we provide a method to distinguish between these two mechanisms. Pore-formation can be identified and evaluated by examining the blockade of carboxyfluorescein release with dextran molecules that fit the pore. The methods described here were used to determine that the malaria vaccine candidate CelTOS and proapoptotic Bax disrupt liposomes by pore formation (Saito et al. , 2000; Jimah et al. , 2016). Since membrane lipid binding by a biomolecule precedes membrane disruption, we recommend the companion protocol: Jimah et al. , 2017.

  16. Deciphering the Functional Composition of Fusogenic Liposomes

    Science.gov (United States)

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

    2018-01-01

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

  17. ENERGY-TRANSDUCING PROPERTIES OF PRIMARY PROTON PUMPS RECONSTITUTED INTO ARCHAEAL BIPOLAR LIPID VESICLES

    NARCIS (Netherlands)

    ELFERINK, MGL; DEWIT, JG; DRIESSEN, AJM; KONINGS, WN; Elferink, Marieke G.L.

    1993-01-01

    Archaeal lipids differ considerably from eubacterial and eukaryotic lipids in their structure and physical properties. From the membranes of the extreme thermophilic archaea Sulfolobus acidocaldarius a tetraether lipid fraction was isolated, which can form closed and stable monolayer liposomes in

  18. Topical Application of Liposomal Antioxidants for Protection Against CEES Induced Skin Damage

    Science.gov (United States)

    2008-06-01

    within the liposome samples using HPLC with electro-chemical detection. As we mentioned above, the liposome membrane is fairly stable physically, even...lipid peroxidation Vitamin E or flavonoids , while not influencing hepatic GSH depletion, did reduce MDA levels, suggesting a therapeutic potential.19 The... flavonoid .32 Inhalation exposure to HD depleted hepatic GSH levels, and increased hepatic and lung lipid peroxidation (as indirectly measured by MDA

  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. 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.

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

    DEFF Research Database (Denmark)

    Jensen, Andreas Tue Ingemann

    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......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......‐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...

  2. Spin-labelling study of interactions of ovalbumin with multilamellar liposomes and specific anti-ovalbumin antibodies.

    Science.gov (United States)

    Brgles, Marija; Mirosavljević, Krunoslav; Noethig-Laslo, Vesna; Frkanec, Ruza; Tomasić, Jelka

    2007-03-10

    Ovalbumin (OVA) has been used continuously as the model antigen in numerous studies of immune reactions and antigen processing, very often encapsulated into liposomes. The purpose of this work was to study the possible interactions of spin-labelled OVA and lipids in liposomal membranes using electron spin resonance (ESR) spectroscopy. OVA was covalently spin-labelled with 4-maleimido-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO-maleimide), characterized and encapsulated into multilamellar, negatively charged liposomes. ESR spectra of this liposomal preparation gave evidence for the interaction of OVA with the lipid bilayers. Such an interaction was also evidenced by the ESR spectra of liposomal preparation containing OVA, where liposomes were spin-labelled with n-doxyl stearic acids. The spin-labelled OVA retains its property to bind specific anti-OVA antibodies, as shown by ESR spectroscopy, but also in ELISA for specific anti-OVA IgG.

  3. Interactions of a Photochromic Spiropyran with Liposome Model Membranes

    KAUST Repository

    Jonsson, Fabian; Beke-Somfai, Tamá s; André asson, Joakim; Nordé n, Bengt

    2013-01-01

    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

  4. 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...

  5. 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

  6. Improvement in physicochemical parameters of DPPC liposomes and increase in skin permeation of aciclovir and minoxidil by the addition of cationic polymers.

    Science.gov (United States)

    Hasanovic, Amra; Hollick, Caroline; Fischinger, Kerstin; Valenta, Claudia

    2010-06-01

    1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes were prepared by high-pressure homogeniser and coated with two cationic polymers, chitosan (CS) and for the first time Eudragit EPO (EU), respectively. Compared to the control liposomes, the polymeric liposomes showed greater physicochemical stability in terms of mean particle size and zeta potential at room temperature. In the present study, aciclovir and minoxidil have been used as hydrophilic and hydrophobic candidates. In the presence of the drugs, the polymeric liposomes still showed constant particle size and zeta potential. Influences of polymers and model drugs on thermotropic phase transition of DPPC liposomes were studied by micro-differential scanning calorimetry (microDSC). The influences on configuration of DPPC liposomes were investigated by Fourier transform infrared spectroscopy (FTIR). According to DSC results, cationic polymers had a stabilising effect, whereas aciclovir and minoxidil changed the physical properties of the DPPC bilayers by influencing the main phase transition temperature and erasing the pre-transition. The investigation of CO stretching bands of DPPC at 1736 cm(-1) in FTIR spectra showed that aciclovir has strong hydrogen bonding with CO groups of DPPC, whereas carbonyl groups were free in minoxidil presence. Moreover, the coating of liposomes with CS or EU led to higher skin diffusion for both drugs. This could be explained as an effect of positively charged liposomes to interact stronger with skin negatively charged surface and their possible interactions with structures below the stratum corneum. Copyright 2010 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  8. Enhanced bactericidal potency of nanoliposomes by modification of the fusion activity between liposomes and bacterium

    Directory of Open Access Journals (Sweden)

    Ma YF

    2013-06-01

    Full Text Available Yufan Ma,1 Zhao Wang,1,2 Wen Zhao,1 Tingli Lu,1 Rutao Wang,1,2 Qibing Mei,1 Tao Chen1–3 1Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, People's Republic of China; 2Shaanxi Liposome Research Center, Xi'an, Shaanxi, People's Republic of China; 3Xi'an Libang Pharmaceuticals Co, Ltd, Xi'an, People's Republic of China Background: Pseudomonas aeruginosa represents a good model of antibiotic resistance. These organisms have an outer membrane with a low level of permeability to drugs that is often combined with multidrug efflux pumps, enzymatic inactivation of the drug, or alteration of its molecular target. The acute and growing problem of antibiotic resistance of Pseudomonas to conventional antibiotics made it imperative to develop new liposome formulations to overcome these mechanisms, and investigate the fusion between liposome and bacterium. Methods: The rigidity, stability and charge properties of phospholipid vesicles were modified by varying the cholesterol, 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE, and negatively charged lipids 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol sodium salt (DMPG, 1,2-dimyristoyl-sn-glycero-3-phopho-L-serine sodium salt (DMPS, 1,2-dimyristoyl-sn-glycero-3-phosphate monosodium salt (DMPA, nature phosphatidylserine sodium salt from brain and nature phosphatidylinositol sodium salt from soybean concentrations in liposomes. Liposomal fusion with intact bacteria was monitored using a lipid-mixing assay. Results: It was discovered that the fluid liposomes-bacterium fusion is not dependent on liposomal size and lamellarity. A similar degree of fusion was observed for liposomes with a particle size from 100 to 800 nm. The fluidity of liposomes is an essential pre-request for liposomes fusion with bacteria. Fusion was almost completely inhibited by incorporation of cholesterol into fluid liposomes. The increase in the

  9. Radiation-induced changes of liposomes and lecithin in non-aqueous media

    International Nuclear Information System (INIS)

    Nakazawa, T.; Nagatsuka, S.; Sakurai, T.

    1981-01-01

    Radiation-induced changes of lipids in non-aqueous media were studied to elucidate the process of radiation damage in biological membranes. The lipid peroxidation progressed linearly with increasing dose and decreasing dose rate of γ-irradiation in soyabean lecithin in chloroform. The fatty acid composition of lecithin also changed, especially in linoleic and linolenic acids. Lower dose rate radiation enhanced these changes in oxic condition. Lipid peroxidation was also shown in lipids extracted from irradiated liposomes or in liposomes prepared from irradiated lecithin in chloroform. The dose-dependent glucose efflux was seen in liposomes prepared from irradiated lecithin in chloroform. These results indicate that the peroxidation of lipid molecules might cause radiation damage to the membrane conformation. (author)

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

    Science.gov (United States)

    Smith, Cartney E; Kong, Hyunjoon

    2014-04-08

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

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

    International Nuclear Information System (INIS)

    Tugulea, Laura; Miclaus, Simona; Iacovache, Ioan

    2001-01-01

    The liposomes with Chlorophyll are excellent model membranes and could be successfully used to study the electromagnetic influence at molecular level. The strong visible absorption and fluorescence of Chlorophyll allow its use as sensor for the interactions at molecular level and as a fluorescence marker; it reflects certain aspects of the supramolecular structure of the lipid phase: fluidity, lipid and liposomes aggregation. The objective of our work was to evidence athermal effect of low level, pulsed microwave (MW) fields on liposomes and to evidence the possible mechanism of interaction at molecular level. Unilamellar liposomes were obtained from multilamellar vesicles by the hand-shaken method and sonication for 30 minutes. The multilamellar vesicles were prepared using Chla /lipid films with specific molar ratio (lipid/Chla 1/10 and 1/100) and different lipids (Dipalmitoyl phosphatidylcholine, Dimirystoyl Phosphatidylcholine and Dioleoyl Phosphatidylcholine-Sigma). The films were dispersed in buffer solutions of different pH (6.2 - 7.6). The Chlorophyll was freshly extracted from spinach leaves and separated by the chromatographic method. Portions of liposome suspension (0.6 ml) were inserted into Teflon cuvettes. The samples were irradiated in series, for periods of 5-30 minutes. The exposure system was: MW generator + adapted load (shortened rectangular waveguide) + Teflon cuvette filled with sample liquid. The effect of MW irradiation is not observable on multilamellar vesicles, but only on small unilamellar vesicles. The MW effect is athermal, verified by conventional heating in the same range of temperatures and results in enlarging the size of vesicles. The enlarging effect of MW is opposed to the effect of ultrasounds exposure. It is not clear if effects due to MW are proportional with exposure duration; it seems that this mostly depends on the type of lipid in vesicles. The UV and VIS spectra were recorded to observe the oxidation state of the

  12. Mechanistic Studies on the Triggered Release of Liposomal Contents by Matrix Metalloproteinase-9

    Science.gov (United States)

    Elegbede, Adekunle I.; Banerjee, Jayati; Hanson, Andrea J.; Tobwala, Shakila; Ganguli, Bratati; Wang, Rongying; Lu, Xiaoning; Srivastava, D. K.; Mallik, Sanku

    2009-01-01

    Matrix metalloproteinases (MMPs) are a class of extracellular matrix degrading enzymes over-expressed in many cancers and contribute to the metastatic ability of the cancer cells. We have recently demonstrated that liposomal contents can be released when triggered by the enzyme MMP-9. Herein, we report our results on the mechanistic studies of the MMP-9 triggered release of the liposomal contents. We synthesized peptides containing the cleavage site for MMP-9 and conjugated them with fatty acids to prepare the corresponding lipopeptides. By employing Circular Dichroism spectroscopy, we demonstrate that the lipopeptides, when incorporated in liposomes, are de-mixed in the lipid bilayers and generate triple helical structures. MMP-9 cleaves the triple helical peptides, leading to the release of the liposomal contents. Other MMPs, which cannot hydrolyze triple helical peptides, failed to release the contents from the liposomes. We also observed that the rate and the extent of release of the liposomal contents depend on the mismatch between acyl chains of the synthesized lipopeptide and phospholipid components of the liposomes. Circular Dichroism spectroscopic studies imply that the observed differences in the release reflect the ability of the liposomal membrane to anneal the defects following the enzymatic cleavage of the liposome-incorporated lipopeptides. PMID:18642903

  13. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-06-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Giorgia Giacometti

    2017-11-01

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

  17. Two dimensional finite element modelling for dynamic water diffusion through stratum corneum.

    Science.gov (United States)

    Xiao, Perry; Imhof, Robert E

    2012-10-01

    Solvents penetration through in vivo human stratum corneum (SC) has always been an interesting research area for trans-dermal drug delivery studies, and the importance of intercellular routes (diffuse in between corneocytes) and transcellular routes (diffuse through corneocytes) during diffusion is often debatable. In this paper, we have developed a two dimensional finite element model to simulate the dynamic water diffusion through the SC. It is based on the brick-and-mortar model, with brick represents corneocytes and mortar represents lipids, respectively. It simulates the dynamic water diffusion process through the SC from pre-defined initial conditions and boundary conditions. Although the simulation is based on water diffusions, the principles can also be applied to the diffusions of other topical applied substances. The simulation results show that both intercellular routes and transcellular routes are important for water diffusion. Although intercellular routes have higher flux rates, most of the water still diffuse through transcellular routes because of the high cross area ratio of corneocytes and lipids. The diffusion water flux, or trans-epidermal water loss (TEWL), is reversely proportional to corneocyte size, i.e. the larger the corneocyte size, the lower the TEWL, and vice versa. There is also an effect of the SC thickness, external air conditions and diffusion coefficients on the water diffusion through SC on the resulting TEWL. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. 6-mercaptopurine and daunorubicin double drug liposomes-preparation, drug-drug interaction and characterization.

    Science.gov (United States)

    Agrawal, Vineet; Paul, Manash K; Mukhopadhyay, Anup K

    2005-01-01

    This article addresses and investigates the dual incorporation of daunorubicin (DR) and 6-mercaptopurine (6-MP) in liposomes for better chemotherapy. These drugs are potential candidates for interaction due to the quinone (H acceptor) and hydroxyl (H donor) groups on DR and 6-MP, respectively. Interactions between the two drugs in solution were monitored by UV/Vis and fluorescence spectroscopy. Interaction between the two drugs inside the liposomes was evaluated by HPLC (for 6-MP) and by fluorescence spectroscopy (for daunorubicin) after phospholipase-mediated liposome lysis. Our results provide evidence for the lack of interaction between the two drugs in solution and in liposomes. The entrapment efficiencies of 6-MP in the neutral Phosphatidyl choline (PC):Cholesterol (Chol):: 2:1 and anionic PC:Chol:Cardiolipin (CL) :: 4:5:1 single and double drug liposomes were found to be 0.4% and 1.5% (on average), respectively. The entrapment efficiencies of DR in the neutral and anionic double drug liposomes were found to be 55% and 31%, respectively. The corresponding entrapment of daunorubicin in the single drug liposomes was found to be 62% on average. Our thin layer chromatography (TLC) and transmission electron microscopy (TEM) results suggest stability of lipid and liposomes, thus pointing plausible existence of double drug liposomes. Cytotoxicity experiments were performed by using both single drug and double drug liposomes. By comparing the results of phase contrast and fluorescence microscopy, it was observed that the double drug liposomes were internalized in the jurkat and Hut78 (highly resistant cell line) leukemia cells as viewed by the fluorescence of daunorubicin. The cytotoxicity was dose dependent and had shown a synergistic effect when double drug liposome was used.

  19. trimethylammoniumpropane-based Liposomes

    African Journals Online (AJOL)

    mechanisms to introduce therapeutic agents into the body. Currently, the ... Liposomes are biodegradable and non-toxic and can elicit both ... buffered saline by dissolving a vial in 40 ml phosphate ... vaccines were processed using copper grids to adsorb the .... time-dependent fluctuations in the intensity of scattered light ...

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

    Science.gov (United States)

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

    2013-07-01

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

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

    Science.gov (United States)

    Zizzari, Alessandra; Bianco, Monica; Perrone, Elisabetta; Amato, Francesco; Maruccio, Giuseppe; Rendina, Filippo; Arima, Valentina

    2017-01-01

    Injectable liposomes are characterized by a suitable size and unique lipid mixtures, which require time-consuming and nonstraightforward production processes. The complexity of the manufacturing methods may affect liposome solubility, the phase transition temperatures of the membranes, the average particle size, and the associated particle size distribution, with a possible impact on the drug encapsulation and release. By leveraging the precise steady-state control over the mixing of miscible liquids and a highly efficient heat transfer, microfluidic technology has proved to be an effective and direct methodology to produce liposomes. This approach results particularly efficient in reducing the number of the sizing steps, when compared to standard industrial methods. Here, Microfluidic Hydrodynamic Focusing chips were produced and used to form liposomes upon tuning experimental parameters such as lipids concentration and Flow-Rate-Ratios (FRRs). Although modelling evidenced the dependence of the laminar flow on the geometric constraints and the FRR conditions, for the specific formulation investigated in this study, the lipids concentration was identified as the primary factor influencing the size of the liposomes and their polydispersity index. This was attributed to a predominance of the bending elasticity modulus over the vesiculation index in the lipid mixture used. Eventually, liposomes of injectable size were produced using microfluidic one-pot synthesis in continuous flow. PMID:29232873

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Mohammad Kargar

    2016-06-01

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

  4. Partitioning of polychlorinated biphenyls into human cells and adipose tissues: evaluation of octanol, triolein, and liposomes as surrogates

    NARCIS (Netherlands)

    Quinn, Cristina L.; Van Der Heijden, Stephan A.; Wania, Frank; Jonker, Michiel T O

    2014-01-01

    Whereas octanol, triacylglycerides, and liposomes have all been proposed as surrogates for measuring the affinity of hydrophobic organic contaminants to human lipids, no comparative evaluation of their suitability exists. Here we conducted batch sorption experiments with polyoxymethylene passive

  5. Microspectroscopic Study of Liposome-to-cell Interaction Revealed by Förster Resonance Energy Transfer.

    Science.gov (United States)

    Yefimova, Svetlana L; Kurilchenko, Irina Yu; Tkacheva, Tatyana N; Kavok, Nataliya S; Todor, Igor N; Lukianova, Nataliya Yu; Chekhun, Vasyl F; Malyukin, Yuriy V

    2014-03-01

    We report the Förster resonance energy transfer (FRET)-labeling of liposomal vesicles as an effective approach to study in dynamics the interaction of liposomes with living cells of different types (rat hepatocytes, rat bone marrow, mouse fibroblast-like cells and human breast cancer cells) and cell organelles (hepatocyte nuclei). The in vitro experiments were performed using fluorescent microspectroscopic technique. Two fluorescent dyes (DiO as the energy donor and DiI as an acceptor) were preloaded in lipid bilayers of phosphatidylcholine liposomes that ensures the necessary distance between the dyes for effective FRET. The change in time of the donor and acceptor relative fluorescence intensities was used to visualize and trace the liposome-to-cell interaction. We show that FRET-labeling of liposome vesicles allows one to reveal the differences in efficiency and dynamics of these interactions, which are associated with composition, fluidity, and metabolic activity of cell plasma membranes.

  6. Protective Effect of Liposome-Encapsulated Glutathione in a Human Epidermal Model Exposed to a Mustard Gas Analog

    Directory of Open Access Journals (Sweden)

    Victor Paromov

    2011-01-01

    Full Text Available Sulfur mustard or mustard gas (HD and its monofunctional analog, 2-chloroethyl ethyl sulfide (CEES, or “half-mustard gas,” are alkylating agents that induce DNA damage, oxidative stress, and inflammation. HD/CEES are rapidly absorbed in the skin causing extensive injury. We hypothesize that antioxidant liposomes that deliver both water-soluble and lipid-soluble antioxidants protect skin cells from immediate CEES-induced damage via attenuating oxidative stress. Liposomes containing water-soluble antioxidants and/or lipid-soluble antioxidants were evaluated using in vitro model systems. Initially, we found that liposomes containing encapsulated glutathione (GSH-liposomes increased cell viability and attenuated production of reactive oxygen species (ROS in HaCaT cells exposed to CEES. Next, GSH-liposomes were tested in a human epidermal model, EpiDerm. In the EpiDerm, GSH-liposomes administered simultaneously or 1 hour after CEES exposure (2.5 mM increased cell viability, inhibited CEES-induced loss of ATP and attenuated changes in cellular morphology, but did not reduce caspase-3 activity. These findings paralleled the previously described in vivo protective effect of antioxidant liposomes in the rat lung and established the effectiveness of GSH-liposomes in a human epidermal model. This study provides a rationale for use of antioxidant liposomes against HD toxicity in the skin considering further verification in animal models exposed to HD.

  7. 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)

  8. Design and Synthesis of Archaea-Inspired Tetraether Lipids

    Science.gov (United States)

    Koyanagi, Takaoki

    Maintaining the correct ion homeostasis across membranes is a major challenge in both nature and artificial systems. Archaea, have evolved to solve membrane permeability problems to survive in extreme environments by incorporating unique structural features found in their lipid. Specifically, inclusion of phytanyl side chains, ether glycerol linkages, tethering of lipids, cycloalkanes, and different polar lipid headgroups into their lipid membrane are believed to contribute to membrane stability. We sought to gain a better understanding of the functional benefits attributed to these structural features to membrane stability to design a new class of synthetic Archaea inspired lipid membranes that can be used to overcome limitations (i.e. unstable in serum environment, high background leakage, and prone to hydrolysis) found in current lipid based technologies. Leakage experiments revealed liposomes made from GMGTPC (glycerol monoalkyl glycerol tetraether lipid with phosphatidylcholine headgroup) demonstrated a two order magnitude reduction in membrane leakage to small ions when compared with liposomes made from EggPC. Additionally, liposomes composed of GMGTPC-CH (cyclohexane integrated) lipid displayed an additional 40% decrease in membrane leakage to small ions when compared with liposomes made from GMGTPC lipids. Furthermore, leakage experiments revealed a higher degree of tolerance to headgroup modifications to membrane leakage for liposomes made from GMGT lipid analogs when compared with liposomes made from POPC. After designing an optimal tetraether lipid scaffold that incorporates key Archaeal structural features for membrane leakage, we explored to integrate strategies employed by eukaryotes to improve membrane properties (i.e. addition of cholesterol). Liposomes made from the hybrid lipid, GcGTPC-CH, displayed a five-fold decrease in membrane leakage when compared with liposomes made from GMGTPC-CH, while maintaining functional membrane properties similar to

  9. 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

  10. 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.

  11. Water distribution and related morphology in human stratum corneum at different hydration levels

    NARCIS (Netherlands)

    Bouwstra, J.A.; Graaff, de A.; Gooris, G.S.; Nijsse, J.; Wiechers, J.W.; Aelst, van A.C.

    2003-01-01

    This study focused on the water distribution in human stratum corneum and on the swelling of the corneocytes. For this purpose stratum corneum was hydrated to various levels and used either for Fourier transform infrared spectroscopy or for cryo-scanning electron microscopy. The images were analyzed

  12. Electroperturbation of human stratum corneum fine structure by high voltage pulses: a freeze-fracture electron microscopy and differential thermal analysis study.

    Science.gov (United States)

    Jadoul, A; Tanojo, H; Préat, V; Bouwstra, J A; Spies, F; Boddé, H E

    1998-08-01

    Application of high voltage pulses (HVP) to the skin has been shown to promote the transdermal drug delivery by a mechanism involving skin electroporation. The aim of this study was to detect potential changes in lipid phase and ultrastructure induced in human stratum corneum by various HVP protocols, using differential thermal analysis and freeze-fracture electron microscopy. Due to the time involved between the moment the electric field is switched off and the analysis, only "secondary" phenomena rather than primary events could be observed. A decrease in enthalpies for the phase transitions observed at 70 degrees C and 85 degrees C was detected by differential thermal analysis after HVP treatment. No changes in transition temperature could be seen. The freeze-fracture electron microscopy study revealed a dramatic perturbation of the lamellar ordering of the intercellular lipid after application of HVP. Most of the planes displayed rough surfaces. The lipid lamellae exhibited rounded off steps or a vanished stepwise order. There was no evidence for perturbation of the corneocytes content. In conclusion, the freeze-fracture electron microscopy and differential thermal analysis studies suggest that HVP application induces a general perturbation of the stratum corneum lipid ultrastructure.

  13. Benchmarking of Sterilizing grade filters with liposome Filtration.

    Science.gov (United States)

    Loewe, Thomas; Mundlamuri, Ramesh; Loewe, Thomas; Mundrigi, Ashok; Handt, Sebastian; Singh, Bhuwan

    2017-12-14

    Cytotoxic drugs can be encapsulated in liposomes vesicles, which act as drug delivery vehicles and reduce the risk of exposure of drug to healthy cells(1). The sterility of such liposome solutions is typically ensured using 0.2μm rated sterilizing grade membranes, but due to the high viscosity and low surface tension of these formulations, they can cause pre-mature blocking and increased risk of bacterial penetration through a 0.2μm sterilizing grade membrane(2). The low surface tension of liposome solutions affects the contact angle with membrane and reduces bubble point leading to bacterial penetration through the membrane. This poses a great challenge to select an appropriate sterilizing grade membrane for a given process and for filter manufacturers to develop a sterilizing grade membrane that specifically addresses these needs. In this study, the influence of different variables that could affect the total throughput and bacterial retention performance of different membranes types on processing of liposome solutions have been evaluated. Based on the results, we conclude that the membrane properties e.g., surface porosity, surface tension, pore size, symmetry/asymmetry, hydrophilicity and liposome properties e.g., composition, lipid size and concentration affect bacterial retention and total throughput capacity. Process parameters such as temperature, pressure and flow should also be optimized to improve process efficiency. Copyright © 2017, Parenteral Drug Association.

  14. 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.

  15. 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.

  16. Preparation of 99mTc-HYNIC-PEG-liposomes for imaging of the focal sites infection

    International Nuclear Information System (INIS)

    Hong, Jun Pyo; Awh, Ok Doo; Kim, Hyun Suk; Lee, Eun Sook; Lee, Tae Sup; Choi, Tae Hyun; Choi, Chang Woon; Lim, Sang Moo

    2002-01-01

    A new linker, hydrazino nicotinamide (HYNIC), was recently introduced for labelling of liposome with 99m Tc. In this study we synthesized HYNIC derivatized PEG (polyethylene glycol)-liposomes radiolabeled with 99m Tc. In order to synthesize HYNIC-DSPE (distearoyl phosphatidyl ethanolamine) which is a crucial component for 99m Tc chelation, first of all succinimidyl 6-BOC-hydrazinopyridine-3-carboxylic acid was synthesized from 6-chloronicotinic acid by three sequential reactions. A DSPE derivative of succinimidyl 6-BOC-hydrazinopyridine-3-carboxylic acid was transformed into HYNIC-DSPE by HCI/dioxane. HYNIC-PEG-liposomes were prepared by hydration of the dried lipid mixture of EPC (egg phosphatidyl choline): PEG-DSPE : HYNIC-DSPE: cholesterol (1.85:0.15:0.07:1, molar ratio). The HYNIC-PEG-liposomes were labeled with 99m Tc in the presence of SnCl 2 ·2H 2 O (a reducing agent) and tricine (a colignad). To investigate the level of in vivo transchelation of 99m Tc in the liposomes, the 99m Tc-HYNIC-PEG-liposomes were incubated with a molar excess of DTPA, cysteine or glutathione solutions at 37 .deg. C for 24 hours. 6-BOC-hydrazinopyridine-3-carboxylic acid was synthesized with 77.3% overall yield. The HYNIC concentration in the PEG-coated liposome dispersion was 1.08 mM. In condition of considering the measured liposome size of 106 nm, the phospholipid concentration of 77.5 μmol/ ml and the liposomal particle number of 5.2x10 14 liposomes/ml, it is corresponded to approximate 1,250 nicotinyl hydrazine group per liposome in HYNIC-PEG-liposome. The removal of free 99m Tc was not necessary because the labeling efficiency were above 99%. The radiolabeled liposomes maintained 98%, 96% and 99%, respectively, of radioactivity after incubation with transchelators. The radiolabeled liposomes possessed above 90% of the radioactivity in serum. These results suggest that the HYNIC can be synthesized easily and applied in labelling of PEG-liposomes with 99m Tc

  17. Mechanical properties of a Gelidium corneum edible film containing catechin and its application in sausages.

    Science.gov (United States)

    Ku, K-J; Hong, Y-H; Song, K B

    2008-04-01

    We prepared an edible Gelidium corneum (GC) film containing catechin and examined the microbial growth and quality change during storage of sausages packaged with the film. Incorporation of catechin in the film improved film tensile strength and water vapor permeability. The film's antimicrobial activity against Eschericha coli O157:H7 increased with increasing catechin concentrations and resulted in a decrease in the populations of the bacteria by 1.93 log CFU/g at 150 mg of catechin. For the sausage samples inoculated with E. coli O157:H7 and Listeria monocytogenes, the samples packed with the GC film showed a decrease in populations of E. coli O157:H7 and L. monocytogenes by 1.81 and 1.44 log CFU/g, respectively, compared to the control after 5 d of storage. In addition, the sausage samples packed with the GC film had lower degrees of lipid oxidation. The results suggest that sausages can be packed with GC film to extend shelf life.

  18. Non steady-state descriptions of drug permeation through stratum corneum. I. The biphasic brick-and-mortar model.

    Science.gov (United States)

    Heisig, M; Lieckfeldt, R; Wittum, G; Mazurkevich, G; Lee, G

    1996-03-01

    The diffusion equation should be solved for the non-steady-state problem of drug diffusion within a two-dimensional, biphasic stratum corneum membrane having homogeneous lipid and corneocyte phases. A numerical method was developed for a brick-and-mortar SC-geometry, enabling an explicit solution for time-dependent drug concentration within both phases. The lag time and permeability were calculated. It is shown how the barrier property of this model membrane depends on relative phase permeability, corneocyte alignment, and corneocyte-lipid partition coefficient. Additionally, the time-dependent drug concentration profiles within the membrane can be observed during the lag and steady-state phases. The model SC-membrane predicts, from purely morphological principles, lag times and permeabilities that are in good agreement with experimental values. The long lag times and very small permeabilities reported for human SC can only be predicted for a highly-staggered corneocyte geometry and corneocytes that are 1000 times less permeable than the lipid phase. Although the former conclusion is reasonable, the latter is questionable. The elongated, flattened corneocyte shape renders lag time and permeability insensitive to large changes in their alignment within the SC. Corneocyte/lipid partitioning is found to be fundamentally different to SC/donor partitioning, since increasing drug lipophilicity always reduces both lag time and permeability.

  19. Liposome-based Formulation for Intracellular Delivery of Functional Proteins

    Directory of Open Access Journals (Sweden)

    Benoît Chatin

    2015-01-01

    Full Text Available The intracellular delivery of biologically active protein represents an important emerging strategy for both fundamental and therapeutic applications. Here, we optimized in vitro delivery of two functional proteins, the β-galactosidase (β-gal enzyme and the anti-cytokeratin8 (K8 antibody, using liposome-based formulation. The guanidinium-cholesterol cationic lipid bis (guanidinium-tren-cholesterol (BGTC (bis (guanidinium-tren-cholesterol combined to the colipid dioleoyl phosphatidylethanolamine (DOPE (dioleoyl phosphatidylethanolamine was shown to efficiently deliver the β-gal intracellularly without compromising its activity. The lipid/protein molar ratio, protein amount, and culture medium were demonstrated to be key parameters affecting delivery efficiency. The protein itself is an essential factor requiring selection of the appropriate cationic lipid as illustrated by low K8 binding activity of the anti-K8 antibody using guanidinium-based liposome. Optimization of various lipids led to the identification of the aminoglycoside lipid dioleyl succinyl paromomycin (DOSP associated with the imidazole-based helper lipid MM27 as a potent delivery system for K8 antibody, achieving delivery in 67% of HeLa cells. Cryo-transmission electron microscopy showed that the structure of supramolecular assemblies BGTC:DOPE/β-gal and DOSP:MM27/K8 were different depending on liposome types and lipid/protein molar ratio. Finally, we observed that K8 treatment with DOSP:MM27/K8 rescues the cyclic adenosine monophosphate (cAMP-dependent chloride efflux in F508del-CFTR expressing cells, providing a new tool for the study of channelopathies.

  20. DNA release from lipoplexes by anionic lipids: correlation with lipid mesomorphism, interfacial curvature, and membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Tarahovsky, Yury S.; Koynova, Rumiana; MacDonald, Robert C. (Northwestern)

    2010-01-18

    DNA release from lipoplexes is an essential step during lipofection and is probably a result of charge neutralization by cellular anionic lipids. As a model system to test this possibility, fluorescence resonance energy transfer between DNA and lipid covalently labeled with Cy3 and BODIPY, respectively, was used to monitor the release of DNA from lipid surfaces induced by anionic liposomes. The separation of DNA from lipid measured this way was considerably slower and less complete than that estimated with noncovalently labeled DNA, and depends on the lipid composition of both lipoplexes and anionic liposomes. This result was confirmed by centrifugal separation of released DNA and lipid. X-ray diffraction revealed a clear correlation of the DNA release capacity of the anionic lipids with the interfacial curvature of the mesomorphic structures developed when the anionic and cationic liposomes were mixed. DNA release also correlated with the rate of fusion of anionic liposomes with lipoplexes. It is concluded that the tendency to fuse and the phase preference of the mixed lipid membranes are key factors for the rate and extent of DNA release. The approach presented emphasizes the importance of the lipid composition of both lipoplexes and target membranes and suggests optimal transfection may be obtained by tailoring lipoplex composition to the lipid composition of target cells.

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

    Science.gov (United States)

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

    2014-01-14

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

  2. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-04-15

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

  4. 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.

  5. Efficient intradermal delivery of superoxide dismutase using a combination of liposomes and iontophoresis for protection against UV-induced skin damage.

    Science.gov (United States)

    Kigasawa, Kaoru; Miyashita, Moeko; Kajimoto, Kazuaki; Kanamura, Kiyoshi; Harashima, Hideyoshi; Kogure, Kentaro

    2012-01-01

    Superoxide dismutase (SOD) is a potent antioxidant agent that protects against UV-induced skin damage. However, its high molecular weight is a significant obstacle for efficient delivery into the skin through the stratum corneum and development of antioxidant activity. Recently, we developed a non-invasive transfollicular delivery system for macromolecules using a combination of liposomes and iontophoresis, that represents promising technology for enhancing transdermal administration of charged drugs (IJP, 403, 2011, Kajimoto et al.). In this study, in rats we attempted to apply this system to intradermal delivery of SOD for preventing UV-induced skin injury. SOD encapsulating in cationic liposomes was subjected to anodal iontophoresis. After iontophoretic treatment, the liposomes were diffused widely in the viable skin layer around hair follicles. In contrast, passive diffusion failed to transport liposomes efficiently into the skin. Iontophoretic delivery of liposomes encapsulating SOD caused a marked decrease in the production of oxidative products, such as malondialdehyde, hexanoyl lysine, and 8-hydroxi-2-deoxyguanosine, in UV-irradiated skin. These findings suggested that functional SOD can be delivered into the skin using a combination of iontophoresis and a liposomal system. In conclusion, we succeeded in developing an efficient intradermal SOD delivery system, that would be useful for delivery of other macromolecules.

  6. Optimization of drug loading to improve physical stability of paclitaxel-loaded long-circulating liposomes.

    Science.gov (United States)

    Kannan, Vinayagam; Balabathula, Pavan; Divi, Murali K; Thoma, Laura A; Wood, George C

    2015-01-01

    The effect of formulation and process parameters on drug loading and physical stability of paclitaxel-loaded long-circulating liposomes was evaluated. The liposomes were prepared by hydration-extrusion method. The formulation parameters such as total lipid content, cholesterol content, saturated-unsaturated lipid ratio, drug-lipid ratio and process parameters such as extrusion pressure and number of extrusion cycles were studied and their impact on drug loading and physical stability was evaluated. A proportionate increase in drug loading was observed with increase in the total phospholipid content. Cholesterol content and saturated lipid content in the bilayer showed a negative influence on drug loading. The short-term stability evaluation of liposomes prepared with different drug-lipid ratios demonstrated that 1:60 as the optimum drug-lipid ratio to achieve a loading of 1-1.3 mg/mL without the risk of physical instability. The vesicle size decreased with an increase in the extrusion pressure and number of extrusion cycles, but no significant trends were observed for drug loading with changes in process pressure or number of cycles. The optimization of formulation and process parameters led to a physically stable formulation of paclitaxel-loaded long-circulating liposomes that maintain size, charge and integrity during storage.

  7. Mucosal delivery of liposome-chitosan nanoparticle complexes.

    Science.gov (United States)

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

    2009-01-01

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

  8. 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.

  9. 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)

  10. Exchangeable pulmonary water space evaluation using giant liposomes

    International Nuclear Information System (INIS)

    Santos, A.C.; Ribeiro, M.J.; Ferreira, N.; De Lima, J.J.P.

    1998-01-01

    The present work aims to study the potential use of liposomes for the evaluation of pulmonary exchangeable water space, important parameter in some pulmonary oedema situations. This study is based upon the delivery of a diffusible water radiotracer into pulmonary capillary network, which equilibrates with interstitial water space of the lung and returns to the blood circulation. The time constant of this phenomena depends on the magnitude of the water space under study. The release of the diffusible radiotracer in lung capillaries is performed using liposomes with specific formulation. The giant liposomes (15-30μm diameter) used in this study are instable at 37 deg. C. They are biocompatible, biodegradable, with low toxicity and showed no immunogenicity. A water tracer labelled with 99m Tc, encapsulated in the aqueous phase of giant liposomes, has been used. Liposomes were prepared in sterile conditions and with apyrogenic materials. The lipid films composition is L-α-diestearoylphosphatidylcholine (DSPC), L-α-phosphatidyl-DL-glycerol (EPG) and cholesterol (CHOL) (60%/10%/30% mass ratio). After iv injection at +-20 deg. C in the femoral vein of Wistar rats (300g-600g) or albine rabbits (4.5-5Kg), the thermolabile liposomes will be entrapped in lung capillaries and release the radiotracer locally. When the radiodrug is diffusible we will evaluate the volume of the exchangeable pulmonary water analyzing the activity/time curves. These curves are slower for greater water spaces. When the radiotracer is non-diffusible, the disappearance curves are not influenced by the extravascular water space. (author)

  11. Membrane Microdomain Structures of Liposomes and Their Contribution to the Cellular Uptake Efficiency into HeLa Cells.

    Science.gov (United States)

    Onuki, Yoshinori; Obata, Yasuko; Kawano, Kumi; Sano, Hiromu; Matsumoto, Reina; Hayashi, Yoshihiro; Takayama, Kozo

    2016-02-01

    The purpose of this study is to obtain a comprehensive relationship between membrane microdomain structures of liposomes and their cellular uptake efficiency. Model liposomes consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/cholesterol (Ch) were prepared with various lipid compositions. To detect distinct membrane microdomains in the liposomes, fluorescence-quenching assays were performed at temperatures ranging from 25 to 60 °C using 1,6-diphenyl-1,3,5-hexatriene-labeled liposomes and (2,2,6,6-tetramethylpiperidin-1-yl)oxyl. From the data analysis using the response surface method, we gained a better understanding of the conditions for forming distinct domains (Lo, Ld, and gel phase membranes) as a function of lipid composition. We further performed self-organizing maps (SOM) clustering to simplify the complicated behavior of the domain formation to obtain its essence. As a result, DPPC/DOPC/Ch liposomes in any lipid composition were integrated into five distinct clusters in terms of similarity of the domain structure. In addition, the findings from synchrotron small-angle X-ray scattering analysis offered further insight into the domain structures. As a last phase of this study, an in vitro cellular uptake study using HeLa cells was conducted using SOM clusters' liposomes with/without PEGylation. As a consequence of this study, higher cellular uptake was observed from liposomes having Ch-rich ordered domains.

  12. The effect of the chain length distribution of free fatty acids on the mixing properties of stratum corneum model membranes.

    Science.gov (United States)

    Oguri, Masashi; Gooris, Gert S; Bito, Kotatsu; Bouwstra, Joke A

    2014-07-01

    The stratum corneum (SC) plays a fundamental role in the barrier function of the skin. The SC consists of corneocytes embedded in a lipid matrix. The main lipid classes in the lipid matrix are ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs). The aim of this study was to examine the effect of the chain length of FFAs on the thermotropic phase behavior and mixing properties of SC lipids. Fourier transform infrared spectroscopy and Raman imaging spectroscopy were used to study the mixing properties using either protonated or deuterated FFAs. We selected SC model lipid mixtures containing only a single CER, CHOL and either a single FFA or a mixture of FFAs mimicking the FFA SC composition. The single CER consists of a sphingoid base with 18 carbon atoms and an acyl chain with a chain length of 24 carbon atoms. When using lignoceric acid (24 carbon atoms) or a mixture of FFAs, the CER and FFAs participated in mixed crystals, but hydration of the mixtures induced a slight phase separation between CER and FFA. The mixed crystalline structures did not phase separate during storage even up to a time period of 3months. When using palmitic acid (16 carbon atoms), a slight phase separation was observed between FFA and CER. This phase separation was clearly enhanced during hydration and storage. In conclusion, the thermotropic phase behavior and the mixing properties of the SC lipid mixtures were shown to strongly depend on the chain length and chain length distribution of FFAs, while hydration enhanced the phase separation. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Water insoluble and soluble lipids for gene delivery.

    Science.gov (United States)

    Mahato, Ram I

    2005-04-05

    Among various synthetic gene carriers currently in use, liposomes composed of cationic lipids and co-lipids remain the most efficient transfection reagents. Physicochemical properties of lipid/plasmid complexes, such as cationic lipid structure, cationic lipid to co-lipid ratio, charge ratio, particle size and zeta potential have significant influence on gene expression and biodistribution. However, most cationic lipids are toxic and cationic liposomes/plasmid complexes do not disperse well inside the target tissues because of their large particle size. To overcome the problems associated with cationic lipids, we designed water soluble lipopolymers for gene delivery to various cells and tissues. This review provides a critical discussion on how the components of water insoluble and soluble lipids affect their transfection efficiency and biodistribution of lipid/plasmid complexes.

  14. Radiation-induced changes in membrane hydrophobicity in liposomes

    International Nuclear Information System (INIS)

    Nakazawa, Tohru; Nagatsuka, Shinichiro; Yukawa, Osami

    1985-01-01

    Effects of γ-radiation on the physical state of membranes were examined with liposomes of lecithin (phosphatidylcholine) from soybean and rat liver microsomes using spin labeling method. There was a slight increase in the membrane fluidity after irradiation. However, a marked decrease in the membrane hydrophobicity by irradiation was observed in the peripheral region in both types of membranes, in parallel with an increase in the lipid peroxidation. These results suggest that irradiation mainly causes a decrease in the membrane hydrophobicity through lipid peroxidation. (author)

  15. Liposome Technology for Industrial Purposes

    Directory of Open Access Journals (Sweden)

    Andreas Wagner

    2011-01-01

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

  16. 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.

  17. Novel Nano-Liposome Formulation for Dry Eyes with Components Similar to the Preocular Tear Film

    Directory of Open Access Journals (Sweden)

    Marta Vicario-de-la-Torre

    2018-04-01

    Full Text Available Dry eye is commonly treated with artificial tears; however, developing artificial tears similar to natural tears is difficult due to the complex nature of tears. We characterized and evaluated a novel artificial tear formulation with components similar to the lipid and aqueous constituents of natural tears. Nano-liposomes, composed in part of phosphatidylcholine, were dispersed in an aqueous solution of bioadhesive sodium hyaluronate. Liposome size, zeta potential, and physicochemical properties of the fresh and stored (4 °C liposomal formulation were analyzed. In vitro tolerance was tested using human corneal and conjunctival cell lines by exposures of 15 min to 4 h. The tolerance of the liposomal formulation was evaluated in animals (rabbits. The average liposome size was 186.3 ± 7.0 nm, and the zeta potential was negative. The osmolarity of the formulation was 198.6 ± 1.7 mOsm, with a surface tension of 36.5 ± 0.4 mN/m and viscosity of 3.05 ± 0.02 mPa·s. Viability values in the human corneal and conjunctival cell lines were always >80%, even after liposomal formulation storage for 8 weeks. Discomfort and clinical signs after instillation in rabbit eyes were absent. The new formulation, based on phosphatidylcholine-liposomes dispersed in sodium hyaluronate has suitable components and characteristics, including high in vitro cell viability and good in vivo tolerance, to serve as a tear substitute.

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

    Science.gov (United States)

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

    2017-04-01

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

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

    International Nuclear Information System (INIS)

    Rizos, Apostolos K.; Baritaki, Stavroula; Tsikalas, Ioannis; Doetschman, David C.; Spandidos, Demetrios A.; Krambovitis, Elias

    2007-01-01

    The V3-loop of the HIV-1 gp120 alters host cell immune function and modulates infectivity. We investigated biophysical parameters of liposome constructs with embedded lipopeptides from the principle neutralizing domain of the V3-loop and their influence on viral infectivity. Dynamic light scattering measurements showed liposome supramolecular structures with hydrodynamic radius of the order of 900 and 1300 nm for plain and V3-lipopeptide liposomes. Electron paramagnetic resonance measurements showed almost identical local microenvironment. The difference in liposome hydrodynamic radius was attributed to the fluctuating ionic environment of the V3-lipopeptide liposomes. In vitro HIV-1 infectivity assays showed that plain liposomes reduced virus production in all cell cultures, probably due to the hydrophobic nature of the aggregates. Liposomes carrying V3-lipopeptides with different cationic potentials restored and even enhanced infectivity (p < 0.05). These results highlight the need for elucidation of the involvement of lipid bilayers as dynamic components in supramolecular structures and in HIV-1 fusion mechanisms

  20. The spectral stability of several sunscreening agents on stratum corneum sheets

    NARCIS (Netherlands)

    Kammeyer, A.; Westerhof, W.; Bolhuis, P. A.; Ris, A. J.; Hische, E. A.

    1987-01-01

    Synopsis Film layers of seventeen commercially available sunscreen products and sixteen active ingredients on stratum corneum sheets were spectrophotometrically monitored before and after simulated solar irradiation. Fixed irradiation doses were given within the daily terrestrial limits. From the

  1. Magnetic liposomes based on nickel ferrite nanoparticles for biomedical applications.

    Science.gov (United States)

    Rodrigues, Ana Rita O; Gomes, I T; Almeida, Bernardo G; Araújo, J P; Castanheira, Elisabete M S; Coutinho, Paulo J G

    2015-07-21

    Nickel ferrite nanoparticles with superparamagnetic behavior at room temperature were synthesized using a coprecipitation method. These magnetic nanoparticles were either covered with a lipid bilayer, forming dry magnetic liposomes (DMLs), or entrapped in liposomes, originating aqueous magnetoliposomes (AMLs). A new and promising method for the synthesis of DMLs is described. The presence of the lipid bilayer in DMLs was confirmed by FRET (Förster Resonance Energy Transfer) measurements between the fluorescent-labeled lipids NBD-C12-HPC (NBD acting as a donor) included in the second lipid layer and rhodamine B-DOPE (acceptor) in the first lipid layer. An average donor-acceptor distance of 3 nm was estimated. Assays of the non-specific interactions of magnetoliposomes with biological membranes (modeled using giant unilamellar vesicles, GUVs) were performed. Membrane fusion between both aqueous and dry magnetoliposomes and GUVs was confirmed by FRET, which is an important result regarding applications of these systems both as hyperthermia agents and antitumor drug nanocarriers.

  2. Interactive transport of guanidinylated poly(propylene imine)-based dendrimers through liposomal and cellular membranes.

    Science.gov (United States)

    Tsogas, Ioannis; Sideratou, Zili; Tsiourvas, Dimitris; Theodossiou, Theodossis A; Paleos, Constantinos M

    2007-10-15

    The ability of guanidinylated poly(propylene imine) dendrimers to translocate across lipid bilayers was assessed by employing either a model phosphate-bearing liposomal membrane system or A549 human lung carcinoma cells. Two dendrimer generations, differing in the number of surface guanidinium groups, were employed, while surface acetylation or the use of spacers affected the binding of the guanidinium group to the phosphate moiety and finally the transport efficiency. Following adhesion of dendrimers with liposomes, fusion or transport occurred. Transport through the liposomal bilayer was observed at low guanidinium/phosphate molar ratios, and was enhanced when the bilayer was in the liquid-crystalline phase. For effective transport through the liposomal membrane, an optimum balance between the binding strength and the degree of hydrophobicity of the guanidinylated dendrimer is required. In experiments performed in vitro with cells, efficient penetration and internalization in subcellular organelles and cytosol was observed.

  3. Scattering Studies of Hydrophobic Monomers in Liposomal Bilayers: An Expanding Shell Model of Monomer Distribution

    International Nuclear Information System (INIS)

    Richter, Andrew; Dergunov, Sergey; Ganus, Bill; Thomas, Zachary; Pingali, Sai Venkatesh; Urban, Volker S.; Liu, Yun; Porcar, Lionel; Pinkhassik, Eugene

    2011-01-01

    Hydrophobic monomers partially phase separate from saturated lipids when loaded into lipid bilayers in amounts exceeding a 1:1 monomer/lipid molar ratio. This conclusion is based on the agreement between two independent methods of examining the structure of monomer-loaded bilayers. Complete phase separation of monomers from lipids would result in an increase in bilayer thickness and a slight increase in the diameter of liposomes. A homogeneous distribution of monomers within the bilayer would not change the bilayer thickness and would lead to an increase in the liposome diameter. The increase in bilayer thickness, measured by the combination of small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS), was approximately half of what was predicted for complete phase separation. The increase in liposome diameter, measured by dynamic light scattering (DLS), was intermediate between values predicted for a homogeneous distribution and complete phase separation. Combined SANS, SAXS, and DLS data suggest that at a 1.2 monomer/lipid ratio approximately half of the monomers are located in an interstitial layer sandwiched between lipid sheets. These results expand our understanding of using self-assembled bilayers as scaffolds for the directed covalent assembly of organic nanomaterials. In particular, the partial phase separation of monomers from lipids corroborates the successful creation of nanothin polymer materials with uniform imprinted nanopores. Pore-forming templates do not need to span the lipid bilayer to create a pore in the bilayer-templated films.

  4. Fluorescence quenching of fluorescein by Merocyanine 540 in liposomes

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  5. Protease-Sensitive Liposomes in Chemotherapy & Chemoradiotherapy: From Material Development to In Vivo Application in Tumor-Bearing Mice

    DEFF Research Database (Denmark)

    Brogaard, Rikke Yding; Melander, Fredrik

    to enhance therapeutic efficacies. In this thesis, the development, characterization, and evaluation of an advanced liposomal DDS and its potential in chemoradiotherapy is presented from material development to in vivo application in tumor*bearing mice. In the first part of the thesis, we report the design...... concept of the liposomal DDS, which leads to rapid cellular uptake. Various lipid compositions are tested in uptake and cytotoxicity experiments in vitro, followed by in vivo experiments where the ability of the liposomal DDS to accumulate in tumors together with its anti*cancer activity is explored...... in tumor*bearing mice. The in vivo data demonstrates superior anti*cancer activity relative to the free drug and to conventional, long circulating liposomes. This indicates that the MMP*sensitive liposomal DDS holds potential in therapeutic applications. In the second part of the thesis, the potential...

  6. Applications of lipid nanocarriers for solid tumors therapy: literature review

    International Nuclear Information System (INIS)

    Oliveira, Lidiane Correia de; Souza, Leonardo Gomes; Marreto, Ricardo Neves; Lima, Eliana Martins; Taveira, Stephania Fleury; Taveira, Eliseu Jose Fleury

    2012-01-01

    Introduction: Lipid nanocarriers are systems used to target drugs to its site of action and have attracted attention of the scientific community because they are biocompatible and biodegradable. These systems can target drugs to solid tumors, providing sustained drug release in the site of action, thus increasing the utility of the antineoplastic chemotherapy. Objective: To review the available literature on in vivo experiments with lipid nanocarriers containing cytotoxic drugs for solid tumors treatment. Method: A search study was carried out in Pubmed R database from 2007 to 2011, with subject descriptors: liposomes, lipid nanoparticles, cancer and in vivo, with the boolean operator 'and' among them, in English. Results: 1,595 papers related to the use of liposomes and 77 related to lipid nanoparticles were found. Few studies reported in vivo experiments with lipid nanoparticles (28 papers) compared to liposomes (472 papers), since liposomes were developed two decades before lipid nanoparticles. Four liposomal medicines have already been approved and are used in the clinic while only one medicine containing lipid nanoparticles is in phase I of clinical studies. Conclusion: The number of papers related to the use of nanotechnology for cancer treatment is increasing rapidly, making important to know the different kinds of nanocarriers and, especially, those which are already used in the clinic. There are only few clinical studies on lipid nanocarriers; however, these systems present an enormous potential to improve the clinical practice in oncology. (author)

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

    Directory of Open Access Journals (Sweden)

    Gradauer K

    2012-05-01

    Full Text Available Kerstin Gradauer,1 Caroline Vonach,1 Gerd Leitinger,2,3 Dagmar Kolb,2,3 Eleonore Fröhlich,3 Eva Roblegg,4 Andreas Bernkop-Schnürch,5 Ruth Prassl1,61Institute of Biophysics and Nanosystems Research, Austrian Academy of Sciences, Graz, Austria; 2Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria; 3Center for Medical Research, Medical University of Graz, Graz, Austria; 4Institute of Pharmaceutical Sciences/Pharmaceutical Technology, Karl-Franzens University, Graz, Austria; 5Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria; 6Ludwig Boltzmann Institute for Lung Vascular Research, Graz, AustriaAim: To develop mucoadhesive liposomes by anchoring the polymer chitosan-thioglycolic acid (chitosan-TGA to the liposomal surface to target intestinal mucosal membranes.Methods: Liposomes consisting of phosphatidylcholine (POPC and a maleimide-functionalized lipid were incubated with chitosan-TGA, leading to the formation of a thioether bond between free SH-groups of the polymer and maleimide groups of the liposome. Uncoated and newly generated thiomer-coated liposomes were characterized according to their size, zeta potential, and morphology using photon correlation spectroscopy and transmission electron microscopy. The release behavior of calcitonin and the fluorophore/quencher-couple ANTS/DPX (8-aminonaphthalene-1,3,6-trisulfonic acid/p-xylene-bis- pyridinium bromide from coated and uncoated liposomes, was investigated over 24 hours in simulated gastric and intestinal fluids. To test the mucoadhesive properties of thiomer-coated and uncoated liposomes in-vitro, we used freshly excised porcine small intestine.Results: Liposomes showed a concentration-dependent increase in size – from approximately 167 nm for uncoated liposomes to 439 nm for the highest thiomer concentration used in this study. Likewise, their zeta potentials gradually increased from

  8. Phospholipid liposomes functionalized by protein

    Science.gov (United States)

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

    2015-03-01

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

  9. Defects in Stratum Corneum Desquamation Are the Predominant Effect of Impaired ABCA12 Function in a Novel Mouse Model of Harlequin Ichthyosis.

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    Full Text Available Harlequin Ichthyosis is a severe skin disease caused by mutations in the human gene encoding ABCA12. Here, we characterize a novel mutation in intron 29 of the mouse Abca12 gene that leads to the loss of a 5' splice donor site and truncation of the Abca12 RNA transcript. Homozygous mutants of this smooth skin or smsk allele die perinatally with shiny translucent skin, typical of animal models of Harlequin Ichthyosis. Characterization of smsk mutant skin showed that the delivery of glucosylceramides and CORNEODESMOSIN was defective, while ultrastructural analysis revealed abnormal lamellar bodies and the absence of lipid lamellae in smsk epidermis. Unexpectedly, mutant stratum corneum remained intact when subjected to harsh chemical dissociation procedures. Moreover, both KALLIKREIN 5 and -7 were drastically decreased, with retention of desmoplakin in mutant SC. In cultured wild type keratinocytes, both KALLIKREIN 5 and -7 colocalized with ceramide metabolites following calcium-induced differentiation. Reducing the intracellular levels of glucosylceramide with a glucosylceramide synthase inhibitor resulted in decreased secretion of KALLIKREIN proteases by wild type keratinocytes, but not by smsk mutant keratinocytes. Together, these findings suggest an essential role for ABCA12 in transferring not only lipids, which are required for the formation of multilamellar structures in the stratum corneum, but also proteolytic enzymes that are required for normal desquamation. Smsk mutant mice recapitulate many of the pathological features of HI and can be used to explore novel topical therapies against a potentially lethal and debilitating neonatal disease.

  10. The effect of reticuloendothelial blockade on the blood clearance and tissue distribution of liposomes

    International Nuclear Information System (INIS)

    Souhami, R.L.; Patel, H.M.; Ryman, B.E.

    1981-01-01

    The blood clearance and tissue distribution of liposomes have been studied in mice subjected to reticuloendothelial blockade with dextran sulphate or carbon. The liposomes have been labelled in the lipid membranes with [ 3 H]-cholesterol, [ 14 C]phosphatidylcholine and/or 99 sup(m)Tc and the content with [ 14 C]inulin. Reticuloendothelial blockade has been shown to slow the rate of clearance of neutral, positively and negatively charged liposomes and of both small unilamellar vesicles and large multilamellar vesicles. In normal animals, the liver uptake accounted for only 20-55% of the total injected radioactivity, the amount varying with the charge and size of the liposomes. Following blockade, the liver uptake of charged and neutral multilamellar liposomes was depressed. This was also true for negatively charged small unilamellar vesicles. The degree of depression of hepatic uptake was between 25-50%, which contrasts with the 80-90% reduction in uptake of a wholly phagocytosed particle (sheep red cells). This difference suggets that mechanisms other than Kupffer cell phagocytosis are also responsible for the normal uptake of liposomes into the liver. In the case of neutral and positively charged small unilamellar vesicles, delayed clearance due to blockade was not associated with depressed hepatic uptake. The site of action of blockading agents for these preparations is not clear. With all preparations of liposomes, blockade produced a slight and variable increase in uptake in the lung and spleen. The alteration of distribution of liposomes by reticuloendothelial blockade is therefore not great and the value of the technique in modifying the tissue distribution of substances within liposomes may be limited. (orig.)

  11. Lipid Bilayer Composition Affects Transmembrane Protein Orientation and Function

    Directory of Open Access Journals (Sweden)

    Katie D. Hickey

    2011-01-01

    Full Text Available Sperm membranes change in structure and composition upon ejaculation to undergo capacitation, a molecular transformation which enables spermatozoa to undergo the acrosome reaction and be capable of fertilization. Changes to the membrane environment including lipid composition, specifically lipid microdomains, may be responsible for enabling capacitation. To study the effect of lipid environment on proteins, liposomes were created using lipids extracted from bull sperm membranes, with or without a protein (Na+ K+-ATPase or -amylase. Protein incorporation, function, and orientation were determined. Fluorescence resonance energy transfer (FRET confirmed protein inclusion in the lipid bilayer, and protein function was confirmed using a colourometric assay of phosphate production from ATP cleavage. In the native lipid liposomes, ATPase was oriented with the subunit facing the outer leaflet, while changing the lipid composition to 50% native lipids and 50% exogenous lipids significantly altered this orientation of Na+ K+-ATPase within the membranes.

  12. Light-triggered liposomal cargo delivery platform incorporating photosensitizers and gold nanoparticles for enhanced singlet oxygen generation and increased cytotoxicity

    Science.gov (United States)

    Kautzka, Zofia; Clement, Sandhya; Goldys, Ewa M.; Deng, Wei

    2018-02-01

    We developed light-triggered liposomes incorporating gold nanoparticles and Rose Bengal (RB), a well-known photosensitizer used for photodynamic therapy. Singlet oxygen generated by these liposomes with 532 nm light illumination was characterized by adjusting the molar ratio of lipids and gold nanoparticles while keeping the amount of RB constant. Gold nanoparticles were found to enhance the singlet oxygen generation rate, with a maximum enhancement factor of 1.75 obtained for the molar ratio of HSPC: PE-NH2: gold of 57:5:17 compared with liposomes loaded with RB alone. The experimental results could be explained by the local electric field enhancement caused by gold nanoparticles. We further assessed cellular cytotoxicity of these liposomes by encapsulating an antitumor drug, doxorubicin (Dox); such Dox loaded liposomes were applied to human colorectal cancer cells, HCT116, and exposed to light. Gold-loaded liposomes containing RB and Dox where Dox release was triggered by light were found to exhibit higher cytotoxicity, compared to the liposomes loaded with RB and Dox alone. Our results indicate that gold-loaded liposomes incorporating photosensitizers may have improved therapeutic efficacy in photodynamic therapy and chemotherapy.

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

    Science.gov (United States)

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

    2017-08-07

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

  14. Fusion between fluid liposomes and intact bacteria: study of driving parameters and in vitro bactericidal efficacy

    Directory of Open Access Journals (Sweden)

    Wang Z

    2016-08-01

    Full Text Available Zhao Wang,1,2* Yufan Ma,1,3,4* Hayssam Khalil,1 Rutao Wang,1–3 Tingli Lu,1 Wen Zhao,1 Yang Zhang,3 Jamin Chen,1,2 Tao Chen,1–3  1Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, 2Shaanxi Liposome Research Center, Xi'an, Shaanxi, 3Xi'an Libang Pharmaceuticals Co, Ltd, Xi'an, 4School of Medicine, Xi'an Jiaotong University, Xi'an, People's Republic of China *These authors contributed equally to this work. Background: Pseudomonas aeruginosa represents a good model of antibiotic resistance. These organisms have an outer membrane with a low level of permeability to drugs that is often combined with multidrug efflux pumps, enzymatic inactivation of the drug, or alteration of its molecular target. The acute and growing problem of antibiotic resistance of bacteria to conventional antibiotics made it imperative to develop new liposome formulations for antibiotics, and investigate the fusion between liposome and bacterium. Methods: In this study, the factors involved in fluid liposome interaction with bacteria have been investigated. We also demonstrated a mechanism of fusion between liposomes (1,2-dipalmitoyl-sn-glycero-3-phosphocholine [DPPC]/dimyristoylphosphatidylglycerol [DMPG] 9:1, mol/mol in a fluid state, and intact bacterial cells, by lipid mixing assay. Results: The observed fusion process is shown to be mainly dependent on several key factors. Perturbation of liposome fluidity by addition of cholesterol dramatically decreased the degree of fusion with P. aeruginosa from 44% to 5%. It was observed that fusion between fluid liposomes and bacteria and also the bactericidal activities were strongly dependent upon the properties of the bacteria themselves. The level of fusion detected when fluid liposomes were mixed with Escherichia coli (66% or P. aeruginosa (44% seems to be correlated to their outer membrane phosphatidylethanolamine (PE phospholipids

  15. Structure-transfection activity relationships in a series of novel cationic lipids with heterocyclic head-groups.

    Science.gov (United States)

    Ivanova, Ekaterina A; Maslov, Mikhail A; Kabilova, Tatyana O; Puchkov, Pavel A; Alekseeva, Anna S; Boldyrev, Ivan A; Vlassov, Valentin V; Serebrennikova, Galina A; Morozova, Nina G; Zenkova, Marina A

    2013-11-07

    Cationic liposomes are promising candidates for the delivery of various therapeutic nucleic acids. Here, we report a convenient synthesis of carbamate-type cationic lipids with various hydrophobic domains (tetradecanol, dialkylglycerol, cholesterol) and positively charged head-groups (pyridinium, N-methylimidazolium, N-methylmorpholinium) and data on the structure-transfection activity relationships. It was found that single-chain lipids possess high surface activity, which correlates with high cytotoxicity due to their ability to disrupt the cellular membrane by combined hydrophobic and electrostatic interactions. Liposomes containing these lipids also display high cytotoxicity with respect to all cell lines. Irrespective of chemical structures, all cationic lipids form liposomes with similar sizes and surface potentials. The characteristics of complexes composed of cationic liposomes and nucleic acids depend mostly on the type of nucleic acid and P/N ratios. In the case of oligodeoxyribonucleotide delivery, the transfection activity depends on the type of cationic head-group regardless of the type of hydrophobic domain: all types of cationic liposomes mediate efficient oligonucleotide transfer into 80-90% of the eukaryotic cells, and liposomes based on lipids with N-methylmorpholinium cationic head-group display the highest transfection activity. In the case of plasmid DNA and siRNA, the type of hydrophobic domain determines the transfection activity: liposomes composed of cholesterol-based lipids were the most efficient in DNA transfer, while liposomes containing glycerol-based lipids exhibited reasonable activity in siRNA delivery under serum-free conditions.

  16. Effect of detergents on the physico-chemical properties of skin stratum corneum: A two-photon excitation fluorescence microscopy study

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Brewer, Jonathan R.; Pashkovski, Eugene

    2014-01-01

    OBJECTIVE: Understanding the structural and dynamical features of skin is critical for advancing innovation in personal care and drug discovery. Synthetic detergent mixtures used in commercially available body wash products are thought to be less aggressive towards the skin barrier when compared...... to conventional detergents. The aim of this work is to comparatively characterize the effect of a mild synthetic cleanser mixture (SCM) and sodium dodecyl sulphate (SDS) on the hydration state of the intercellular lipid matrix and on proton activity of excised skin stratum corneum (SC). METHOD: Experiments were...... performed using two-photon excitation fluorescence microscopy. Fluorescent images of fluorescence reporters sensitive to proton activity and hydration of SC were obtained in excised skin and examined in presence and absence of SCM and SDS detergents. RESULTS: Hydration of the intercellular lipid matrix...

  17. Radiation induced peroxidation in model lipid systems

    International Nuclear Information System (INIS)

    Dahlan, K.Z.B.H.M.

    1981-08-01

    In the studies of radiation induced lipid peroxidation, lecithin-liposomes and aqueous micellar solutions of sodium linoleate (or linoleic acid) have been used as models of lipid membrane systems. The liposomes and aqueous linoleate micelles were irradiated in the presence of O 2 and N 2 O/O 2 (80/20 v/v). The peroxidation was initiated using gamma radiation from 60 Co radiation source and was monitored by measuring the increase in absorbance of conjugated diene at 232 nm and by the thiobarbituric acid (TBA) test. The oxidation products were also identified by GLC and GLC-MS analysis. (author)

  18. 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.

  19. 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.

  20. Differences in the stratum corneum of Indonesian infants and adults

    Directory of Open Access Journals (Sweden)

    Tsutomu Fujimura

    2017-02-01

    Full Text Available Background Although understanding the stratum corneum (SC of infant skin is important to avoid skin diseases such as atopic dermatitis, there has been no such investigation in Indonesian infants to date. Objective  To obtain a basic knowledge of SC characteristics in Indonesian infants in order to develop methods for infant-specific skin care and to prevent dermatitis and infection. Methods Seventy-two healthy, full term infants aged 1 to 24 months who were native Indonesians residing in Jakarta were enrolled in this study. Some of the mothers were also enrolled in the study as adults (n=30. Transepidermal water loss (TEWL and hydration of the SC (capacitance on the thigh, buttock, and upper arm were measured after sufficient acclimation in an air-conditioned room, in both infants and mothers. Results The SC hydration was significantly higher in infants than adults at all sites measured, including the buttocks, which is a diaper area. Infant TEWL values were also significantly higher than in adults at all sites. Hydration of the SC and TEWL values showed no significant correlation with age of infant for any site. The SC hydration and TEWL values of Indonesian infants did not decrease to adult values within 24 months, which indicates that the SC characteristics in infants continue to develop after 24 months of age. Conclusion  Indonesian infants aged 0-24 months have significantly higher SC hydration and TEWL values than Indonesian mothers. However, infant age has no correlation to SC hydration or to TEWL values.

  1. Effects of atmospheric relative humidity on Stratum Corneum structure at the molecular level: ex vivo Raman spectroscopy analysis.

    Science.gov (United States)

    Vyumvuhore, Raoul; Tfayli, Ali; Duplan, Hélène; Delalleau, Alexandre; Manfait, Michel; Baillet-Guffroy, Arlette

    2013-07-21

    Skin hydration plays an important role in the optimal physical properties and physiological functions of the skin. Despite the advancements in the last decade, dry skin remains the most common characteristic of human skin disorders. Thus, it is important to understand the effect of hydration on Stratum Corneum (SC) components. In this respect, our interest consists in correlating the variations of unbound and bound water content in the SC with structural and organizational changes in lipids and proteins using a non-invasive technique: Raman spectroscopy. Raman spectra were acquired on human SC at different relative humidity (RH) levels (4-75%). The content of different types of water, bound and free, was measured using the second derivative and curve fitting of the Raman bands in the range of 3100-3700 cm(-1). Changes in lipidic order were evaluated using νC-C and νC-H. To analyze the effect of RH on the protein structure, we examined in the Amide I region, the Fermi doublet of tyrosine, and the νasymCH3 vibration. The contributions of totally bound water were found not to vary with humidity, while partially bound water varied with three different rates. Unbound water increased greatly when all sites for bound water were saturated. Lipid organization as well as protein deployment was found to be optimal at intermediate RH values (around 60%), which correspond to the maximum of SC water binding capacity. This analysis highlights the relationship between bound water, the SC barrier state and the protein structure and elucidates the optimal conditions. Moreover, our results showed that increased content of unbound water in the SC induces disorder in the structures of lipids and proteins.

  2. Cationic liposomal drug delivery system for specific targeting of human cd14+ monocytes in whole blood

    DEFF Research Database (Denmark)

    2013-01-01

    blood when compared to adherence to granulocytes, T-lymphocytes, B- lymphocytes and/or NK cells in freshly drawn blood, to a lipid-based pharmaceutical composition comprising said liposomes and their use in monocytic associated prophylaxis, treatment or amelioration of a condition such as cancer...

  3. Cargo delivery to adhering myoblast cells from liposome-containing poly(dopamine) composite coatings

    DEFF Research Database (Denmark)

    Madsen, Martin Elias Lynge; Mian Teo, Boon; Laursen, Marie Bækgaard

    2013-01-01

    -engineered composite coatings to impose a corresponding cellular response, e.g., a higher amount of embedded liposomes leads to higher uptake efficiency of the fluorescent lipids and cell mean fluorescence or a higher reduction in the viability of the adhering cells. Assessment of the uptake efficiency and cell mean...

  4. Radiation-induced lipid peroxidation: influence of oxygen concentration and membrane lipid composition

    International Nuclear Information System (INIS)

    Wolters, H.; Tilburg, C.A.M. van; Konings, A.W.T.

    1987-01-01

    Radiation -induced lipid peroxidation phospholipid liposomes was investigated in terms of its dependence on lipid composition and oxygen concentration. Non-peroxidizable lipid incorporated in the liposomes reduced the rate of peroxidation of the peroxidizable phospholipid acyl chains, possibly by restricting the length of chain reactions. The latter effect is believed to be caused by interference of the non-peroxidizable lipids in the bilayer. At low oxygen concentration lipid peroxidation was reduced. The cause of this limited peroxidation may be a reduced number of radical initiation reactions possibly involving oxygen-derived superoxide radicals. Killing of proliferating mammalian cells, irradiated at oxygen concentrations ranging from 0 to 100%, appeared to be independent of the concentration of peroxidizable phospholipids in the cell membranes. This indicates that lipid peroxidation is not the determining process in radiation-induced reproductive cell death. (author)

  5. In situ SAXS experiment during DNA and liposome complexation

    Energy Technology Data Exchange (ETDEWEB)

    Gasperini, A.A.; Cavalcanti, L.P. [Laboratorio Nacional de Luz Sincrotron (LNLS), Campinas, SP (Brazil); Balbino, T.A.; Torre, L.G. de la [Universidade Estadual de Campinas (UNICAMP), SP (Brazil); Oliveira, C.L.P. [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil)

    2012-07-01

    Full text: Gene therapy is an exciting research area that allows the treatment of different diseases. Basically, an engineered DNA that codes a protein is the therapeutic drug that has to be delivered to the cell nucleus. After that, the DNA transfection process allows the protein production using the cell machinery. However, the efficient delivery needs DNA protection against nucleases and interstitial fluids. In this context, the use of cationic liposome/DNA complexes is a promising strategy for non-viral gene therapy. Liposomes are lipid systems that self-aggregate in bilayers and the use of cationic lipids allows the electrostatic complexation with DNA. In this work, we used SAXS technique to study the complexation kinetics between cationic liposomes and plasmid DNA and evaluate the liposome structural modifications in the presence of DNA. Liposomes were prepared according to [1] using as plasmid DNA vector model a modified version of pVAX1-GFP with luciferase as reporter gene [2]. The complexation was promoted in a SAXS sample holder containing a microchannel to get access to the compartment between two mica windows where the X-ray beam could cross through [3]. We obtained in situ complexation using such sample holder coupled to a fed-batch reactor through a peristaltic pump. The scattering curves were recorded each 30 seconds during the cycles. The DNA was added until a certain final ratio between surface charges previously determined. We studied the form and structure factor model for the liposome bilayer to fit the scattering curves [4]. Structural information such as the bilayer electronic density profiles, number of bilayers and fluidity were determined as a function of the complexation with DNA. These differences can reflect in singular in vitro and in vivo effects. [1] L. G. de la Torre et al. Colloids and Surfaces B: Biointerfaces, 73, 175 (2009) [2] A. R. Azzoni et al. The Journal of Gene Medicine, 9, 392 (2007) [3] L. P. Cavalcanti et al. Review of

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

    African Journals Online (AJOL)

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

  7. Octanol-assisted liposome assembly on chip

    NARCIS (Netherlands)

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

    2016-01-01

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

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

    Science.gov (United States)

    Suzuki, Ryo; Maruyama, Kazuo

    2010-01-01

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

  9. Temoporfin-loaded liposomes

    DEFF Research Database (Denmark)

    Kuntsche, Judith; Freisleben, Ines; Steiniger, Frank

    2010-01-01

    . 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...

  10. Assay of flippase activity in proteoliposomes using fluorescent lipid derivatives

    DEFF Research Database (Denmark)

    Marek, Magdalena; Günther-Pomorski, Thomas

    2016-01-01

    Specific membrane proteins, termed lipid flippases, play a central role in facilitating the movement of lipids across cellular membranes. In this protocol, we describe the reconstitution of ATP-driven lipid flippases in liposomes and the analysis of their in vitro flippase activity based on the use...... of fluorescent lipid derivatives. Working with purified and reconstituted systems provides a well-defined experimental setup and allows to directly characterize these membrane proteins at the molecular level....

  11. Oleanolic acid liposomes with polyethylene glycol modification: promising antitumor drug delivery

    Directory of Open Access Journals (Sweden)

    Gao D

    2012-07-01

    Full Text Available Dawei Gao, Shengnan Tang, Qi TongApplied Chemical Key Laboratory of Hebei Province, College of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao, ChinaBackground: Oleanolic acid is a pentacyclic triterpene present in many fruits and vegetables, and has received much attention on account of its biological properties. However, its poor solubility and low bioavailability limit its use. The objective of this study was to encapsulate oleanolic acid into nanoliposomes using the modified ethanol injection method.Methods: The liposomes contain a hydrophobic oleanolic acid core, an amphiphilic soybean lecithin monolayer, and a protective hydrophilic polyethylene glycol (PEG coating. During the preparation process, the formulations described were investigated by designing 34 orthogonal experiments as well as considering the effects of different physical characteristics. The four factors were the ratios of drug to soybean phosphatidylcholine (w/w, cholesterol (w/w, PEG-2000 (w/w, and temperature of phosphate-buffered saline at three different levels. We identified the optimized formulation which showed the most satisfactory lipid stability and particle formation. The morphology of the liposomes obtained was determined by transmission electron microscopy and atomic force microscopy. The existence of PEG in the liposome component was validated by Fourier transform infrared spectrum analysis.Results: The PEGylated liposomes dispersed individually and had diameters of around 110–200 nm. Encapsulation efficiency was more than 85%, as calculated by high-performance liquid chromatography and Sephadex® gel filtration. Furthermore, when compared with native oleanolic acid, the liposomal formulations showed better stability in vitro. Finally, the cytotoxicity of the oleanolic acid liposomes was evaluated using a microtiter tetrazolium assay.Conclusion: These results suggest that PEGylated liposomes would serve as a potent delivery vehicle

  12. 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....

  13. Differential scanning calorimetry study on the binding of nucleic acids to dimyristoylphosphatidylcholine-sphingosine liposomes.

    Science.gov (United States)

    Kõiv, A; Mustonen, P; Kinnunen, P K

    1994-03-31

    Binding of DNA and RNA to sphingosine-containing dimyristoylphosphatidylcholine (DMPC) liposomes was characterized by differential scanning calorimetry. The thermal phase behaviour of neat DMPC liposomes was unaffected by the presence of the nucleic acids. However, significant alterations in the melting profiles of the DMPC/sphingosine composite membranes were produced by DNA and RNA, thus revealing their binding to the liposomes. For example, for 79:21 (molar ratio) DMPC/sphingosine liposomes a single endotherm at 29.1 degrees C with an enthalpy of 6.3 kcal/mol lipid was observed. In the presence of DNA at the nucleotide/sphingosine ratio of 0.6 this endotherm separated into three distinct peaks at 28.0, 31.4 and 35.1 degrees C, together with an approximately 22% reduction in the total enthalpy. Further increase in DNA concentration up to 1.5 nucleotides per sphingosine led to complete loss of the original heat absorption peak of the DMPC/sphingosine liposomes, while an endotherm at 34.3 degrees C with delta H of 2.7 kcal/mol developed. By visual inspection, rapid and extensive aggregation of the liposomes due to DNA was evident. Evidence for DNA-induced phase separation was also provided by compression isotherms of sphingosine containing DMPC monolayers recorded over an aqueous buffer both in the presence and absence of DNA. The effects of RNA on the thermal phase behaviour of the composite liposomes were qualitatively similar to those described above for DNA. Notably, the presence of eggPA abolished the nucleic acid induced heat capacity changes for DMPC/sphingosine liposomes probably because of neutralization of the positive charge of sphingosine. The binding of DNA to DMPC/sphingosine liposomes occurred both below and above the lipid phase transition temperature, as shown by fluorescence resonance energy transfer utilizing adriamycin-labelled DNA as a quencher and membrane incorporated pyrene-labelled phospholipid as a donor. However, the apparent binding to

  14. The lipid dependence of melittin action investigated by dual-color fluorescence burst analysis

    NARCIS (Netherlands)

    Bogaart, Geert van den; Mika, Jacek T.; Krasnikov, Viktor; Poolman, Bert

    Dual-color fluorescence-burst analysis was used to study melittin-induced leakage of macromolecules from liposomes of various lipid compositions. To perform dual-color fluorescence-burst analysis, fluorescently labeled size-marker molecules were encapsulated into liposomes, labeled with a second

  15. Role of lipids in the formation and maintenance of the cutaneous permeability barrier.

    Science.gov (United States)

    Feingold, Kenneth R; Elias, Peter M

    2014-03-01

    The major function of the skin is to form a barrier between the internal milieu and the hostile external environment. A permeability barrier that prevents the loss of water and electrolytes is essential for life on land. The permeability barrier is mediated primarily by lipid enriched lamellar membranes that are localized to the extracellular spaces of the stratum corneum. These lipid enriched membranes have a unique structure and contain approximately 50% ceramides, 25% cholesterol, and 15% free fatty acids with very little phospholipid. Lamellar bodies, which are formed during the differentiation of keratinocytes, play a key role in delivering the lipids from the stratum granulosum cells into the extracellular spaces of the stratum corneum. Lamellar bodies contain predominantly glucosylceramides, phospholipids, and cholesterol and following the exocytosis of lamellar lipids into the extracellular space of the stratum corneum these precursor lipids are converted by beta glucocerebrosidase and phospholipases into the ceramides and fatty acids, which comprise the lamellar membranes. The lipids required for lamellar body formation are derived from de novo synthesis by keratinocytes and from extra-cutaneous sources. The lipid synthetic pathways and the regulation of these pathways are described in this review. In addition, the pathways for the uptake of extra-cutaneous lipids into keratinocytes are discussed. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias. Published by Elsevier B.V.

  16. Hyaluronan synthase mediates dye translocation across liposomal membranes

    Directory of Open Access Journals (Sweden)

    Medina Andria P

    2012-01-01

    Full Text Available Abstract Background Hyaluronan (HA is made at the plasma membrane and secreted into the extracellular medium or matrix by phospolipid-dependent hyaluronan synthase (HAS, which is active as a monomer. Since the mechanism by which HA is translocated across membranes is still unresolved, we assessed the presence of an intraprotein pore within HAS by adding purified Streptococcus equisimilis HAS (SeHAS to liposomes preloaded with the fluorophore Cascade Blue (CB. Results CB translocation (efflux was not observed with mock-purified material from empty vector control E. coli membranes, but was induced by SeHAS, purified from membranes, in a time- and dose-dependent manner. CB efflux was eliminated or greatly reduced when purified SeHAS was first treated under conditions that inhibit enzyme activity: heating, oxidization or cysteine modification with N-ethylmaleimide. Reduced CB efflux also occurred with SeHAS K48E or K48F mutants, in which alteration of K48 within membrane domain 2 causes decreased activity and HA product size. The above results used liposomes containing bovine cardiolipin (BCL. An earlier study testing many synthetic lipids found that the best activating lipid for SeHAS is tetraoleoyl cardiolipin (TO-CL and that, in contrast, tetramyristoyl cardiolipin (TM-CL is an inactivating lipid (Weigel et al, J. Biol. Chem. 281, 36542, 2006. Consistent with the effects of these CL species on SeHAS activity, CB efflux was more than 2-fold greater in liposomes made with TO-CL compared to TM-CL. Conclusions The results indicate the presence of an intraprotein pore in HAS and support a model in which HA is translocated to the exterior by HAS itself.

  17. Partitioning of polychlorinated biphenyls into human cells and adipose tissues: evaluation of octanol, triolein, and liposomes as surrogates.

    Science.gov (United States)

    Quinn, Cristina L; van der Heijden, Stephan A; Wania, Frank; Jonker, Michiel T O

    2014-05-20

    Whereas octanol, triacylglycerides, and liposomes have all been proposed as surrogates for measuring the affinity of hydrophobic organic contaminants to human lipids, no comparative evaluation of their suitability exists. Here we conducted batch sorption experiments with polyoxymethylene passive samplers to determine the partition coefficients at 37 °C of 18 polychlorinated biphenyls (PCBs) from water into (i) triolein (Ktriolein/water), (ii) eight types of liposomes (Kliposome/water), (iii) human abdominal fat tissues (KAFT/water) from seven individuals, and (iv) human MCF-7 cells cultured in vitro (Kcell/water). Differences between KAFT/water among individuals and between Kliposome/water among liposome types were very small and not correlated to structural attributes of the PCBs. Similarly, the length and degree of saturation of the phospholipid carbon chains, the headgroup, and the composition of the liposome did not affect the partitioning of PCBs into the studied liposomes. Whereas Kliposome/water values were similar to literature values of Koctanol/water adjusted to 37 °C, they both were lower than KAFT/water and Kcell/water by a factor of 3 on average. Partitioning of PCBs into triolein on the other hand closely mimicked that into human lipids, for which triolein is thus a better surrogate than either octanol or liposomes. Previously published polyparameter linear free energy relationships for partitioning from water into storage lipids and liposomes predicted the measured partition coefficients with a root-mean-square error of less than 0.15 log units, if the chosen equations and solute descriptors do not allow chlorine substitution in the ortho-position to influence the prediction. By guiding the selection of (i) a surrogate for the experimental determination and (ii) a method for the prediction of partitioning into human lipids, this study contributes to a better assessment of hydrophobic organic contaminant bioaccumulation in humans.

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

    Directory of Open Access Journals (Sweden)

    Campos-Martorell M

    2016-06-01

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

  19. Natural moisturizing factor components in the stratum corneum as biomarkers of filaggrin genotype: evaluation of minimally invasive methods

    NARCIS (Netherlands)

    Kezic, S.; Kammeyer, A.; Calkoen, F.; Fluhr, J. W.; Bos, J. D.

    2009-01-01

    Background The carriers of loss-of-function mutations in the filaggrin gene (FLG) have reduced levels of natural moisturizing factor (NMF) in the stratum corneum. The concentration of NMF components which are formed by filaggrin protein breakdown in the stratum corneum might therefore be useful as a

  20. Enhanced Gene Transfer with Fusogenic Liposomes Containing Vesicular Stomatitis Virus G Glycoprotein

    Science.gov (United States)

    Abe, Akihiro; Miyanohara, Atsushi; Friedmann, Theodore

    1998-01-01

    Exposure of Lipofectin-DNA complexes to the partially purified G glycoprotein of the vesicular stomatitis virus envelope (VSV-G) results in loss of serum-mediated inhibition and in enhanced efficiency of gene transfer. Sucrose density gradient sedimentation analysis indicated that the VSV-G associates physically with the DNA-lipid complex to produce a VSV-G liposome. The ability to incorporate surrogate viral or cellular envelope components such as VSV-G into liposomes may allow more-efficient and possibly targeted gene delivery by lipofection, both in vitro and in vivo. PMID:9621082

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

    Directory of Open Access Journals (Sweden)

    Nuno C. Santos

    2002-12-01

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

  2. Liposome-Based Delivery Systems in Plant Polysaccharides

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  3. 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.

  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. 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. Interactions between macromolecule-bound antioxidants and Trolox during liposome autoxidation

    DEFF Research Database (Denmark)

    Celik, Ecem Evrim; Amigo Rubio, Jose Manuel; Andersen, Mogens Larsen

    2017-01-01

    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 Tr...... of logistic function was successfully used for modelling the oxidation curve of liposomes. Principal component analysis revealed two separate phases of liposome autoxidation.......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...... 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...

  7. Effects of various spacers between biotin and the phospholipid headgroup on immobilization and sedimentation of biotinylated phospholipid-containing liposomes facilitated by avidin-biotin interactions.

    Science.gov (United States)

    Sakamoto, Yasuhisa; Kikuchi, Koji; Umeda, Kazuaki; Nakanishi, Hiroyuki

    2017-09-01

    Immobilization and sedimentation of liposomes (lipid vesicles) are used in liposome-protein binding assays, facilitated by avidin/streptavidin/NeutrAvidin and biotinylated phospholipid-containing liposomes. Here, we examined the effects of three spacers [six-carbon (X), polyethylene glycol (PEG) 180 (molecular weight 180) and PEG2000 (molecular weight 2,000)] between biotin and the phospholipid headgroup on the immobilization and sedimentation of small unilamellar liposomes/vesicles (SUVs). PEG180 and PEG2000 showed more efficient immobilization of biotinylated SUVs on NeutrAvidin-coated plates than X, but X and PEG180 showed more efficient sedimentation of biotinylated SUVs upon NeutrAvidin addition than PEG2000. Thus, the most appropriate spacers differed between immobilization and sedimentation. A spacer for biotinylated SUVs must be selected according to the particular liposome-protein binding assays examined. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  8. Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate

    NARCIS (Netherlands)

    de Jongh, Cindy M.; Verberk, Maarten M.; Withagen, Carien E. T.; Jacobs, John J. L.; Rustemeyer, Thomas; Kezic, Sanja

    2006-01-01

    Little is known about cytokines involved in chronic irritant contact dermatitis. Individual cytokine profiles might explain at least part of the differences in the individual response to irritation. Our objective was to investigate the relation between baseline stratum corneum (SC) cytokine levels

  9. Characterization of skin friction coefficient, and relationship to stratum corneum hydration in a normal Chinese population.

    Science.gov (United States)

    Zhu, Y H; Song, S P; Luo, W; Elias, P M; Man, M Q

    2011-01-01

    Studies have demonstrated that some cutaneous biophysical properties vary with age, gender and body sites. However, the characteristics of the skin friction coefficient in different genders and age groups have not yet been well established. In the present study, we assess the skin friction coefficient in a larger Chinese population. A total of 633 subjects (300 males and 333 females) aged 0.15-79 years were enrolled. A Frictiometer FR 770 and Corneometer CM 825 (C&K MPA 5) were used to measure the skin friction coefficient and stratum corneum hydration, respectively, on the dorsal surface of the hand, the forehead and the canthus. In the females, the maximum skin friction coefficients on both the canthus and the dorsal hand skin were observed around the age of 40 years. In the males, the skin friction coefficient on the dorsal hand skin gradually increased from 0 to 40 years of age, and changed little afterward. Skin friction coefficients on some body sites were higher in females than in age-matched males in some age groups. On the canthus and the dorsal hand skin of females, a positive correlation was found between skin friction coefficient and stratum corneum hydration (p skin friction coefficient was positively correlated with stratum corneum hydration on the forehead and the dorsal hand skin (p skin friction coefficient varies with age, gender and body site, and positively correlates with stratum corneum hydration on some body sites. Copyright © 2010 S. Karger AG, Basel.

  10. How Sensitive Are Transdermal Transport Predictions by Microscopic Stratum Corneum Models to Geometric and Transport Parameter Input?

    Science.gov (United States)

    Wen, Jessica; Koo, Soh Myoung; Lape, Nancy

    2018-02-01

    While predictive models of transdermal transport have the potential to reduce human and animal testing, microscopic stratum corneum (SC) model output is highly dependent on idealized SC geometry, transport pathway (transcellular vs. intercellular), and penetrant transport parameters (e.g., compound diffusivity in lipids). Most microscopic models are limited to a simple rectangular brick-and-mortar SC geometry and do not account for variability across delivery sites, hydration levels, and populations. In addition, these models rely on transport parameters obtained from pure theory, parameter fitting to match in vivo experiments, and time-intensive diffusion experiments for each compound. In this work, we develop a microscopic finite element model that allows us to probe model sensitivity to variations in geometry, transport pathway, and hydration level. Given the dearth of experimentally-validated transport data and the wide range in theoretically-predicted transport parameters, we examine the model's response to a variety of transport parameters reported in the literature. Results show that model predictions are strongly dependent on all aforementioned variations, resulting in order-of-magnitude differences in lag times and permeabilities for distinct structure, hydration, and parameter combinations. This work demonstrates that universally predictive models cannot fully succeed without employing experimentally verified transport parameters and individualized SC structures. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  11. Cutaneous water loss and the development of the stratum corneum of nestling house sparrows (Passer domesticus) from desert and mesic environments.

    Science.gov (United States)

    Muñoz-Garcia, Agustí; Williams, Joseph B

    2011-01-01

    Evaporation through the skin contributes to more than half of the total water loss in birds. Therefore, we expect the regulation of cutaneous water loss (CWL) to be crucial for birds, especially those that live in deserts, to maintain a normal state of hydration. Previous studies in adult birds showed that modifications of the lipid composition of the stratum corneum (SC), the outer layer of the epidermis, were associated with changes in rates of CWL. However, few studies have examined the ontogeny of CWL and the lipids of the SC in nestling birds. In this study, we measured CWL and the lipid composition of the SC during development of nestlings from two populations of house sparrows, one from the deserts of Saudi Arabia and the other from mesic Ohio. We found that desert and mesic nestlings followed different developmental trajectories for CWL. Desert nestlings seemed to make a more frugal use of water than did mesic nestlings. To regulate CWL, nestlings appeared to modify the lipid composition of the SC during ontogeny. Our results also suggest a tighter regulation of CWL in desert nestlings, presumably as a result of the stronger selection pressures to which nestlings are exposed in deserts.

  12. Tissue distribution and tumour localization of 99m-technetium-labelled liposomes in cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Richardson, V J; Ryman, B E; Jewkes, R F; Jeyasingh, K; Tattersall, M N.H.; Newlands, E S; Kaye, S B

    1979-07-01

    The possible use of liposomes (Phospholipid vesicles) to direct cytotoxic drugs to tumours led to the investigation of the tissue localization of i.v. injected sup(99m) Tc-labelled liposomes in cancer patients. 20 mg or 300 mg doses of liposomal lipid (7:2:1 molar ratio of phosphatidylcholine: cholesterol: phosphatidic acid) were used in a study of 13 patients with advanced cancer and one with polycythaemia rubra vera (PRV). In all cases except the patient with PRV the major site of uptake of the label was the liver and spleen. In the patient with PRV the liver uptake was greatly reduced and the major site of uptake was found in regions corresponding to marrow. With the exception of one patient with a primary hepatoma, there was no significant tumour uptake of the label.

  13. Liposome-containing Hibiscus sabdariffa calyx extract formulations with increased antioxidant activity, improved dermal penetration and reduced dermal toxicity.

    Science.gov (United States)

    Pinsuwan, Sirirat; Amnuaikit, Thanaporn; Ungphaiboon, Suwipa; Itharat, Arunporn

    2010-12-01

    Hibiscus sabdariffa Linn, or Roselle, is a medicinal plant used extensively in traditional Thai medicine since ancient times. The extracts of Roselle calyces possess antioxidant activity and have potential for development as active ingredients in cosmetic products. However the limitations of using Roselle extracts in cosmetics are its low skin permeation and dermal irritation. Liposome technology is an obvious approach that might overcome these problems. Liposome formulations of standardized Roselle extracts were developed with various lipid components. The formulation showing the highest entrapment efficiency was selected for stability, skin permeation and dermal irritability studies. The liposome formulation with the highest entrapment efficiency (83%) and smalôlest particle size (332 mm) was formulated with phosphatidylcholine from soybean (SPC): Tween 80: deoxycholic acid (DA); 84:16:2.5 weight ratio, total lipid of 200 g/mL and 10% w/v Roselle extract in final liposomal preparation. This liposome formulation was found to be stable after storage at 4 degrees C, protected from light, for 2 months. The in vitro skin permeation studies, using freshly excised pig skin and modified Franz-diffusion cells, showed that the liposome formulation was able to considerably increased the rate of permeation of active compounds in Roselle extracts compared to the Roselle extract solution. The in vivo dermal irritability testing on rabbit skin showed that the liposome formulation dramatically decreased skin irritability compared to the unformulated extract. These results showed that the liposomes containing Roselle extracts had good stability, high entrapment efficacy, increased skin permeation and low skin irritation.

  14. Lipids and skin barrier function - a clinical perspective

    DEFF Research Database (Denmark)

    Jungersted, J.M.; Hellgren, Lars; Jemec, G.B.E.

    2008-01-01

    The stratum corneum (SC) protects us from dehydration and external dangers. Much is known about the morphology of the SC and penetration of drugs through it, but the data are mainly derived from in vitro and animal experiments. In contrast, only a few studies have the human SC lipids as their focus...... and in particular, the role of barrier function in the pathogenesis of skin disease and its subsequent treatment protocols. The 3 major lipids in the SC of importance are ceramides, free fatty acids, and cholesterol. Human studies comparing levels of the major SC lipids in patients with atopic dermatitis...

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

    Science.gov (United States)

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

    2014-01-06

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

  16. 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...

  17. 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

  18. The Role of Cavitation in Liposome Formation

    OpenAIRE

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

    2007-01-01

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

  19. 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

  20. Dual drug delivery using 'smart' liposomes for triggered release of anticancer agents

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Ankit; Gulbake, Arvind; Jain, Ashish; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K., E-mail: drskjainin@yahoo.com [Dr. Hari Singh Gour Vishwavidyalaya, Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences (India)

    2013-07-15

    Ovarian cancer is one of the most fatal gynecologic cancers. In this debut study, dual approach using synergistically active combination of paclitaxel-topotecan (Pac-Top; 20:1, w/w) is investigated with utilization of characteristic features of tumor micro-environment and additionally overexpressed folate receptors (FR-{alpha}) to achieve targeting to tumor site. Various liposomes namely liposomes, PEGylated liposomes, and FR-targeted PEGylated liposomes with lipid compositions viz. DPPC:DMPG (85.5:9.5), DPPC:DMPG:mPEG{sub 2000}-DSPE (85.5:9.5:5), and DPPC:DMPG:mPEG{sub 2000}-DSPE:DSPE-PEG-folate (85.5:9.5:4.5:0.5), respectively, were developed using thin film casting method. These were nanometric in size around 200 nm. In vitro drug release study showed initial burst release followed by sustained release for more than 72 h at physiological milieu (37 {+-} 0.5 Degree-Sign C, pH 7.4) while burst release (i.e., more than 90 %) within 5 min at simulated tumor milieu (41 {+-} 1 Degree-Sign C, pH 4). SRB cytotoxicity assay in OVCAR-3 cell line revealed Pac-Top free (20:1, w/w) to be more toxic (GI{sub 50} = 6.5 {mu}g/ml) than positive control (Adriamycin, GI{sub 50} = 9.1 {mu}g/ml) and FR-targeted PEGylated liposomes GI{sub 50} (14.7 {mu}g/ml). Moreover, florescence microscopy showed the highest cell uptake of FR-targeted PEGylated liposomes so called 'smart liposomes' which has not only mediated effective targeting to FR-{alpha} but also triggered release of drugs upon hyperthermia.

  1. Dual drug delivery using "smart" liposomes for triggered release of anticancer agents

    Science.gov (United States)

    Jain, Ankit; Gulbake, Arvind; Jain, Ashish; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K.

    2013-07-01

    Ovarian cancer is one of the most fatal gynecologic cancers. In this debut study, dual approach using synergistically active combination of paclitaxel-topotecan (Pac-Top; 20:1, w/w) is investigated with utilization of characteristic features of tumor micro-environment and additionally overexpressed folate receptors (FR-α) to achieve targeting to tumor site. Various liposomes namely liposomes, PEGylated liposomes, and FR-targeted PEGylated liposomes with lipid compositions viz. DPPC:DMPG (85.5:9.5), DPPC:DMPG:mPEG2000-DSPE (85.5:9.5:5), and DPPC:DMPG:mPEG2000-DSPE:DSPE-PEG-folate (85.5:9.5:4.5:0.5), respectively, were developed using thin film casting method. These were nanometric in size around 200 nm. In vitro drug release study showed initial burst release followed by sustained release for more than 72 h at physiological milieu (37 ± 0.5 °C, pH 7.4) while burst release (i.e., more than 90 %) within 5 min at simulated tumor milieu (41 ± 1 °C, pH 4). SRB cytotoxicity assay in OVCAR-3 cell line revealed Pac-Top free (20:1, w/w) to be more toxic (GI50 = 6.5 μg/ml) than positive control (Adriamycin, GI50 = 9.1 μg/ml) and FR-targeted PEGylated liposomes GI50 (14.7 μg/ml). Moreover, florescence microscopy showed the highest cell uptake of FR-targeted PEGylated liposomes so called "smart liposomes" which has not only mediated effective targeting to FR-α but also triggered release of drugs upon hyperthermia.

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

    Science.gov (United States)

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

    2011-10-28

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

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

    Directory of Open Access Journals (Sweden)

    Song X

    2017-10-01

    Full Text Available Xiao-li Song,1 Rui-jun Ju,2 Yao Xiao,1 Xin Wang,1 Shuang Liu,1 Min Fu,1 Jing-jing Liu,1 Li-yan Gu,1 Xue-tao Li,1 Lan Cheng1 1School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 2Department of Pharmaceutical Engineering, Beijing Institute of Petrochemical Technology, Beijing, China Abstract: Chemotherapy for aggressive non-small-cell lung cancer (NSCLC usually results in a poor prognosis due to tumor metastasis, vasculogenic mimicry (VM channels, limited killing of tumor cells, and severe systemic toxicity. Herein, we developed a kind of multifunctional targeting epirubicin liposomes to enhance antitumor efficacy for NSCLC. In the liposomes, octreotide was modified on liposomal surface for obtaining a receptor-mediated targeting effect, and honokiol was incorporated into the lipid bilayer for inhibiting tumor metastasis and eliminating VM channels. In vitro cellular assays showed that multifunctional targeting epirubicin liposomes not only exhibited the strongest cytotoxic effect on Lewis lung tumor cells but also showed the most efficient inhibition on VM channels. Action mechanism studies showed that multifunctional targeting epirubicin liposomes could downregulate PI3K, MMP-2, MMP-9, VE-Cadherin, and FAK and activate apoptotic enzyme caspase 3. In vivo results exhibited that multifunctional targeting epirubicin liposomes could accumulate selectively in tumor site and display an obvious antitumor efficacy. In addition, no significant toxicity of blood system and major organs was observed at a test dose. Therefore, multifunctional targeting epirubicin liposomes may provide a safe and efficient therapy strategy for NSCLC. Keywords: octreotide, honokiol, chemotherapy, vasculogenic mimicry, tumor metastasis, targeting drug delivery

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

    Science.gov (United States)

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

    2014-09-01

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

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

  7. A spin labelling study of immunomodulating peptidoglycan monomer and adamantyltripeptides entrapped into liposomes.

    Science.gov (United States)

    Frkanec, Ruza; Noethig-Laslo, Vesna; Vranesić, Branka; Mirosavljević, Krunoslav; Tomasić, Jelka

    2003-04-01

    The interaction of immunostimulating compounds, the peptidoglycan monomer (PGM) and structurally related adamantyltripeptides (AdTP1 and AdTP2), respectively, with phospholipids in liposomal bilayers were investigated by electron paramagnetic resonance spectroscopy. (1). The fatty acids bearing the nitroxide spin label at different positions along the acyl chain were used to investigate the interaction of tested compounds with negatively charged multilamellar liposomes. Electron spin resonance (ESR) spectra were studied at 290 and 310 K. The entrapment of the adamantyltripeptides affected the motional properties of all spin labelled lipids, while the entrapment of PGM had no effect. (2). Spin labelled PGM was prepared and the novel compound bearing the spin label attached via the amino group of diaminopimelic acid was chromatographically purified and chemically characterized. The rotational correlation time of the spin labelled molecule dissolved in buffer at pH 7.4 was studied as a function of temperature. The conformational change was observed above 300 K. The same effect was observed with the spin labelled PGM incorporated into liposomes. Such effect was not observed when the spin labelled PGM was studied at alkaline pH, probably due to the hydrolysis of PGM molecule. The study of possible interaction with liposomal membrane is relevant to the use of tested compounds incorporated into liposomes, as adjuvants in vivo.

  8. Properties of POPC/POPE supported lipid bilayers modified with hydrophobic quantum dots on polyelectrolyte cushions.

    Science.gov (United States)

    Kolasinska-Sojka, Marta; Wlodek, Magdalena; Szuwarzynski, Michal; Kereiche, Sami; Kovacik, Lubomir; Warszynski, Piotr

    2017-10-01

    The formation and properties of supported lipid bilayers (SLB) containing hydrophobic nanoparticles (NP) was studied in relation to underlying cushion obtained from selected polyelectrolyte multilayers. Lipid vesicles were formed from zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and negatively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) in phosphate buffer (PBS). As hydrophobic nanoparticles - quantum dots (QD) with size of 3.8nm (emission wavelength of 420nm) were used. Polyelectrolyte multilayers (PEM) were constructed by the sequential, i.e., layer-by-layer (LbL) adsorption of alternately charged polyelectrolytes from their solutions. Liposomes and Liposome-QDs complexes were studied with Transmission Cryo-Electron Microscopy (Cryo-TEM) to verify the quality of vesicles and the position of QD within lipid bilayer. Deposition of liposomes and liposomes with quantum dots on polyelectrolyte films was studied in situ using quartz crystal microbalance with dissipation (QCM-D) technique. The fluorescence emission spectra were analyzed for both: suspension of liposomes with nanoparticles and for supported lipid bilayers containing QD on PEM. It was demonstrated that quantum dots are located in the hydrophobic part of lipid bilayer. Moreover, we proved that such QD-modified liposomes formed supported lipid bilayers and their final structure depended on the type of underlying cushion. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Investigation of nano lipid vesicles of methotrexate for anti-rheumatoid activity

    Directory of Open Access Journals (Sweden)

    Prabhu P

    2012-01-01

    Full Text Available Prabhakara Prabhu1, Rakshith Shetty1, Marina Koland1, K Vijayanarayana3, KK Vijayalakshmi2, M Harish Nairy1, GS Nisha11Department of Pharmaceutics, Nitte University, NGSM Institute of Pharmaceutical Sciences, Paneer, Deralakatte, Mangalore, Karnataka, India; 2Department of Applied Zoology, Mangalore University, Konaje, Mangalore, Karnataka, India; 3Department of Pharmacy Practice, Manipal University, Manipal College of Pharmaceutical Sciences, Manipal, Karnataka, IndiaBackground: The purpose of this study was to formulate and evaluate nano lipid vesicles of methotrexate (MTX for its anti-rheumatoid activity.Methods: In this study the principle of both active as well as passive targeting using MTX-loaded stealth liposomes as per the magic gun approach was followed. Stealth liposomes of MTX were prepared by thin-film hydration method using a PEGylated phospholipid-like DSPE-MPEG 2000. Similarly, conventional liposomes were prepared using phospholipids like DPPC and DSPC. Conventional liposomes were coated with a hydrophilic biocompatible polymer like chitosan. They were investigated for their physical properties and in vitro release profile. Further, in vivo screening of the formulations for their anti-rheumatoid efficacy was carried out in rats. Rheumatoid arthritis was induced in male Wistar-Lewis rats using complete Freund’s adjuvant (1 mg/mL Mycobacterium tuberculosis, heat killed in mineral oil.Results: It was found that chitosan coating of the conventional liposomes increased the physical stability of the liposomal suspension as well as its entrapment efficiency. The size of the unsonicated lipid vesicles was found to be in the range of 8–10 µm, and the sonicated lipid vesicles in the range of 210–260 nm, with good polydispersity index. Further, chitosan-coated conventional liposomes and the PEGylated liposomes released the drug for a prolonged period of time, compared to the uncoated conventional liposomes. It was found that there

  10. DNA controlled assembly of liposomes

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  11. 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...

  12. Photo-triggered release from liposomes without membrane solubilization, based on binding to poly(vinyl alcohol) carrying a malachite green moiety.

    Science.gov (United States)

    Uda, Ryoko M; Kato, Yutaka; Takei, Michiko

    2016-10-01

    When working with liposomes analogous to cell membranes, it is important to develop substrates that can regulate interactions with the liposome surface in response to light. We achieved a photo-triggered release from liposomes by using a copolymer of poly(vinyl alcohol) carrying a malachite green moiety (PVAMG). Although PVAMG is a neutral polymer under dark conditions, it is photoionized upon exposure to UV light, resulting in the formation of a cationic site for binding to liposomes with a negatively charged surface. Under UV irradiation, PVAMG showed effective interaction with liposomes, releasing the encapsulated compound; however, this release was negligible under dark conditions. The poly(vinyl alcohol) moiety of PVAMG played an important role in the photo-triggered release. This release was caused by membrane destabilization without lipid solubilization. We also investigated different aspects of liposome/PVAMG interactions, including PVAMG-induced fusion between the liposomes and the change in the liposome morphologies. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. The Effect of Polymer Backbone Chemistry on the Induction of the Accelerated Blood Clearance in Polymer Modified Liposomes

    KAUST Repository

    Kierstead, Paul H.

    2015-06-18

    A variety of water-soluble polymers, when attached to a liposome, substantially increase liposome circulation half-life in animals. However, in certain conditions, liposomes modified with the most widely used polymer, polyethylene glycol (PEG), induce an IgM response resulting in an accelerated blood clearance (ABC) of the liposome upon the second injection. Modification of liposomes with other water-soluble polymers: HPMA (poly[N-(2-hydroxypropyl) methacrylamide]), PVP (poly(vinylpyrrolidone)), PMOX (poly(2-methyl-2-oxazoline)), PDMA (poly(N,N-dimethyl acrylamide)), and PAcM (poly(N-acryloyl morpholine)), increase circulation times of liposomes; but a precise comparison of their ability to promote long circulation or induce the ABC effect has not been reported. To obtain a more nuanced understanding of the role of polymer structure/MW to promote long circulation, we synthesized a library of polymer diacyl chain lipids with low polydispersity (1.04-1.09), similar polymer molecular weights (2.1-2.5 kDa) and incorporated them into 100 nm liposomes of a narrow polydispersity (0.25-1.3) composed of polymer-lipid/hydrogenated soy phosphatidylcholine/cholesterol/diD: 5.0/54.5/40/0.5. We confirm that HPMA, PVP, PMOX, PDMA and PAcM modified liposome have increased circulation times in rodents and that PVP, PDMA, PAcM do not induce the ABC effect. We demonstrate for the first time, that HPMA does not cause an ABC effect whereas PMOX induces a pronounced ABC effect in rats. We find that a single dose of liposomes coated with PEG and PMOX generate an IgM response in rats towards the respective polymer. Finally, in this homologous polymer series, we observe a positive correlation (R = 0.84 in rats, R = 0.92 in mice) between the circulation time of polymer-modified liposomes and polymer viscosity; PEG and PMOX, the polymers that can initiate an ABC response were the two most viscous polymers. Our findings suggest that that polymers that do not cause an ABC effect such as, HPMA

  14. The effect of polymer backbone chemistry on the induction of the accelerated blood clearance in polymer modified liposomes.

    Science.gov (United States)

    Kierstead, Paul H; Okochi, Hideaki; Venditto, Vincent J; Chuong, Tracy C; Kivimae, Saul; Fréchet, Jean M J; Szoka, Francis C

    2015-09-10

    A variety of water-soluble polymers, when attached to a liposome, substantially increase liposome circulation half-life in animals. However, in certain conditions, liposomes modified with the most widely used polymer, polyethylene glycol (PEG), induce an IgM response resulting in an accelerated blood clearance (ABC) of the liposome upon the second injection. Modification of liposomes with other water-soluble polymers: HPMA (poly[N-(2-hydroxypropyl) methacrylamide]), PVP (poly(vinylpyrrolidone)), PMOX (poly(2-methyl-2-oxazoline)), PDMA (poly(N,N-dimethyl acrylamide)), and PAcM (poly(N-acryloyl morpholine)), increases circulation times of liposomes; but a precise comparison of their ability to promote long circulation or induce the ABC effect has not been reported. To obtain a more nuanced understanding of the role of polymer structure/MW to promote long circulation, we synthesized a library of polymer diacyl chain lipids with low polydispersity (1.04-1.09), similar polymer molecular weights (2.1-2.5kDa) and incorporated them into 100nm liposomes of a narrow polydispersity (0.25-1.3) composed of polymer-lipid/hydrogenated soy phosphatidylcholine/cholesterol/diD: 5.0/54.5/40/0.5. We confirm that HPMA, PVP, PMOX, PDMA and PAcM modified liposome have increased circulation times in rodents and that PVP, PDMA, and PAcM do not induce the ABC effect. We demonstrate for the first time, that HPMA does not cause an ABC effect whereas PMOX induces a pronounced ABC effect in rats. We find that a single dose of liposomes coated with PEG and PMOX generates an IgM response in rats towards the respective polymer. Finally, in this homologous polymer series, we observe a positive correlation (R=0.84 in rats, R=0.92 in mice) between the circulation time of polymer-modified liposomes and polymer viscosity; PEG and PMOX, the polymers that can initiate an ABC response were the two most viscous polymers. Our findings suggest that polymers that do not cause an ABC effect such as, HPMA or

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2018-02-01

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

  17. Plastic occlusion stress test as a model to investigate the effects of skin delipidization on the stratum corneum water holding capacity in vivo.

    Science.gov (United States)

    Berardesca, E; Herbst, R; Maibach, H

    1993-01-01

    The purpose of the study was to develop an in vivo model to study the effects of lipid removal on skin barrier. 16 subjects (age 41 +/- 8) were delipidized in vivo on the volar forearm using respectively ether/acetone (EA; 1:1) and chloroform/methanol (CM; 2:1). A third site served as control. Water holding capacity (WHC) was measured according to the plastic occlusion stress test (POST) procedure: the water desorption curve after removal of the occlusion was recorded in terms of skin surface water loss (SSWL) using an evaporimeter for 30 min. In the central part of the evaporation curve (bound water) the CM-treated site is significantly different from control and EA-treated sites (p rate of water from SC are higher in the CM-treated site (p evaporation of free water. We conclude that polar lipids have a key role in modulating barrier function and WHC of the stratum corneum. The POST can represent a useful in vivo model to study the effects of lipid extraction on skin function.

  18. 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.

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

    African Journals Online (AJOL)

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

  20. A Dansyl Fluorescence-Based Assay for Monitoring Kinetics of Lipid Extraction and Transfer

    Science.gov (United States)

    Ran, Yong

    2008-01-01

    Lipid transfer proteins (LTPs) play important roles in cellular biology, and fluorescence spectroscopy has found wide range use as a facile means for time-resolved monitoring of protein-lipid interactions[1]. Here, we show how the fluorescence emission properties of dansyl-DHPE can be exploited to characterize lipid extraction and lipid transfer kinetics. The GM2 activator protein serves as an example LTP where the ability to independently characterize lipid extraction from donor vesicles, formation of a protein:lipid complex in solution, and release of lipid from the complex to acceptor liposomes is crucial for full kinetic characterization of lipid transfer. PMID:18694718

  1. Inhibition of growth of human breast cancer cells in culture by neutron capture using liposomes containing 10B.

    Science.gov (United States)

    Yanagië, H; Kobayashi, H; Takeda, Y; Yoshizaki, I; Nonaka, Y; Naka, S; Nojiri, A; Shinnkawa, H; Furuya, Y; Niwa, H; Ariki, K; Yasuhara, H; Eriguchi, M

    2002-03-01

    Cell destruction in boron neutron capture therapy is effected by nuclear reaction between 10B and thermal neutrons with the release of alpha-particles (4He) and lithium-7 ions (7Li). 4He kills cells within 10 microm of the site of 4He generation, therefore it is theoretically possible to destroy tumour cells without affecting adjacent healthy tissue, given selective delivery of compounds containing 10B. Liposomes wore prepared by vortex dispersion of solutions containing 10B compounds with dried lipid films and the effects of those compounds on human breast cancer cells in culture were examined after thermal neutral irradiation. [3H]-TdR incorporation by MRKnu/nu-1 cells treated with 10B-containing liposomes showed 40% suppression compared with liposomes without 10B, at 2 x 1012 n/cm2 thermal neutron fluence. Inhibition of tumour cell growth with liposomes prepared with 100 mm 10B-compound was as significant as with those made with 500 ppm 10B solution. The concentration of 10B in liposomes was 76.5 +/- 3.4 microg/mL. Boronated liposomes can thus deliver sufficient 10B atoms to this line of breast cancer cells in culture to effect cytotoxicity and suppression of growth after thermal neutron irradiation.

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

    Directory of Open Access Journals (Sweden)

    Gabriella Pasaribu

    2016-04-01

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

  3. 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.

  4. Assembly of MreB filaments on liposome membranes: a synthetic biology approach.

    Science.gov (United States)

    Maeda, Yusuke T; Nakadai, Tomoyoshi; Shin, Jonghyeon; Uryu, Kunihiro; Noireaux, Vincent; Libchaber, Albert

    2012-02-17

    The physical interaction between the cytoskeleton and the cell membrane is essential in defining the morphology of living organisms. In this study, we use a synthetic approach to polymerize bacterial MreB filaments inside phospholipid vesicles. When the proteins MreB and MreC are expressed inside the liposomes, the MreB cytoskeleton structure develops at the inner membrane. Furthermore, when purified MreB is used inside the liposomes, MreB filaments form a 4-10 μm rigid bundle structure and deform the lipid vesicles in physical contact with the vesicle inner membrane. These results indicate that the fibrillation of MreB filaments can take place either in close proximity of deformable lipid membrane or in the presence of associated protein. Our finding might be relevant for the self-assembly of cytoskeleton filaments toward the construction of artificial cell systems.

  5. Revisiting the use of sPLA2-sensitive liposomes in cancer therapy

    DEFF Research Database (Denmark)

    Pourhassan, Houman; Clergeaud Veiga, Gael; Hansen, Anders Elias

    2017-01-01

    The first developed secretory phospholipase A2 (sPLA2) sensitive liposomal cisplatin formulation (LiPlaCis®) is currently undergoing clinical evaluation. In the present study we revisit and evaluate critical preclinical parameters important for the therapeutic potential and safety of platinum drugs......, here oxaliplatin (L-OHP), formulated in sPLA2 sensitive liposomes. We show the mole percentage of negatively charged phospholipid needed to obtain enzyme-sensitivity for saturated systems is ≥ 25% for 16-carbon chain lipid membranes, and > 40% for 18-chain lipid membranes, which was surprising as 25......% is used clinically in LiPlaCis®. Efficient sPLA2-dependent growth inhibition of colorectal cancer cells was demonstrated in vitro, where cell membrane degradation and cytolysis depends on the sensitivity of the formulation towards the enzyme and is governed by the amount of lysolipids generated...

  6. Sensitive skin at menopause; dew point and electrometric properties of the stratum corneum.

    Science.gov (United States)

    Paquet, F; Piérard-Franchimont, C; Fumal, I; Goffin, V; Paye, M; Piérard, G E

    1998-01-12

    A number of menopausal women experience skin sensitive to various environmental threats. Two panels of 15 menopausal women on or without HRT were compared. We studied the response of their stratum corneum to variations in environmental humidity, either in air or in response to an emollient. Environment dew point and electrometric measurements on the skin were recorded to search for correlations. Data show that the baseline stratum corneum hydration is influenced by the dew point. HRT improves the barrier function of the skin. The use of emollient further extends the improvement in the functional properties of skin in menopausal women. Both HRT and an emollient can counteract in part some of the deleterious effects of cold and dry weather.

  7. Bactericidal catechins damage the lipid bilayer.

    Science.gov (United States)

    Ikigai, H; Nakae, T; Hara, Y; Shimamura, T

    1993-04-08

    The mode of antibacterial action of, the green tea (Camellia sinensis) extracts, (-)-epigallocatechin gallate (EGCg) and (-)-epicatechin (EC) was investigated. Strong bactericidal EGCg caused leakage of 5,6-carboxyfluorescein from phosphatidylcholine liposomes (PC), but EC with very weak bactericidal activity caused little damage to the membrane. Phosphatidylserine and dicetyl phosphate partially protected the membrane from EGCg-mediated damage when reconstituted into the liposome membrane with PC. EGCg, but not EC, caused strong aggregation and NPN-fluorescence quenching of PC-liposomes and these actions were markedly lowered in the presence of negatively charged lipids. These results show that bactericidal catechins primarily act on and damage bacterial membranes. The observation that Gram-negative bacteria are more resistant to bactericidal catechins than Gram-positive bacteria can be explained to some extent by the presence of negatively charged lipopolysaccharide.

  8. Investigation into the potential chemical mechanism of the pro-oxidant activity of carotenoids with liposomes under UV-irradiation

    Directory of Open Access Journals (Sweden)

    Cvetković Dragan J.

    2017-01-01

    Full Text Available This study focuses on the behavior of β-carotene and lutein inside multilamellar liposomes under continuous UV-irradiation. The liposomes were obtained by the thin film method and carotenoids (Crts were incorporated by mixing at various concentrations (0.005, 0.0075, 0.02, 0.07 and 0.5 mol %. Liposomes formation and the presence of Crts inside them were confirmed by SEM microscopy and FT-IR spectroscopy, respectively. The antioxidant/pro- -oxidant activity of Crts inside liposomes was determined by the thiobarbituric acid–malondialdehyde (TBA–MDA test. The investigated Crts acted more or less unexpected (as pro-oxidants inside the lipid bilayers, interacting with the UV-produced lipid radicals and simultaneously suffering under the UV-irradiation. Their pro-oxidant activity with liposomes and under UV-irradiation could be explained by the formation of unstable adducts in the reaction with peroxyl radicals, or by Crts-cation radicals formation via the electron transfer mechanism. Such tentatively unexpected behavior of carotenoids should be taken into consideration in further carotenoids-based UV-filters projections in cosmetic formulations for skin protection. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. TR-34012

  9. Photo activation of HPPH encapsulated in "Pocket" liposomes triggers multiple drug release and tumor cell killing in mouse breast cancer xenografts.

    Science.gov (United States)

    Sine, Jessica; Urban, Cordula; Thayer, Derek; Charron, Heather; Valim, Niksa; Tata, Darrell B; Schiff, Rachel; Blumenthal, Robert; Joshi, Amit; Puri, Anu

    2015-01-01

    We recently reported laser-triggered release of photosensitive compounds from liposomes containing dipalmitoylphosphatidylcholine (DPPC) and 1,2 bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC(8,9)PC). We hypothesized that the permeation of photoactivated compounds occurs through domains of enhanced fluidity in the liposome membrane and have thus called them "Pocket" liposomes. In this study we have encapsulated the red light activatable anticancer photodynamic therapy drug 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) (Ex/Em410/670 nm) together with calcein (Ex/Em490/517 nm) as a marker for drug release in Pocket liposomes. A mole ratio of 7.6:1 lipid:HPPH was found to be optimal, with >80% of HPPH being included in the liposomes. Exposure of liposomes with a cw-diode 660 nm laser (90 mW, 0-5 minutes) resulted in calcein release only when HPPH was included in the liposomes. Further analysis of the quenching ratios of liposome-entrapped calcein in the laser treated samples indicated that the laser-triggered release occurred via the graded mechanism. In vitro studies with MDA-MB-231-LM2 breast cancer cell line showed significant cell killing upon treatment of cell-liposome suspensions with the laser. To assess in vivo efficacy, we implanted MDA-MB-231-LM2 cells containing the luciferase gene along the mammary fat pads on the ribcage of mice. For biodistribution experiments, trace amounts of a near infrared lipid probe DiR (Ex/Em745/840 nm) were included in the liposomes. Liposomes were injected intravenously and laser treatments (90 mW, 0.9 cm diameter, for an exposure duration ranging from 5-8 minutes) were done 4 hours postinjection (only one tumor per mouse was treated, keeping the second flank tumor as control). Calcein release occurred as indicated by an increase in calcein fluorescence from laser treated tumors only. The animals were observed for up to 15 days postinjection and tumor volume and luciferase expression was measured. A

  10. Photo activation of HPPH encapsulated in “Pocket” liposomes triggers multiple drug release and tumor cell killing in mouse breast cancer xenografts

    Science.gov (United States)

    Sine, Jessica; Urban, Cordula; Thayer, Derek; Charron, Heather; Valim, Niksa; Tata, Darrell B; Schiff, Rachel; Blumenthal, Robert; Joshi, Amit; Puri, Anu

    2015-01-01

    We recently reported laser-triggered release of photosensitive compounds from liposomes containing dipalmitoylphosphatidylcholine (DPPC) and 1,2 bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC8,9PC). We hypothesized that the permeation of photoactivated compounds occurs through domains of enhanced fluidity in the liposome membrane and have thus called them “Pocket” liposomes. In this study we have encapsulated the red light activatable anticancer photodynamic therapy drug 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) (Ex/Em410/670 nm) together with calcein (Ex/Em490/517 nm) as a marker for drug release in Pocket liposomes. A mole ratio of 7.6:1 lipid:HPPH was found to be optimal, with >80% of HPPH being included in the liposomes. Exposure of liposomes with a cw-diode 660 nm laser (90 mW, 0–5 minutes) resulted in calcein release only when HPPH was included in the liposomes. Further analysis of the quenching ratios of liposome-entrapped calcein in the laser treated samples indicated that the laser-triggered release occurred via the graded mechanism. In vitro studies with MDA-MB-231-LM2 breast cancer cell line showed significant cell killing upon treatment of cell-liposome suspensions with the laser. To assess in vivo efficacy, we implanted MDA-MB-231-LM2 cells containing the luciferase gene along the mammary fat pads on the ribcage of mice. For biodistribution experiments, trace amounts of a near infrared lipid probe DiR (Ex/Em745/840 nm) were included in the liposomes. Liposomes were injected intravenously and laser treatments (90 mW, 0.9 cm diameter, for an exposure duration ranging from 5–8 minutes) were done 4 hours postinjection (only one tumor per mouse was treated, keeping the second flank tumor as control). Calcein release occurred as indicated by an increase in calcein fluorescence from laser treated tumors only. The animals were observed for up to 15 days postinjection and tumor volume and luciferase expression was measured. A

  11. The Impact of Bubbles on Measurement of Drug Release from Echogenic Liposomes

    OpenAIRE

    Kopechek, Jonathan A.; Haworth, Kevin J.; Radhakrishnan, Kirthi; Huang, Shaoling; Klegerman, Melvin E.; McPherson, David D.; Holland, Christy K.

    2012-01-01

    Echogenic liposomes (ELIP) encapsulate gas bubbles and drugs within lipid vesicles, but the mechanisms of ultrasound-mediated drug release from ELIP are not well understood. The effect of cavitation activity on drug release from ELIP was investigated in flowing solutions using two fluorescent molecules: a lipophilic drug (rosiglitazone) and a hydrophilic drug substitute (calcein). ELIP samples were exposed to pulsed Doppler ultrasound from a clinical diagnostic ultrasound scanner at pressures...

  12. Cationic liposome-mediated gene transfer to tumor cells in vitro and in vivo.

    Science.gov (United States)

    Son, K; Sorgi, F; Gao, X; Huang, L

    1997-01-01

    Development of safe and effective technology for delivering functional DNA into cells in an intact organism is crucial to broad applications of gene therapy to human disease. Both viral and nonviral vectors have been developed. Of the technologies currently being studied, liposomal delivery system is particularly attractive. Cationic liposome-mediated gene transfection (lipofection), a relatively new technique pioneered by Felgner and coworkers (1), was highly efficient for transfecting cells in culture. The liposomes were composed of an equimolar mixture of a synthetic cationic lipid N-[1-(2,3,-dioleyloxy)propyl]-N,N,N,-trimethylammonium chloride (DOTMA) and a helper lipid dioleoyl-phosphatidylethanolamine (DOPE) Fig. 1). The DOTMA/DOPE mixture (Lipofectin) forms complexes with DNA by charge interaction upon mixing at room temperature. Other catronic lipids are DOTAP, LipofectAMINE, Lipofectam, and DC-chol. The DOTAP is a diester analog of DOTMA and commercially available. LipofectAMINE and Lipofectam are polycationic lipids with a spermine head group that show increased frequency and activity of eukaryotic cell transfection (2,3). 3β-[N-(N',N'-dimethyaminoaminoethane) carbamoyl] cholesterol (DC-chol) (Fig. 1), a cationic cholesterol derivative, was introduced by Gao and Huang (4) and is routinely used in our laboratory. The DC-chol is now commercially available but can be easily synthesized with a single-step reaction from N,N-dimethylethylenediamine and cholesterol chloroformate (4), and improves the efficiency of transfection with minimal toxicity.Liposomes prepared with DC-chol and DOPE (3∶2 molar ratio) are stable at 4°C for at least 1 yr (unpublished data).

  13. Enhanced Ungual Permeation of Terbinafine HCl Delivered Through Liposome-Loaded Nail Lacquer Formulation Optimized by QbD Approach.

    Science.gov (United States)

    Shah, Viral H; Jobanputra, Amee

    2018-01-01

    The present investigation focused on developing, optimizing, and evaluating a novel liposome-loaded nail lacquer formulation for increasing the transungual permeation flux of terbinafine HCl for efficient treatment of onychomycosis. A three-factor, three-level, Box-Behnken design was employed for optimizing process and formulation parameters of liposomal formulation. Liposomes were formulated by thin film hydration technique followed by sonication. Drug to lipid ratio, sonication amplitude, and sonication time were screened as independent variables while particle size, PDI, entrapment efficiency, and zeta potential were selected as quality attributes for liposomal formulation. Multiple regression analysis was employed to construct a second-order quadratic polynomial equation and contour plots. Design space (overlay plot) was generated to optimize a liposomal system, with software-suggested levels of independent variables that could be transformed to desired responses. The optimized liposome formulation was characterized and dispersed in nail lacquer which was further evaluated for different parameters. Results depicted that the optimized terbinafine HCl-loaded liposome formulation exhibited particle size of 182 nm, PDI of 0.175, zeta potential of -26.8 mV, and entrapment efficiency of 80%. Transungual permeability flux of terbinafine HCl through liposome-dispersed nail lacquer formulation was observed to be significantly higher in comparison to nail lacquer with a permeation enhancer. The developed formulation was also observed to be as efficient as pure drug dispersion in its antifungal activity. Thus, it was concluded that the developed formulation can serve as an efficient tool for enhancing the permeability of terbinafine HCl across human nail plate thereby improving its therapeutic efficiency.

  14. 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

  15. Dual drug delivery using “smart” liposomes for triggered release of anticancer agents

    International Nuclear Information System (INIS)

    Jain, Ankit; Gulbake, Arvind; Jain, Ashish; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K.

    2013-01-01

    Ovarian cancer is one of the most fatal gynecologic cancers. In this debut study, dual approach using synergistically active combination of paclitaxel–topotecan (Pac–Top; 20:1, w/w) is investigated with utilization of characteristic features of tumor micro-environment and additionally overexpressed folate receptors (FR-α) to achieve targeting to tumor site. Various liposomes namely liposomes, PEGylated liposomes, and FR-targeted PEGylated liposomes with lipid compositions viz. DPPC:DMPG (85.5:9.5), DPPC:DMPG:mPEG 2000 –DSPE (85.5:9.5:5), and DPPC:DMPG:mPEG 2000 –DSPE:DSPE–PEG–folate (85.5:9.5:4.5:0.5), respectively, were developed using thin film casting method. These were nanometric in size around 200 nm. In vitro drug release study showed initial burst release followed by sustained release for more than 72 h at physiological milieu (37 ± 0.5 °C, pH 7.4) while burst release (i.e., more than 90 %) within 5 min at simulated tumor milieu (41 ± 1 °C, pH 4). SRB cytotoxicity assay in OVCAR-3 cell line revealed Pac–Top free (20:1, w/w) to be more toxic (GI 50 = 6.5 μg/ml) than positive control (Adriamycin, GI 50 = 9.1 μg/ml) and FR-targeted PEGylated liposomes GI 50 (14.7 μg/ml). Moreover, florescence microscopy showed the highest cell uptake of FR-targeted PEGylated liposomes so called “smart liposomes” which has not only mediated effective targeting to FR-α but also triggered release of drugs upon hyperthermia

  16. Renal-targeted delivery of triptolide by entrapment in pegylated TRX-20-modified liposomes.

    Science.gov (United States)

    Yuan, Zhi-Xiang; Jia, Lu; Lim, Lee Yong; Lin, Ju-Chun; Shu, Gang; Zhao, Ling; Ye, Gang; Liang, Xiao-Xia; Ji, Hongming; Fu, Hua-Lin

    2017-01-01

    Previously, 3,5-dipentadecyloxybenzamidine hydrochloride (TRX-20)-modified liposomes were reported to specifically target mesangial cells (MCs) in glomeruli. To further gain a better understanding of the characteristics and potential application for glomerular diseases of TRX-20-modified liposomes, we synthesized TRX-20 and prepared TRX-20-modified liposomes (TRX-LPs) with different molar ratios - 6% (6%-TRX-LP), 11% (11%-TRX-LP), and 14% (14%-TRX-LP) - of TRX-20 to total lipid in the present study. All TRX-LPs exhibited concentration-dependent toxicity against the MCs at a lipid concentration ranging from 0.01 to 1.0 mg/mL with IC 50 values of 3.45, 1.13, and 0.55 mg/mL, respectively. Comparison of the cell viability of TRX-LPs indicated that high levels of TRX-20 caused severe cell mortality, with 11%-TRX-LP showing the higher cytoplasmic accumulation in the MCs. Triptolide (TP) as a model drug was first loaded into 11%-TRX-LP and the liposomes were further modified with PEG 5000 (PEG-TRX-TP-LP) in an attempt to prolong their circulation in blood and enhance TP-mediated immune suppression. Due to specific binding to MCs, PEG-TRX-TP-LP undoubtedly showed better anti-inflammatory action in vitro, evidenced by the inhibition of release of nitric oxide (NO) and tumor necrosis factor-α from lipopolysaccharide-stimulated MCs, compared with free TP at the same dose. In vivo, the PEG-TRX-TP-LP effectively attenuated the symptoms of membranous nephropathic (MN) rats and improved biochemical markers including proteinuria, serum cholesterol, and albumin. Therefore, it can be concluded that the TRX-modified liposome is an effective platform to target the delivery of TP to glomeruli for the treatment of MN.

  17. Drug Delivery Through the Skin: Molecular Simulations of Barrier Lipids to Design more Effective Noninvasive Dermal and Transdermal Delivery Systems for Small Molecules Biologics and Cosmetics

    Energy Technology Data Exchange (ETDEWEB)

    J Torin Huzil; S Sivaloganathan; M Kohandel; M Foldvari

    2011-12-31

    The delivery of drugs through the skin provides a convenient route of administration that is often preferable to injection because it is noninvasive and can typically be self-administered. These two factors alone result in a significant reduction of medical complications and improvement in patient compliance. Unfortunately, a significant obstacle to dermal and transdermal drug delivery alike is the resilient barrier that the epidermal layers of the skin, primarily the stratum corneum, presents for the diffusion of exogenous chemical agents. Further advancement of transdermal drug delivery requires the development of novel delivery systems that are suitable for modern, macromolecular protein and nucleotide therapeutic agents. Significant effort has already been devoted to obtain a functional understanding of the physical barrier properties imparted by the epidermis, specifically the membrane structures of the stratum corneum. However, structural observations of membrane systems are often hindered by low resolutions, making it difficult to resolve the molecular mechanisms related to interactions between lipids found within the stratum corneum. Several models describing the molecular diffusion of drug molecules through the stratum corneum have now been postulated, where chemical permeation enhancers are thought to disrupt the underlying lipid structure, resulting in enhanced permeability. Recent investigations using biphasic vesicles also suggested a possibility for novel mechanisms involving the formation of complex polymorphic lipid phases. In this review, we discuss the advantages and limitations of permeation-enhancing strategies and how computational simulations, at the atomic scale, coupled with physical observations can provide insight into the mechanisms of diffusion through the stratum corneum.

  18. Mechanistic Study of the sPLA2 Mediated Hydrolysis of a Thio-ester Pro Anticancer Ether Lipid

    DEFF Research Database (Denmark)

    Linderoth, Lars; Fristrup, Peter; Hansen, Martin

    2009-01-01

    Secretory phospholipase A2 (sPLA2) is an interesting enzyme for triggered liposomal drug delivery to tumor tissue due the overexpression of sPLA2 in cancerous tissue. A drug delivery system based on the triggered release of therapeutics from sPLA2-sensitive liposomes constituted of pro anticancer...... ether lipids, which become cytotoxic upon sPLA2-catalyzed hydrolysis has previously been established. To optimize the hydrolysis rate of the lipids and thereby optimizing the release profile of the drugs from the liposomes, we have synthesized a thio-ester pro anticancer ether lipid. Liposomes...... constituted of this lipid showed an altered rate of hydrolysis by sPLA2. We have tested the cytotoxicity of the thio-ester pro anticancer ether lipids toward cancer cells, and the results showed that the cytotoxicity is indeed maintained upon sPLA2 exposure. To further understand the origin for the observed...

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

    International Nuclear Information System (INIS)

    Yu, M.D.; Hsieh, D.S.; Huang, W.S.

    2002-01-01

    Aim: Liposomes can provide a gene delivery system to be used in the cancer gene therapy. Radiolabeled liposomes can be used in tumor imaging and tumor therapy. A new cationic liposome formulation of sphingosin e (SP) and dioleoylphosphatidylethanolamine (DOPE) was developed and showed very efficient transfection in a wide variety of mammalian cancer cells, including SKOV-3 (human ovarian carcinoma cells), NPC076 (human nasopharyngeal carcinoma cells), and A431 (human epidermoid carcinoma cells) (Kao et al., Oncol Reports. 5:625-629, 1998). The present study is designed and evaluated the labeling and stability of Tc-99m liposomes by SP/DOPE formulation. Material and Methods: A mixture of 8 mg of SP (Sigma Chemical) and 8 mg of DOPE (Sigma Chemical) dissolved in 4 ml absolute ethanol and used as a lipid stock solution (4 mg/ml). In the direct labeling method, taking 0.25 ml (1 mg) stock solution dried under nitrogen gas and then added 1 ml 20 mM HEPES buffer for hydration 8 hours. The remaining stock solution was dried, hydrated 8 hours, and sonicated 10 min to form liposomes for after-loading labeling method (preformed liposomes). The labeling studies included Tc-99m direct labeling (1), Tc-99m HMPAO direct labeling (2), Tc-99m stannous chloride after-loading labeling (3), Tc-99m HMPAO after-loading labeling (4), and Tc-99m pCMVβ DNA inclusion labeling (5). The labeling efficiency (LE) was determined by thin layer chromatography. The labeled liposomes were incubated with fetal bovine serum (FBS) 30 min to evaluate their stability. Results: It is shown that LE (48%) of Tc-99m direct labeling was the highest in the five methods; however, the LE was reduced to 9% (corrected to original LE) after incubating with serum. Tc-99m may be loosely conjugated to the outer surface of the liposomes. The LE (32%) of Tc-99m HMPAO direct labeling was the second; however, LE was most stable when incubating with serum. The LE of the after-loading labeling was not better than that of

  1. 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.     

  2. Bovine binder-of-sperm protein BSP1 promotes protrusion and nanotube formation from liposomes

    International Nuclear Information System (INIS)

    Lafleur, Michel; Courtemanche, Lesley; Karlsson, Goeran; Edwards, Katarina; Schwartz, Jean-Louis; Manjunath, Puttaswamy

    2010-01-01

    Research highlights: → Binder-of-sperm protein 1 (BSP1) modifies the morphology of lipidic vesicles inducing bead necklace-like and thread-like structures. → In the presence of multilamellar liposomes, BSP1 leads to the formation of long nanotubes. → The insertion of BSP1 in the external lipid leaflet of membranes induces local changes in bilayer curvature. -- Abstract: Binder-of-sperm (BSP) proteins interact with sperm membranes and are proposed to extract selectively phosphatidylcholine and cholesterol from these. This change in lipid composition is a key step in sperm capacitation. The present work demonstrates that the interactions between the protein BSP1 and model membranes composed with phosphatidylcholine lead to drastic changes in the morphology of the lipidic self-assemblies. Using cryo-electron microscopy and fluorescence microscopy, we show that, in the presence of the protein, the lipid vesicles elongate, and form bead necklace-like structures that evolve toward small vesicles or thread-like structures. In the presence of multilamellar vesicles, where a large reservoir of lipid is available, the presence of BSP proteins lead to the formation of long nanotubes. Long spiral-like threads, associated with lipid/protein complexes, are also observed. The local curvature of lipid membranes induced by the BSP proteins may be involved in lipid domain formation and the extraction of some lipids during the sperm maturation process.

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

    Directory of Open Access Journals (Sweden)

    Kuo YC

    2015-04-01

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

  4. Analysis of the 22-NBD-cholesterol transfer between liposome membranes and its relation to the intermembrane exchange of 25-hydroxycholesterol.

    Science.gov (United States)

    Ishii, Haruyuki; Shimanouchi, Toshinori; Umakoshi, Hiroshi; Walde, Peter; Kuboi, Ryoichi

    2010-05-01

    The transfer of 22-NBD-cholesterol (22-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3-ol) between two liposome membranes was quantitatively analyzed by using the fluorescence resonance energy transfer (FRET) method. Liposomes labeled with both 22-NBD-cholesterol and a rhodamine-labeled phosphatidylethanolamine (Rh-DHPE) were used as donor liposomes, and the 22-NBD-cholesterol transfer from these donor liposomes to acceptor liposomes prepared from same type of phosphatidylcholine was monitored. The transfer kinetics was found to be composed of a fast and a slow phase, and all kinetic measurements could be fitted with a bi-exponential model. The results obtained indicate that the 22-NBD-cholesterol transfer kinetics between liposome membranes depends on the fluidity of the liposome used and that the curvature may affect the kinetics. Furthermore, the behavior of 22-NBD-cholesterol in lipid membrane is similar to that of the oxysterol 25-hydroxycholesterol rather than cholesterol. It is proposed that 22-NBD-cholesterol can be a useful fluorescent probe to mimic the intermembrane transfer of oxidized cholesterols like 25-hydroxycholesterol, rather than that of cholesterol itself. 2010 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Hussain A

    2017-07-01

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

  6. 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.

  7. 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

  8. Assembly of the alpha-toxin-hexamer of Staphylococcus aureus in the liposome membrane.

    Science.gov (United States)

    Ikigai, H; Nakae, T

    1987-02-15

    It has been shown that the access of the alpha-toxin of Staphylococcus aureus to the target membrane and assembly of the hexamer can be monitored independently by respectively measuring the fluorescence energy transfer from the tryptophan residue(s) of the toxin to the dansylated phosphatidylethanolamine in the liposome membrane and the fluorescence increment of the toxin at 336 nm (Ikigai, H., and Nakae, T., (1987) J. Biol. Chem. 262, 2150-2155). Measurement of these parameters under various conditions showed the following results: when phosphatidylcholine (PC) liposomes composed of saturated fatty acids were mixed with the toxin, the fluorescence energy transfer occurred below, at, and above the transition temperature of the lipid, but the change of fluorescence at 336 nm was never detectable; when PC-liposomes containing unsaturated fatty acids were used, both the fluorescence energy transfer and the fluorescence increment of 336 nm were observed. These results suggested that the toxin-membrane interaction occurs in PC-membranes containing saturated and/or unsaturated fatty acids and that the oligomerization occurs only in the presence of PC containing unsaturated fatty acid(s). This conclusion was supported by the results of quantitative determination of the toxin-hexamer assembly and leakage of carboxyfluorescein from PC-liposomes under conditions similar to the above.

  9. New Transfection Agents Based on Liposomes Containing Biosurfactant MEL-A.

    Science.gov (United States)

    Nakanishi, Mamoru; Inoh, Yoshikazu; Furuno, Tadahide

    2013-08-16

    Nano vectors are useful tools to deliver foreign DNAs, oligonucleotides, and small interfering double-stranded RNAs (siRNAs) into mammalian cells with gene transfection and gene regulation. In such experiments we have found the liposomes with a biosurfacant mannosylerythriol lipid (MEL-A) are useful because of their high transfer efficiency, and their unique mechanism to transfer genes to target cells with the lowest toxicity. In the present review we will describe our current work, which may contribute to the great advance of gene transfer to target cells and gene regulations. For more than two decades, the liposome technologies have changed dramatically and various methods have been proposed in the fields of biochemistry, cell biology, biotechnology, and so on. In addition, they were towards to pharmaceutics and clinical applications. The liposome technologies were expected to use gene therapy, however, they have not reached a requested goal as of yet. In the present paper we would like to present an approach using a biosurfactant, MEL-A, which is a surface-active compound produced by microorganisms growing on water-insoluble substrates and increases efficiency in gene transfection. The present work shows new transfection agents based on liposomes containing biosurfactant MEL-A.

  10. New Transfection Agents Based on Liposomes Containing Biosurfactant MEL-A

    Directory of Open Access Journals (Sweden)

    Tadahide Furuno

    2013-08-01

    Full Text Available Nano vectors are useful tools to deliver foreign DNAs, oligonucleotides, and small interfering double-stranded RNAs (siRNAs into mammalian cells with gene transfection and gene regulation. In such experiments we have found the liposomes with a biosurfacant mannosylerythriol lipid (MEL-A are useful because of their high transfer efficiency, and their unique mechanism to transfer genes to target cells with the lowest toxicity. In the present review we will describe our current work, which may contribute to the great advance of gene transfer to target cells and gene regulations. For more than two decades, the liposome technologies have changed dramatically and various methods have been proposed in the fields of biochemistry, cell biology, biotechnology, and so on. In addition, they were towards to pharmaceutics and clinical applications. The liposome technologies were expected to use gene therapy, however, they have not reached a requested goal as of yet. In the present paper we would like to present an approach using a biosurfactant, MEL-A, which is a surface-active compound produced by microorganisms growing on water-insoluble substrates and increases efficiency in gene transfection. The present work shows new transfection agents based on liposomes containing biosurfactant MEL-A.

  11. Gd(III)-DOTA-modified sonosensitive liposomes for ultrasound-triggered release and MR imaging

    Science.gov (United States)

    Jung, Suk Hyun; Na, Kyunga; Lee, Seul A.; Cho, Sun Hang; Seong, Hasoo; Shin, Byung Cheol

    2012-08-01

    Ultrasound-sensitive (sonosensitive) liposomes for tumor targeting have been studied in order to increase the antitumor efficacy of drugs and decrease the associated severe side effects. Liposomal contrast agents having Gd(III) are known as a nano-contrast agent system for the efficient and selective delivery of contrast agents into pathological sites. The objective of this study was to prepare Gd(III)-DOTA-modified sonosensitive liposomes (GdSL), which could deliver a model drug, doxorubicin (DOX), to a specific site and, at the same time, be capable of magnetic resonance (MR) imaging. The GdSL was prepared using synthesized Gd(III)-DOTA-1,2-distearoyl- sn-glycero-3-phosphoethanolamine lipid. Sonosensitivity of GdSL to 20-kHz ultrasound induced 33% to 40% of DOX release. The relaxivities ( r 1) of GdSL were 6.6 to 7.8 mM-1 s-1, which were higher than that of MR-bester®. Intracellular uptake properties of GdSL were evaluated according to the intensity of ultrasound. Intracellular uptake of DOX for ultrasound-triggered GdSL was higher than that for non-ultrasound-triggered GdSL. The results of our study suggest that the paramagnetic and sonosensitive liposomes, GdSL, may provide a versatile platform for molecular imaging and targeted drug delivery.

  12. Liposomal curcumin and its application in cancer.

    Science.gov (United States)

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

    2017-01-01

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

  13. Radioprotective effectiveness of Adeturone incapsulated in liposomes

    International Nuclear Information System (INIS)

    Pantev, T.

    1989-01-01

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

  14. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

  16. A study of liposome formation using a solution (isoperibol) calorimeter.

    Science.gov (United States)

    Barriocanal, L; Taylor, K M G; Buckton, G

    2004-12-09

    A solution (isoperibol) calorimeter has been employed to study the process of formation of phospholipid vesicles from natural and synthetic phospholipid films. Phospholipid films were hydrated in the solution calorimeter at temperatures exceeding the main phospholipid phase transition temperature, with continuous agitation to ensure conversion of the hydrating bilayers into multilamellar liposomes. It was seen that retention of chloroform in phospholipid films altered the apparent enthalpy change of vesicle formation to a far greater extent than would be expected from the contribution of the enthalpy of solution of chloroform; this indicates that chloroform alters the hydration process of the lipid. The overall measured enthalpy change for the formation of egg phosphatidylcholine vesicles was exothermic, whilst that for dimyristoylphosphatidylcholine was endothermic. This difference, it is suggested, results from the influence of the hydrocarbon chains mostly on the hydration process and also on the process of vesicle formation.

  17. A Phase of Liposomes with Entangled Tubular Vesicles

    Science.gov (United States)

    Chiruvolu, Shivkumar; Warriner, Heidi E.; Naranjo, Edward; Idziak, Stefan H. J.; Radler, Joachim O.; Plano, Robert J.; Zasadzinski, Joseph A.; Safinya, Cyrus R.

    1994-11-01

    An equilibrium phase belonging to the family of bilayer liposomes in ternary mixtures of dimyristoylphosphatidylcholine (DMPC), water, and geraniol (a biological alcohol derived from oil-soluble vitamins that acts as a cosurfactant) has been identified. Electron and optical microscopy reveal the phase, labeled Ltv, to be composed of highly entangled tubular vesicles. In situ x-ray diffraction confirms that the tubule walls are multilamellar with the lipids in the chain-melted state. Macroscopic observations show that the Ltv phase coexists with the well-known L_4 phase of spherical vesicles and a bulk L_α phase. However, the defining characteristic of the Ltv phase is the Weissenberg rod climbing effect under shear, which results from its polymer-like entangled microstructure.

  18. Use of isothermal titration calorimetry to study the interaction of short-chain alcohols with lipid membranes

    DEFF Research Database (Denmark)

    Trandum, Christa; Westh-Andersen, Peter; Jørgensen, Kent

    1999-01-01

    of short-chain alcohols on Lipid bilayers. isothermal titration calorimetry (ITC) has been used to determine the energy involved in the association of the alcohols with lipid bilayers. Pure unilamellar DMPC liposomes and DMPC liposomes incorporated with different amounts of cholesterol, sphingomyelin...... dependent on the lipid bilayer composition. In the presence of high concentrations of cholesterol, the binding enthalpy of ethanol is decreased, whereas the presence of ceramides enhances the enthalpic response of the lipid bilayer to ethanol. Isothermal titration calorimetry offers a new methodology...

  19. A Thermodynamic Study of the Effects of Cholesterol on the Interaction between Liposomes and Ethanol

    DEFF Research Database (Denmark)

    Trandum, Christa; Westh, Peter; Jørgensen, Kent

    2000-01-01

    The association of ethanol with unilamellar dimyristoyl phosphatidylcholine (DMPC) liposomes of varying cholesterol content has been investigated by isothermal titration calorimetry over a wide temperature range (8-45 degrees C). The calorimetric data show that the interaction of ethanol...... temperature region may play an important role for association of ethanol with the lipid bilayers. Finally, the relation between cholesterol content and the affinity of ethanol for the lipid bilayer provides some support for the in vivo observation that cholesterol acts as a natural antagonist against alcohol...... of ethanol for the lipid bilayer compared to pure DMPC bilayers, whereas higher levels of cholesterol (>10 mol%) reduce affinity of ethanol for the lipid bilayer. Moreover, the experimental data reveal that the affinity of ethanol for the DMPC bilayers containing small amounts of cholesterol is enhanced...

  20. Mechanisms of membrane protein insertion into liposomes during reconstitution procedures involving the use of detergents. 1. Solubilization of large unilamellar liposomes (Prepared by reverse-phase evaporation) by Triton X-100 octyl glucoside, and sodium cholate

    International Nuclear Information System (INIS)

    Paternostre, M.T.; Roux, M.; Rigaud, J.L.

    1988-01-01

    The mechanisms governing the solubilization by Triton X-100, octyl glucoside, and sodium cholate of large unilamellar liposomes prepared by reverse-phase evaporation were investigated. The solubilization process is described by the three-stage model previously proposed for the detergents. In stage I, detergent monomers are incorporated into the phospholipid bilayers until they saturate the liposomes. At this point, i.e., stage II, mixed phospholipid-detergent micelles begin to form. By stage III, the lamellar to micellar transition is complete and all the phospholipids are present as mixed micelles. The turbidity of liposome preparations was systematically measured as a function of the amount of detergent added for a wide range of phospholipid concentrations. The results allowed a quantitative determination of the effective detergent to lipid molar ratios in the saturated liposomes. The monomer concentrations of the three detergents in the aqueous phase were also determined at the lamellar to micellar transitions. These transitions were also investigated by 31 P NMR spectroscopy, and complete agreement was found with turbidity measurements. Freeze-fracture electron microscopy and permeability studies in the sublytic range of detergent concentrations indicated that during stage I of solubilization detergent partitioning between the aqueous phase and the lipid bilayer greatly affects the basic permeability of the liposomes without significantly changing the morphology of the preparations. A rough approximation of the partition coefficients was derived from the turbidity and permeability data. It is concluded that when performed systematically, turbidity measurements constitute a very convenient and powerful technique for the quantitative study of the liposome solubilization process by detergents

  1. 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.

  2. Lipid nanoparticle interactions and assemblies

    Science.gov (United States)

    Preiss, Matthew Ryan

    Novel liposome-nanoparticle assemblies (LNAs) provide a biologically inspired route for designing multifunctional bionanotheranostics. LNAs combine the benefits of lipids and liposomes to encapsulate, transport, and protect hydrophilic and hydrophobic therapeutics with functional nanoparticles. Functional nanoparticles endow LNAs with additional capabilities, including the ability to target diseases, triggered drug release, controlled therapeutic output, and diagnostic capabilities to produce a drug delivery system that can effectively and efficiently deliver therapeutics while reducing side effects. Not only could LNAs make existing drugs better, they could also provide an avenue to allow once promising non-approved drugs (rejected due to harmful side effects, inadequate pharmacokinetics, and poor efficacy) to be safely used through targeted and controlled delivery directly to the diseased site. LNAs have the potential to be stimuli responsive, delivering drugs on command by external (ultrasound, RF heating, etc.) or internal (pH, blood sugar, heart rate, etc.) stimuli. Individually, lipids and nanoparticles have been clinically approved for therapy, such as Doxil (a liposomal doxorubicin for cancer treatment), and diagnosis, such as Feridex (an iron oxide nanoparticle an MRI contrast enhancement agent for liver tumors). In order to engineer these multifunctional LNAs for theranostic applications, the interactions between nanoparticles and lipids must be better understood. This research sought to explore the formation, design, structures, characteristics, and functions of LNAs. To achieve this goal, different types of LNAs were formed, specifically magnetoliposomes, bilayer decorated LNAs (DLNAs), and lipid-coated magnetic nanoparticles (LMNPs). A fluorescent probe was embedded in the lipid bilayer of magnetoliposomes allowing the local temperature and membrane fluidity to be observed. When subjected to an electromagnetic field that heated the encapsulated iron

  3. Incorporation of the purified epstein barr virus/C3d receptor (CR2) into liposomes and demonstration of its dual ligand binding functions

    International Nuclear Information System (INIS)

    Mold, C.; Cooper, N.R.; Nemerow, G.R.

    1986-01-01

    The 145-kDA molecule that has been identified as the C3d receptor CR2 was isolated from lysates of Raji cells by affinity chromatography by using the monoclonal antibody (MoAb)HB-5. The purified protein was incorporated into 14 C-phosphatidylcholine liposomes by deoxycholate dialysis followed by flotation on discontinuous sucrose gradients. Incorporation of the receptor was verified by testing the gradient fractions for CR2 by an enzyme-linked immunosorbent assay. Liposomes were shown to be unilamellar vesicles ranging in diameter from 25 to 100 nm by electron microscopy. The external orientation of CR2 in the membranes was demonstrated by immunoelectron microscopy. The functional activities of liposomes containing CR2 and liposomes without protein were compared. CR2 liposomes bound to EC3d, but not to E, and this binding was inhibited by the anti-CR2 MoAb OKB7 and by a MoAb specific for C3d. Control liposomes failed to bind to either E or EC3D. The ability of CR2 to function as a receptor for Epstein Barr virus (EBV) was tested in two ways. First, CR2 liposomes bound to B95-8, a cell line expressing EBV membrane antigens, but not to B95-8 cells treated with the viral DNA polymerase inhibitor phosphonoformic acid. Second, liposomes containing CR2 were shown by ultracentrifugal analyses to bind directly to purified EBV, and this binding was also inhibited by OKB7. Control liposomes did not bind to B95-8 cells or to EBV. These findings show that CR2 purified from detergent extracts of Raji cells can be reconstituted into lipid membranes with maintenance of its dual functions as a receptor for C3d and EBV

  4. Incorporation of the purified epstein barr virus/C3d receptor (CR2) into liposomes and demonstration of its dual ligand binding functions

    Energy Technology Data Exchange (ETDEWEB)

    Mold, C.; Cooper, N.R.; Nemerow, G.R.

    1986-06-01

    The 145-kDA molecule that has been identified as the C3d receptor CR2 was isolated from lysates of Raji cells by affinity chromatography by using the monoclonal antibody (MoAb)HB-5. The purified protein was incorporated into /sup 14/C-phosphatidylcholine liposomes by deoxycholate dialysis followed by flotation on discontinuous sucrose gradients. Incorporation of the receptor was verified by testing the gradient fractions for CR2 by an enzyme-linked immunosorbent assay. Liposomes were shown to be unilamellar vesicles ranging in diameter from 25 to 100 nm by electron microscopy. The external orientation of CR2 in the membranes was demonstrated by immunoelectron microscopy. The functional activities of liposomes containing CR2 and liposomes without protein were compared. CR2 liposomes bound to EC3d, but not to E, and this binding was inhibited by the anti-CR2 MoAb OKB7 and by a MoAb specific for C3d. Control liposomes failed to bind to either E or EC3D. The ability of CR2 to function as a receptor for Epstein Barr virus (EBV) was tested in two ways. First, CR2 liposomes bound to B95-8, a cell line expressing EBV membrane antigens, but not to B95-8 cells treated with the viral DNA polymerase inhibitor phosphonoformic acid. Second, liposomes containing CR2 were shown by ultracentrifugal analyses to bind directly to purified EBV, and this binding was also inhibited by OKB7. Control liposomes did not bind to B95-8 cells or to EBV. These findings show that CR2 purified from detergent extracts of Raji cells can be reconstituted into lipid membranes with maintenance of its dual functions as a receptor for C3d and EBV.

  5. Radioprotective activity of curcumin-encapsulated liposomes against genotoxicity caused by Gamma Cobalt-60 irradiation in human blood cells.

    Science.gov (United States)

    Nguyen, Minh-Hiep; Pham, Ngoc-Duy; Dong, Bingxue; Nguyen, Thi-Huynh-Nga; Bui, Chi-Bao; Hadinoto, Kunn

    2017-11-01

    While the radioprotective activity of curcumin against genotoxicity has been well established, its poor oral bioavailability has limited its successful clinical applications. Nanoscale formulations, including liposomes, have been demonstrated to improve curcumin bioavailability. The objective of the present work was (1) to prepare and characterize curcumin-encapsulated liposomes (i.e. size, colloidal stability, encapsulation efficiency, and payload), and (2) subsequently to evaluate their radioprotective activity against genotoxicity in human blood cells caused by Gamma Cobalt-60 irradiation. The curcumin-encapsulated liposomes were prepared by lipid-film hydration method using commercial phosphatidylcholine (i.e. Phospholipon ® 90G). The blood cells were obtained from healthy male donors (n = 3) under an approved ethics protocol. The cell uptake and the radioprotective activity of the curcumin-encapsulated liposomes were characterized by fluorescence microscopy and micronucleus assay, respectively. Nanoscale curcumin-encapsulated liposomes exhibiting good physical characteristics and successful uptake by the human blood cells were successfully prepared. The radioprotective activity of the curcumin-encapsulated liposomes was found to be dependent on the curcumin concentration, where an optimal concentration existed (i.e. 30 μg/mL) independent of the irradiation dose, above which the radioprotective activity had become stagnant (i.e. no more reduction in the micronuclei frequency). The present results established for the first time the radioprotective activity of curcumin-encapsulated liposomes in human blood cells, which coupled by its well-established bioavailability, boded well for its potential application as a nanoscale delivery system of other radioprotective phytochemicals.

  6. Potentiating Effects of MPL on DSPC Bearing Cationic Liposomes Promote Recombinant GP63 Vaccine Efficacy: High Immunogenicity and Protection

    Science.gov (United States)

    Mazumder, Saumyabrata; Maji, Mithun; Ali, Nahid

    2011-01-01

    Background Vaccines that activate strong specific Th1-predominant immune responses are critically needed for many intracellular pathogens, including Leishmania. The requirement for sustained and efficient vaccination against leishmaniasis is to formulate the best combination of immunopotentiating adjuvant with the stable antigen (Ag) delivery system. The aim of the present study is to evaluate the effectiveness of an immunomodulator on liposomal Ag through subcutaneous (s.c.) route of immunization, and its usefulness during prime/boost against visceral leishmaniasis (VL) in BALB/c mice. Methodology/Principal Findings Towards this goal, we formulated recombinant GP63 (rGP63)-based vaccines either with monophosphoryl lipid A-trehalose dicorynomycolate (MPL-TDM) or entrapped within cationic liposomes or both. Combinatorial administration of liposomes with MPL-TDM during prime confers activation of dendritic cells, and induces an early robust T cell response. To investigate whether the combined formulation is required for optimum immune response during boost as well, we chose to evaluate the vaccine efficacy in mice primed with combined adjuvant system followed by boosting with either rGP63 alone, in association with MPL-TDM, liposomes or both. We provide evidences that the presence of either liposomal rGP63 or combined formulations during boost is necessary for effective Th1 immune responses (IFN-γ, IL-12, NO) before challenge infection. However, boosting with MPL-TDM in conjugation with liposomal rGP63 resulted in a greater number of IFN-γ producing effector T cells, significantly higher levels of splenocyte proliferation, and Th1 responses compared to mice boosted with liposomal rGP63, after virulent Leishmania donovani (L. donovani) challenge. Moreover, combined formulations offered superior protection against intracellular amastigote replication in macrophages in vitro, and hepatic and splenic parasite load in vivo. Conclusion Our results define the

  7. Development of coated liposomes loaded with ghrelin for nose-to-brain delivery for the treatment of cachexia.

    Science.gov (United States)

    Salade, Laurent; Wauthoz, Nathalie; Deleu, Magali; Vermeersch, Marjorie; De Vriese, Carine; Amighi, Karim; Goole, Jonathan

    2017-01-01

    The aim of the present study was to develop a ghrelin-containing formulation based on liposomes coated with chitosan intended for nose-brain delivery for the treatment of cachexia. Among the three types of liposomes developed, anionic liposomes provided the best results in terms of encapsulation efficiency (56%) and enzymatic protection against trypsin (20.6% vs 0% for ghrelin alone) and carboxylesterase (81.6% vs 17.2% for ghrelin alone). Ghrelin presented both electrostatic and hydrophobic interactions with the anionic lipid bilayer, as demonstrated by isothermal titration calorimetry. Then, anionic liposomes were coated with N -(2-hydroxy) propyl-3-trimethyl ammonium chitosan chloride. The coating involved a size increment from 146.9±2.7 to 194±6.1 nm, for uncoated and coated liposomes, respectively. The ζ-potential was similarly increased from -0.3±1.2 mV to 6±0.4 mV before and after coating, respectively. Chitosan provided mucoadhesion, with an increase in mucin adsorption of 22.9%. Enhancement of permeation through the Calu3 epithelial monolayer was also observed with 10.8% of ghrelin recovered in the basal compartment in comparison to 0% for ghrelin alone. Finally, aerosols generated from two nasal devices (VP3 and SP270) intended for aqueous dispersion were characterized with either coated or uncoated liposomes. Contrarily to the SP270 device, VP3 device showed minor changes between coated and uncoated liposome aerosols, as shown by their median volume diameters of 38.4±5.76 and 37.6±5.74 µm, respectively. Overall, the results obtained in this study show that the developed formulation delivered by the VP3 device can be considered as a potential candidate for nose-brain delivery of ghrelin.

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

    Directory of Open Access Journals (Sweden)

    Xiaobo eFan

    2015-10-01

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

  9. Complement activation-related pseudoallergy in dogs following intravenous administration of a liposomal formulation of meglumine antimoniate

    Directory of Open Access Journals (Sweden)

    Raul R. Ribeiro

    2013-08-01

    Full Text Available The increasing use of nanotechnologies in advanced therapies has allowed the observation of specific adverse reactions related to nanostructures. The toxicity of a novel liposome formulation of meglumine antimoniate in dogs with visceral leishmaniasis after single dose has been investigated. Groups of 12 animals received by the intravenous route a single dose of liposomal meglumine antimoniate (group I [GI], 6.5 mg Sb/kg, empty liposomes (GII or isotonic saline (GIII. Evaluation of hematological and biochemical parameters showed no significant changes 4 days after administration. No undesired effects were registered in the GIII. However, adverse reactions were observed in 67.7% of dogs from both groups that received liposomal formulations. The side effects began moments after bolus administration and disappeared during the first 15 minutes after treatment. Prostation, sialorrhea and defecation were the most frequent clinical signs, registered in 33.3% and 41.6 % of animals from the groups GI and GII, respectively. Tachypnea, mydriasis, miosis, vomiting and cyanosis were also registered in both groups. The adverse reactions observed in this study were attributed to the activation of the complement system by lipid vesicles in a phenomenon known as Complement Activation-Related Pseudoallergy (CARPA. The influence of the physical-chemical characteristics of liposomal formulation in the triggering of CARPA is discussed.

  10. Dynamic Morphological Changes Induced By GM1 and Protein Interactions on the Surface of Cell-Sized Liposomes

    Directory of Open Access Journals (Sweden)

    Masahiro Takagi

    2013-06-01

    Full Text Available It is important to understand the physicochemical mechanisms that are responsible for the morphological changes in the cell membrane in the presence of various stimuli such as osmotic pressure. Lipid rafts are believed to play a crucial role in various cellular processes. It is well established that Ctb (Cholera toxin B subunit recognizes and binds to GM1 (monosialotetrahexosylganglioside on the cell surface with high specificity and affinity. Taking advantage of Ctb-GM1 interaction, we examined how Ctb and GM1 molecules affect the dynamic movement of liposomes. GM1 a natural ligand for cholera toxin, was incorporated into liposome and the interaction between fluorescent Ctb and the liposome was analyzed. The interaction plays an important role in determining the various surface interaction phenomena. Incorporation of GM1 into membrane leads to an increase of the line tension leading to either rupture of liposome membrane or change in the morphology of the membrane. This change in morphology was found to be GM1 concentration specific. The interaction between Ctb-GM1 leads to fast and easy rupture or to morphological changes of the liposome. The interactions of Ctb and the glycosyl chain are believed to affect the surface and the curvature of the membrane. Thus, the results are highly beneficial in the study of signal transduction processes.

  11. Synthesis and in vitro transfection efficiency of spermine-based cationic lipids with different central core structures and lipophilic tails.

    Science.gov (United States)

    Niyomtham, Nattisa; Apiratikul, Nuttapon; Suksen, Kanoknetr; Opanasopit, Praneet; Yingyongnarongkul, Boon-Ek

    2015-02-01

    Twelve spermine-based cationic lipids with four different central core structures (di(oxyethyl)amino, di(oxyethyl)amino carboxy, 3-amino-1,2-dioxypropyl and 2-amino-1,3-dioxypropyl) and three hydrophobic tails (lauric acid, myristic acid and palmitic acid) were synthesized. The liposomes containing lipids and DOPE showed moderate to good in vitro DNA delivery into HeLa cells. GFP expression experiments revealed that liposomes composed of lipids with 3-amino-1,2-dioxypropyl as a central core structure exhibited highest transfection efficiency under serum-free condition. Whereas, lipid with 2-amino-1,3-dioxypropyl core structure showed highest transfection under 10% serum condition. Moreover, the liposomes and lipoplexes composted of these cationic lipids exhibited low cytotoxicity. Copyright © 2015. Published by Elsevier Ltd.

  12. Lipossomas: propriedades físico-químicas e farmacológicas, aplicações na quimioterapia à base de antimônio Liposomes: physicochemical and pharmacological properties, applications in antimony-based chemotherapy

    Directory of Open Access Journals (Sweden)

    Frédéric Frézard

    2005-06-01

    Full Text Available The use of organoantimonial complexes in the therapeutic of leishmaniasis and schistosomiasis has been limited mainly by the need for daily parenteral administration, their adverse side-effects and the appearance of drug resistance. Liposome encapsulation has been so far the most effective means to improve the efficacy of pentavalent antimonials against visceral leishmaniasis. Pharmacologically- and pharmaceutically-acceptable liposomal compositions are still being investigated through manipulation of preparation method, lipid composition and vesicle size. Recently, the encapsulation of a trivalent antimonial within "stealth" liposomes was found to reduce its acute toxicity and effectively deliver this compound to the parasite in experimental schistosomiasis.

  13. A Moessbauer study on the interaction between biomolecular lipid membranes and ferric ferrous ions

    International Nuclear Information System (INIS)

    Karvaly, B.; Badinka, C.; Keszthelyi, L.; Erdei, L.

    1975-01-01

    The results of Moessbauer experiments made on liposome systems of a large specific area are presented. In the study lecithin was used as a membrane-forming material. The measurements were carried out on frozen liposome systems, at various 57 Fe/lipid concentration ratios, pH values and temperatures. Since the presence of liposomes had no noticeable influence on the Moessbauer spectra of Fe 2+ ions, only lecithin Fe 3+ systems were considered. Moessbauer spectra in case of Fe 3+ solutions with lecithin showed marked quadrupole splitting (exhibiting an anomalous temperature dependence) which is not shown in case of pure Fe 3+ solution. (Z.S.)

  14. Nanodiamond decorated liposomes as highly biocompatible delivery vehicles and a comparison with carbon nanotubes and graphene oxide.

    Science.gov (United States)

    Wang, Feng; Liu, Juewen

    2013-12-21

    Studying interactions between nano-carbons and lipid membranes is important for multiplexed drug delivery, device fabrication and for understanding toxicity. Herein, we report that nanodiamond (ND, sp(3) carbon) forms a complex with highly biocompatible zwitterionic liposomes based on hydrogen bonding, which is confirmed by pH-dependent and urea-dependent assays. Despite such weak interaction, the complex is highly stable. Comparisons were made with two sp(2) carbons: nanoscale graphene oxide (NGO) and carbon nanotubes (CNTs), where CNT adsorption is the weakest. Adsorption of the nano-carbons does not induce liposome leakage or affect lipid phase transition temperature. Therefore, the potential toxicity of nano-carbons is unlikely to be related to direct membrane damage. ND facilitates cellular uptake of liposomes and co-delivery of negatively charged calcein and positively charged doxorubicin has been demonstrated. ND has the lowest toxicity, while CNTs and NGO are slightly more toxic. The effect of introducing fusogenic lipids and cholesterol was further studied to understand the effect of lipid formulation.

  15. Astaxanthin Restrains Nitrative-Oxidative Peroxidation in Mitochondrial-Mimetic Liposomes: A Pre-Apoptosis Model

    Science.gov (United States)

    Mano, Camila M.; Cardozo, Karina H. M.; Colepicolo, Pio; Bechara, Etelvino J. H.

    2018-01-01

    Astaxanthin (ASTA) is a ketocarotenoid found in many marine organisms and that affords many benefits to human health. ASTA is particularly effective against radical-mediated lipid peroxidation, and recent findings hypothesize a “mitochondrial-targeted” action of ASTA in cells. Therefore, we examined the protective effects of ASTA against lipid peroxidation in zwitterionic phosphatidylcholine liposomes (PCLs) and anionic phosphatidylcholine: phosphatidylglycerol liposomes (PCPGLs), at different pHs (6.2 to 8.0), which were challenged by oxidizing/nitrating conditions that mimic the regular and preapoptotic redox environment of active mitochondria. Pre-apoptotic conditions were created by oxidized/nitr(osyl)ated cytochrome c and resulted in the highest levels of lipoperoxidation in both PCL and PCPGLs (pH 7.4). ASTA was less protective at acidic conditions, especially in anionic PCPGLs. Our data demonstrated the ability of ASTA to hamper oxidative and nitrative events that lead to cytochrome c-peroxidase apoptosis and lipid peroxidation, although its efficiency changes with pH and lipid composition of membranes. PMID:29649159

  16. ANTISTAPHYLOCOCCAL ACTIVITY OF LIPOSOMAL FORMS OF LINCOMYCIN

    Directory of Open Access Journals (Sweden)

    Derkach SA

    2015-04-01

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

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

    Science.gov (United States)

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

    2016-07-11

    We carried out a mechanistic study to characterize and optimize the remote loading of luciferin into preformed liposomes of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPC/DPPG) 7:3 mixtures. The influence of the loading agent (acetate, propionate, butyrate), the metal counterion (Na(+), K(+), Ca(+2), Mg(+2)), and the initial extra-liposomal amount of luciferin (nL(add)) on the luciferin Loading Efficiency (LE%) and luciferin-to-lipid weight ratio, i.e., Loading Capacity (LC), in the final formulation was determined. In addition, the effect of the loading process on the colloidal stability and phase behavior of the liposomes was monitored. Based on our experimental results, a theoretical model was developed to describe the course of luciferin remote loading. It was found that the highest luciferin loading was obtained with magnesium acetate. The use of longer aliphatic carboxylates or inorganic proton donors pronouncedly reduced luciferin loading, whereas the effect of the counterion was modest. The remote-loading process barely affected the colloidal stability and drug retention of the liposomes, albeit with moderate luciferin-induced membrane perturbations. The correlation between luciferin loading, expressed as LE% and LC, and nL(add) was established, and under our conditions the maximum LC was attained using an nL(add) of around 2.6μmol. Higher amounts of luciferin tend to pronouncedly perturb the liposome stability and luciferin retention. Our theoretical model furnishes a fair quantitative description of the correlation between nL(add) and luciferin loading, and a membrane permeability coefficient for uncharged luciferin of 1×10(-8)cm/s could be determined. We believe that our study will prove very useful to optimize the remote-loading strategies of moderately polar carboxylic acid drugs in general. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  19. Epiphytic flora on Gelidium corneum (Rhodophyta: Gelidiales in relation to wave exposure and depth

    Directory of Open Access Journals (Sweden)

    Endika Quintano

    2015-12-01

    Full Text Available The canopy-forming macroalga Gelidium corneum (Hudson J.V. Lamouroux plays a major role in the functioning of the subtidal ecosystem of the Cantabrian Sea (northern Spain. Despite its importance, little is known about the factors that may potentially affect the distribution pattern of its epiphytic flora. Here we examine two indirect factors: coastal orientation (N and NW and depth (3 and 7 m, as proxies for wave exposure and light availability, respectively. We test their effects on the total epiphytic load, alpha diversity (species richness, Shannon, Simpson and evenness measures and multivariate structure of the epiphytic flora growing on G. corneum in subtidal waters off the Basque coast. Plocamium cartilagineum, Dictyota dichotoma and Acrosorium ciliolatum were found to be the most common epiphytes. Significant interactive effect of coastal orientation and depth were observed for species composition and abundance of epiphytic flora. Increased wave exposure resulted in a lower epiphyte load and a less diverse community, suggesting that under high hydrodynamic conditions epiphytes were more likely to become dislodged from hosts. However, light availability only had a significant effect on the distribution of epiphytes below a certain threshold of wave action, with the epiphytic load being 30-40% greater on shallow bottoms.

  20. Incomplete KLK7 Secretion and Upregulated LEKTI Expression Underlie Hyperkeratotic Stratum Corneum in Atopic Dermatitis.

    Science.gov (United States)

    Igawa, Satomi; Kishibe, Mari; Minami-Hori, Masako; Honma, Masaru; Tsujimura, Hisashi; Ishikawa, Junko; Fujimura, Tsutomu; Murakami, Masamoto; Ishida-Yamamoto, Akemi

    2017-02-01

    Atopic dermatitis (AD) is a common inflammatory skin disorder. Chronic AD lesions present hyperkeratosis, indicating a disturbed desquamation process. KLK7 is a serine protease involved in the proteolysis of extracellular corneodesmosome components, including desmocollin 1 and corneodesmosin, which leads to desquamation. KLK7 is secreted by lamellar granules and upregulated in AD lesional skin. However, despite increased KLK7 protein levels, immunostaining and electron microscopy indicated numerous corneodesmosomes remaining in the uppermost layer of the stratum corneum from AD lesions. We aimed to clarify the discrepancy between KLK7 overexpression and retention of corneodesmosomes on AD corneocytes. Western blot analysis indicated abnormal corneodesmosin degradation patterns in stratum corneum from AD lesions. The KLK activity of tape-stripped corneocytes from AD lesions was not significantly elevated in in situ zymography, which was our new attempt to detect the protease activity more precisely than conventional assays. This ineffective KLK activation was associated with impaired KLK7 secretion from lamellar granules and increased expression of LEKTI in AD. Such imbalances in protease-protease inhibitor interactions could lead to abnormal proteolysis of corneodesmosomes and compact hyperkeratosis. Upregulated expression of LEKTI might be a compensatory mechanism to prevent further barrier dysfunction in AD. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Investigation of the cosmetic ingredient distribution in the stratum corneum using NanoSIMS imaging

    International Nuclear Information System (INIS)

    Tanji, N.; Okamoto, M.; Katayama, Y.; Hosokawa, M.; Takahata, N.; Sano, Y.

    2008-01-01

    In order to understand the mechanisms of action of cosmetic ingredients, it is important to establish the distribution of the component agents within the epidermis of the skin. To date, time-of-flight secondary ion mass spectrometry (TOF-SIMS) has been used to detect cosmetic ingredients in the skin. However, it is technically difficult to investigate the distribution of the agents in the stratum corneum using TOF-SIMS. Therefore, an analytical method with higher spatial resolution is required. In this study, we investigated an imaging analysis technique based on NanoSIMS to detect cosmetic ingredients in the skin. Pig skin was used as a model for human skin. The sample was treated with a cosmetic formulation containing 15 N-labelled pseudo-ceramide (SLE). The sample was frozen with liquid nitrogen and cross-sections were cut using a cryomicrotome. As a result, the fine layer structure of the corneocytes was clearly observed by using NanoSIMS. Our studies indicate that SLE penetrates into the stratum corneum via an intercellular route. We conclude that application of NanoSIMS analysis can contribute to a better understanding of the function of cosmetic ingredients in the skin.

  2. Systemic study of solvent-assisted active loading of gambogic acid into liposomes and its formulation optimization for improved delivery.

    Science.gov (United States)

    Tang, Wei-Lun; Tang, Wei-Hsin; Szeitz, Andras; Kulkarni, Jayesh; Cullis, Pieter; Li, Shyh-Dar

    2018-06-01

    The solvent-assisted active loading technology (SALT) was developed for encapsulating a water insoluble weak base into the liposomal core in the presence of 5% DMSO. In this study, we further examined the effect of various water miscible solvents in promoting active loading of other types of drugs into liposomes. To achieve complete drug loading, the amount of solvent required must result in complete drug solubilization and membrane permeability enhancement, but must be below the threshold that induces liposomal aggregation or causes bilayer disruption. We then used the SALT to load gambogic acid (GA, an insoluble model drug that shows promising anticancer effect) into liposomes, and optimized the loading gradient and lipid composition to prepare a stable formulation (Lipo-GA) that displayed >95% drug retention after incubation with serum for 3 days. Lipo-GA contained a high drug-to-lipid ratio of 1/5 (w/w) with a mean particle size of ∼75 nm. It also displayed a prolonged circulation half-life (1.5 h vs. 18.6 h) and enhanced antitumor activity in two syngeneic mice models compared to free GA. Particularly, complete tumor regression was observed in the EMT6 tumor model for 14 d with significant inhibition of multiple oncogenes including HIF-1α, VEGF-A, STAT3, BCL-2, and NF-κB. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Usefulness of liposomes carrying losefamate for CT opacification of liver and spleen

    International Nuclear Information System (INIS)

    Seltzer, S.E.; Shulkin, P.M.; Adams, D.F.; Davis, M.A.; Hoey, G.B.; Hopkins, R.M.; Bosworth, M.E.

    1984-01-01

    Iosefamate, a hepatobiliary contrast agent, was encapsulated into liposomes to increase its ability to opacify the liver and spleen on computed tomographic (CT) images. Multilamellar lipid vesicles containing iosefamate in their aqueous phase were prepared. Seven dogs received intravenous injections of 100-300 mg l/kg in one of three forms; encapsulated, unencapsulated, or a mixture of the two in equal parts. Animals that received the opaque vesicles had marked opacification of their livers, bile ducts, gallbladders, spleens and gastrointestinal tracts. At the high-dose level, liver upake of the encapsulated materials was also greater. Liposome-encapsulated hepatobiliary contrast agents are effective liver and spleen opacifiers for CT imaging in the dog

  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. Amperometric Adhesion Signals of Liposomes, Cells and Droplets

    OpenAIRE

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

    2009-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ingemann Jensen, A.T.

    2013-06-01

    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 reference list is compiled in the end, immediately after the three chapters. This is followed by the supplementary information, divided into appropriate sections. Finally, the two first-authored manuscripts are attached as appendices. Chapter 1. The field of nanoparticulate drug delivery has been hailed 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, that self-assemble in water. Therapy with nanoparticles is hampered by often poor tumor accumulation, combined with massive uptake by macrophages in the liver and spleen. For this reason, visualizing nanoparticle pharmacokinetics in-vivo is a valuable tool in the on-going research. Such visualization can be done by labeling with radio isotopes. Isotopes that emit positrons (PET-isotopes) can be detected by PET (positron emission tomography) technology, an accurate technique that has gained popularity in recent years. PET-isotopes of interest include 18F and 64Cu. In addition to being a research tool, radiolabeled nanoparticles hold promise as a radiopharmaceutical in themselves, as a means of imaging tumor tissue, aiding in diagnosis and surgery. Chapter 2. A method for labeling liposomes with 18F (97% positron decay, T = 110 min) was investigated. 18F is widely available, but is hampered by a short half-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

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

    International Nuclear Information System (INIS)

    Ingemann Jensen, A.T.

    2013-01-01

    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 reference list is compiled in the end, immediately after the three chapters. This is followed by the supplementary information, divided into appropriate sections. Finally, the two first-authored manuscripts are attached as appendices. Chapter 1. The field of nanoparticulate drug delivery has been hailed 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, that self-assemble in water. Therapy with nanoparticles is hampered by often poor tumor accumulation, combined with massive uptake by macrophages in the liver and spleen. For this reason, visualizing nanoparticle pharmacokinetics in-vivo is a valuable tool in the on-going research. Such visualization can be done by labeling with radio isotopes. Isotopes that emit positrons (PET-isotopes) can be detected by PET (positron emission tomography) technology, an accurate technique that has gained popularity in recent years. PET-isotopes of interest include 18F and 64Cu. In addition to being a research tool, radiolabeled nanoparticles hold promise as a radiopharmaceutical in themselves, as a means of imaging tumor tissue, aiding in diagnosis and surgery. Chapter 2. A method for labeling liposomes with 18F (97% positron decay, T = 110 min) was investigated. 18F is widely available, but is hampered by a short half-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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  10. 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 ...

  11. 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 ...

  12. Liposomal curcumin and its application in cancer

    Directory of Open Access Journals (Sweden)

    Feng T

    2017-08-01

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

  13. Treatment of Digital Ischemia with Liposomal Bupivacaine

    Directory of Open Access Journals (Sweden)

    José Raul Soberón

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-06-28

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

  15. 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

  16. Imaging of blood plasma coagulation at supported lipid membranes.

    Science.gov (United States)

    Faxälv, Lars; Hume, Jasmin; Kasemo, Bengt; Svedhem, Sofia

    2011-12-15

    The blood coagulation system relies on lipid membrane constituents to act as regulators of the coagulation process upon vascular trauma, and in particular the 2D configuration of the lipid membranes is known to efficiently catalyze enzymatic activity of blood coagulation factors. This work demonstrates a new application of a recently developed methodology to study blood coagulation at lipid membrane interfaces with the use of imaging technology. Lipid membranes with varied net charges were formed on silica supports by systematically using different combinations of lipids where neutral phosphocholine (PC) lipids were mixed with phospholipids having either positively charged ethylphosphocholine (EPC), or negatively charged phosphatidylserine (PS) headgroups. Coagulation imaging demonstrated that negatively charged SiO(2) and membrane surfaces exposing PS (obtained from liposomes containing 30% of PS) had coagulation times which were significantly shorter than those for plain PC membranes and EPC exposing membrane surfaces (obtained from liposomes containing 30% of EPC). Coagulation times decreased non-linearly with increasing negative surface charge for lipid membranes. A threshold value for shorter coagulation times was observed below a PS content of ∼6%. We conclude that the lipid membranes on solid support studied with the imaging setup as presented in this study offers a flexible and non-expensive solution for coagulation studies at biological membranes. It will be interesting to extend the present study towards examining coagulation on more complex lipid-based model systems. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Formation of supported lipid bilayers of charged E. coli lipids on modified gold by vesicle fusion

    Directory of Open Access Journals (Sweden)

    Ileana F. Márquez

    2017-01-01

    Full Text Available We describe a simple way of fusing E. coli lipid vesicles onto a gold surface. Supported lipid bilayers on metal surfaces are interesting for several reasons: transducing a biological signal to an electric readout, using surface analytical tools such as Surface Plasmon Resonance (SPR, Infrared Reflection Absorption Spectroscopy, Neutron Reflectivity or Electrochemistry. The most widely used method to prepare supported lipid membranes is fusion of preexisting liposomes. It is quite efficient on hydrophilic surfaces such as glass, mica or SiO2, but vesicle fusion on metals and metal oxide surfaces (as gold, titanium oxide or indium tin oxide, remains a challenge, particularly for vesicles containing charged lipids, as is the case of bacterial lipids. We describe a simple method based on modifying the gold surface with a charged mercaptopropionic acid self-assembled monolayer and liposomes partially solubilized with detergent. The formed bilayers were characterized using a Quartz Crystal Microbalance with dissipation (QCM-D and Atomic Force Microscopy (AFM. Some advantages of this protocol are that the stability of the self-assembled monolayer allows for repeated use of the substrate after detergent removal of the bilayer and that the amount of detergent required for optimal fusion can be determined previously using the lipid-detergent solubility curve.

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

    NARCIS (Netherlands)

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

    1998-01-01

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

  19. Proton permeation of lipid bilayers.

    Science.gov (United States)

    Deamer, D W

    1987-10-01

    Proton permeation of the lipid bilayer barrier has two unique features. First, permeability coefficients measured at neutral pH ranges are six to seven orders of magnitude greater than expected from knowledge of other monovalent cations. Second, proton conductance across planar lipid bilayers varies at most by a factor of 10 when pH is varied from near 1 to near 11. Two mechanisms have been proposed to account for this anomalous behavior: proton conductance related to contaminants of lipid bilayers, and proton translocation along transient hydrogen-bonded chains (tHBC) of associated water molecules in the membrane. The weight of evidence suggests that trace contaminants may contribute to proton conductance across planar lipid membranes at certain pH ranges, but cannot account for the anomalous proton flux in liposome systems. Two new results will be reported here which were designed to test the tHBC model. These include measurements of relative proton/potassium permeability in the gramicidin channel, and plots of proton flux against the magnitude of pH gradients. (1) The relative permeabilities of protons and potassium through the gramicidin channel, which contains a single strand of hydrogen-bonded water molecules, were found to differ by at least four orders of magnitude when measured at neutral pH ranges. This result demonstrates that a hydrogen-bonded chain of water molecules can provide substantial discrimination between protons and other cations. It was also possible to calculate that if approximately 7% of bilayer water was present in a transient configuration similar to that of the gramicidin channel, it could account for the measured proton flux. (2) The plot of proton conductance against pH gradient across liposome membranes was superlinear, a result that is consistent with one of three alternative tHBC models for proton conductance described by Nagle elsewhere in this volume.

  20. Radioprotective effectiveness of Adeturone, incapsulated in liposomes

    International Nuclear Information System (INIS)

    Pantev, T.

    1990-01-01

    The radioprotective properties of Adeturone (S,2-aminoethyl isothiuronic adenosine-5-triphosphate), incapsulated in mono- and tricomponent lisosomes was studied. Intraperitoneal adminisration of the radioprotector by means of monocomponent liposomes from egg lecithins, as well as of the radioprotector alone shortly before (15-30 min) gamma irradiation of mice with 7.5 Gy (LD 100/30 ) provided high survival rate - accordingly 80% and 75%. Orally administered Adeturone incapsulated in tricomponent liposomes (dipalmitoil-DL-3-lecithin:cholesterine:stearilamine - 7:2:1) protected mice exposed to lethal X-irradiation (7.8 Gy, LD 90/30 ) for 0.5 to 4.5 hours. Adeturone, applied alone under these conditions 4.5 hours before irradiation, was ineffective. The results clearly demonstrated a prolonged radioprotective effect of Adeturone, administered per os as liposome suspension. 2 tabs., 17 refs

  1. Liposome imaging agents in personalized medicine

    DEFF Research Database (Denmark)

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

    2012-01-01

    In recent years the importance of molecular and diagnostic imaging has increased dramatically in the treatment planning of many diseases and in particular in cancer therapy. Within nanomedicine there are particularly interesting possibilities for combining imaging and therapy. Engineered liposomes...... that selectively localize in tumor tissue can transport both drugs and imaging agents, which allows for a theranostic approach with great potential in personalized medicine. Radiolabeling of liposomes have for many years been used in preclinical studies for evaluating liposome in vivo performance and has been...... start to consider how to use imaging for patient selection and treatment monitoring in connection to nanocarrier based medicines. Nanocarrier imaging agents could furthermore have interesting properties for disease diagnostics and staging. Here, we review the major advances in the development...

  2. Artificial Lipid Membranes: Past, Present, and Future.

    Science.gov (United States)

    Siontorou, Christina G; Nikoleli, Georgia-Paraskevi; Nikolelis, Dimitrios P; Karapetis, Stefanos K

    2017-07-26

    The multifaceted role of biological membranes prompted early the development of artificial lipid-based models with a primary view of reconstituting the natural functions in vitro so as to study and exploit chemoreception for sensor engineering. Over the years, a fair amount of knowledge on the artificial lipid membranes, as both, suspended or supported lipid films and liposomes, has been disseminated and has helped to diversify and expand initial scopes. Artificial lipid membranes can be constructed by several methods, stabilized by various means, functionalized in a variety of ways, experimented upon intensively, and broadly utilized in sensor development, drug testing, drug discovery or as molecular tools and research probes for elucidating the mechanics and the mechanisms of biological membranes. This paper reviews the state-of-the-art, discusses the diversity of applications, and presents future perspectives. The newly-introduced field of artificial cells further broadens the applicability of artificial membranes in studying the evolution of life.

  3. Applications of lipid nanocarriers for solid tumors therapy: literature review; Aplicacoes das nanoparticulas lipidicas no tratamento de tumores solidos: revisao de literatura

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Lidiane Correia de; Souza, Leonardo Gomes; Marreto, Ricardo Neves; Lima, Eliana Martins; Taveira, Stephania Fleury [Universidade Federal de Goias (UFG), Goiania, GO (Brazil). Fac. de Farmacia; Taveira, Eliseu Jose Fleury, E-mail: stephaniafleury@gmail.com [Hospital Erasto Gaertner, Curitiba, PR (Brazil). Oncologia Clinica

    2012-07-01

    Introduction: Lipid nanocarriers are systems used to target drugs to its site of action and have attracted attention of the scientific community because they are biocompatible and biodegradable. These systems can target drugs to solid tumors, providing sustained drug release in the site of action, thus increasing the utility of the antineoplastic chemotherapy. Objective: To review the available literature on in vivo experiments with lipid nanocarriers containing cytotoxic drugs for solid tumors treatment. Method: A search study was carried out in Pubmed{sup R} database from 2007 to 2011, with subject descriptors: liposomes, lipid nanoparticles, cancer and in vivo, with the boolean operator 'and' among them, in English. Results: 1,595 papers related to the use of liposomes and 77 related to lipid nanoparticles were found. Few studies reported in vivo experiments with lipid nanoparticles (28 papers) compared to liposomes (472 papers), since liposomes were developed two decades before lipid nanoparticles. Four liposomal medicines have already been approved and are used in the clinic while only one medicine containing lipid nanoparticles is in phase I of clinical studies. Conclusion: The number of papers related to the use of nanotechnology for cancer treatment is increasing rapidly, making important to know the different kinds of nanocarriers and, especially, those which are already used in the clinic. There are only few clinical studies on lipid nanocarriers; however, these systems present an enormous potential to improve the clinical practice in oncology. (author)

  4. Generation of fatty acids from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cardiolipin liposomes that stabilize recombinant human serum albumin.

    Science.gov (United States)

    Frahm, Grant E; Cameron, Brooke E; Smith, Jeffrey C; Johnston, Michael J W

    2013-06-01

    At elevated temperatures, studies have shown that serum albumin undergoes irreversible changes to its secondary structure. Anionic fatty acids and/or anionic surfactants have been shown to stabilize human serum albumin (HSA) against thermal denaturation through bridging hydrophobic domains and cationic amino acids residues of the protein. As albumin can readily interact with a variety of liposomes, this study proposes that cardiolipin delivered via 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes can improve the thermal stability of recombinant HSA produced in Saccharomyces cerevisiae (ScrHSA) in a similar manner to anionic fatty acids. Thermal stability and structure of ScrHSA in the absence and presence of DPPC/cardiolipin liposomes was assessed with U/V circular dichroism spectropolarimetry and protein thermal stability was confirmed with differential scanning calorimetry. Although freshly prepared DPPC/cardiolipin liposomes did not improve the stability of ScrHSA, DPPC/cardiolipin liposomes incubated at room temperature for 7 d (7dRT) dramatically improved the thermal stability of the protein. Mass spectrometry analysis identified the presence of fatty acids in the 7dRT liposomes, not identified in freshly prepared liposomes, to which the improved stability was attributed. The generation of fatty acids is attributed to either the chemical hydrolysis or oxidative cleavage of the unsaturated acyl chains of cardiolipin. By modulating the lipid composition through the introduction of lipids with higher acyl chain unsaturation, it may be possible to generate the stabilizing fatty acids in a more rapid manner.

  5. Stratum corneum hydration and skin surface pH in patients with atopic dermatitis.

    Science.gov (United States)

    Knor, Tanja; Meholjić-Fetahović, Ajša; Mehmedagić, Aida

    2011-01-01

    Atopic dermatitis (AD) is a chronically relapsing skin disease with genetic predisposition, which occurs most frequently in preschool children. It is considered that dryness and pruritus, which are always present in AD, are in correlation with degradation of the skin barrier function. Measurement of hydration and pH value of the stratum corneum is one of the noninvasive methods for evaluation of skin barrier function. The aim of the study was to assess skin barrier function by measuring stratum corneum hydration and skin surface pH of the skin with lesions, perilesional skin and uninvolved skin in AD patients, and skin in a healthy control group. Forty-two patients were included in the study: 21 young and adult AD patients and 21 age-matched healthy controls. Capacitance, which is correlated with hydration of stratum corneum and skin surface pH were measured on the forearm in the above areas by SM810/CM820/pH900 combined units (Courage AND Khazaka, Germany). The mean value of water capacitance measured in AD patients was 44.1 ± 11.6 AU (arbitrary units) on the lesions, 60.2 ± 12.4 AU on perilesional skin and 67.2 ± 8.8 AU on uninvolved skin. In healthy controls, the mean value was 74.1 ± 9.2 AU. The mean pH value measured in AD patients was 6.13 ± 0.52 on the lesions, 5.80 ± 0.41 on perilesional skin, and 5.54 ± 0.49 on uninvolved skin. In control group, the mean pH of the skin surface was 5.24 ± 0.40. The values of both parameters measured on lesional skin were significantly different (capacitance decreased and pH increased) from the values recorded on perilesional skin and uninvolved skin. The same held for the relation between perilesional and uninvolved skin. According to study results, the uninvolved skin of AD patients had significantly worse values of the measured parameters as compared with control group. The results of this study suggested the skin barrier function to be degraded in AD patients, which is specifically expressed in lesional skin.

  6. Structure-activity relationship of carbamate-linked cationic lipids bearing hydroxyethyl headgroup for gene delivery.

    Science.gov (United States)

    Zhi, Defu; Zhang, Shubiao; Qureshi, Farooq; Zhao, Yinan; Cui, Shaohui; Wang, Bing; Chen, Huiying; Yang, Baoling; Zhao, Defeng

    2013-12-01

    A novel series of carbamate-linked cationic lipids containing hydroxyl headgroup were synthesized and included in formulations for transfection assays. The DNA-lipid complexes were characterized for their ability to bind DNA, their size, ζ-potential and cytotoxicity. Compared with our previously reported cationic transfection lipid DDCDMA lacking the hydroxyl group and the commercially available, these cationic liposomes exhibited relatively higher transfection efficiency. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Fluorescence Resonance Energy Transfer in Polydiacetylene Liposomes

    Science.gov (United States)

    Li, Xuelian; Matthews, Shelton; Kohli, Punit

    2009-01-01

    Conjugated polydiacetylene (PDA) possessing stimuli-responsive properties has been intensively investigated for developing efficient sensors. We report here fluorescence resonance energy transfer (FRET) in liposomes synthesized using different molar ratios of dansyl-tagged diacetylene and diacetylene–carboxylic acid monomers. Photopolymerization of diacetylene resulted in cross-linked PDA liposomes. We used steady-state electronic absorption, emission, and fluorescence anisotropy (FA) analysis to characterize the thermal-induced FRET between dansyl fluorophores (donor) and PDA (acceptor). We found that the monomer ratio of acceptor to donor (Rad) and length of linkers (functional part that connects dansyl fluorophores to the diacetylene group in the monomer) strongly affected FRET. For Rad = 10 000, the acceptor emission intensity was amplified by more than 18 times when the liposome solution was heated from 298 to 338 K. A decrease in Rad resulted in diminished acceptor emission amplification. This was primarily attributed to lower FRET efficiency between donors and acceptors and a higher background signal. We also found that the FRET amplification of PDA emissions after heating the solution was much higher when dansyl was linked to diacetylene through longer and flexible linkers than through shorter linkers. We attributed this to insertion of dansyl in the bilayer of the liposomes, which led to an increased dansyl quantum yield and a higher interaction of multiple acceptors with limited available donors. This was not the case for shorter and more rigid linkers where PDA amplification was much smaller. The present studies aim at enhancing our understanding of FRET between fluorophores and PDA-based conjugated liposomes. Furthermore, receptor tagged onto PDA liposomes can interact with ligands present on proteins, enzymes, and cells, which will produce emission sensing signal. Therefore, using the present approach, there exist opportunities for designing FRET

  8. Stratum corneum profiles of inflammatory mediators in patch test reactions to common contact allergens and sodium lauryl sulfate

    NARCIS (Netherlands)

    Koppes, S. A.; Ljubojevic Hadzavdic, S.; Jakasa, I.; Franceschi, N.; Jurakić Tončić, R.; Marinović, B.; Brans, R.; Gibbs, S.; Frings-Dresen, M. H. W.; Rustemeyer, T.; Kezic, S.

    2017-01-01

    Background Recent studies have demonstrated allergen-specific differences in the gene expression of inflammatory mediators in patch tested skin. Objectives To determine levels of various inflammatory mediators in the stratum corneum (SC) after patch testing with common contact allergens and the skin

  9. Bed structure (frond bleaching, density and biomass) of the red alga Gelidium corneum under different irradiance levels

    Science.gov (United States)

    Quintano, E.; Díez, I.; Muguerza, N.; Figueroa, F. L.; Gorostiaga, J. M.

    2017-12-01

    In recent decades a decline in the foundation species Gelidium corneum (Hudson) J. V. Lamouroux has been detected along the Basque coast (northern Spain). This decline has been attributed to several factors, but recent studies have found a relationship between high irradiance and the biochemical and physiological stress of G. corneum. Since physiological responses to changes in light occur well before variations in morphology, the present study seeks to use a size-class demographic approach to investigate whether shallow subtidal populations of G. corneum off the Basque coast show different frond bleaching, density and biomass under different irradiance conditions. The results revealed that the bleaching incidence and cover were positively related to irradiance, whereas biomass was negatively related. The effect of the irradiance level on frond density was found to vary with size-class, i.e. fronds up to 15 cm showed greater densities under high light conditions (126.6 to 262.2 W m- 2) whereas the number of larger fronds (> 20 cm) per unit area was lower. In conclusion, the results of the present study suggest that irradiance might be a key factor for controlling along-shore bleaching, frond density and biomass in G. corneum. Further research should be carried out on the physiology of this canopy species in relation to its bed structure and on the interaction of irradiance and other abiotic (nutrients, temperature, wave energy) and biotic factors (grazing pressure).

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    Gu MJ

    2015-08-01

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

  12. Liposomal cancer therapy: exploiting tumor characteristics

    DEFF Research Database (Denmark)

    Kaasgaard, Thomas; Andresen, Thomas Lars

    2010-01-01

    an overview of current strategies for improving the different stages of liposomal cancer therapy, which involve transporting drug-loaded liposomes through the bloodstream, increasing tumor accumulation, and improving drug release and cancer cell uptake after accumulation at the tumor target site. What...... the reader will gain: The review focuses on strategies that exploit characteristic features of solid tumors, such as abnormal vasculature, overexpression of receptors and enzymes, as well as acidic and thiolytic characteristics of the tumor microenvironment. Take home message: It is concluded that the design...

  13. Evaluation of the interaction of surfactants with stratum corneum model membrane from Bothrops jararaca by DSC.

    Science.gov (United States)

    Baby, André Rolim; Lacerda, Aurea Cristina Lemos; Velasco, Maria Valéria Robles; Lopes, Patrícia Santos; Kawano, Yoshio; Kaneko, Telma Mary

    2006-07-06

    The interaction of surfactants sodium dodecyl sulfate (SDS), cetyl trimethyl ammonium chloride (CTAC) and lauryl alcohol ethoxylated (12 mol ethylene oxide) (LAE-12OE) was evaluated on the stratum corneum (SC) of shed snake skins from Bothrops jararaca, used as model membrane, and thermal characterized by differential scanning calorimetry (DSC). Surfactant solutions were employed above of the critical micellar concentration (CMC) with treatment time of 8h. The SDS interaction with the SC model membrane has increased the characteristic transition temperature of 130 degrees C in approximately 10 degrees C for the water loss and keratin denaturation, indicating an augmentation of the water content. Samples treated with CTAC have a decrease of the water loss temperature, while, for the LAE-12OE treated samples, changes on the transition temperature have not been observed.

  14. Exploring the Correlation Between Lipid Packaging in Lipoplexes and Their Transfection Efficacy

    Science.gov (United States)

    Moghaddam, Behfar; McNeil, Sarah E.; Zheng, Qinguo; Mohammed, Afzal R.; Perrie, Yvonne

    2011-01-01

    Whilst there is a large body of evidence looking at the design of cationic liposomes as transfection agents, correlates of formulation to function remain elusive. In this research, we investigate if lipid packaging can give further insights into transfection efficacy. DNA lipoplexes composed of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) in combination with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or 1,2-stearoyl-3-trimethylammonium-propane (DSTAP) were prepared by the lipid hydration method. Each of the formulations was prepared by hydration in dH2O or phosphate buffer saline (PBS) to investigate the effect of buffer salts on lipoplex physicochemical characteristics and in vitro transfection. In addition, Langmuir monolayer studies were performed to investigate any possible correlation between lipid packaging and liposome attributes. Using PBS, rather than dH2O, to prepare the lipoplexes increased the size of vesicles in most of formulations and resulted in variation in transfection efficacies. However, one combination of lipids (DSPE:DOTAP) could not form liposomes in PBS, whilst the DSPE:DSTAP combination could not form liposomes in either aqueous media. Monolayer studies demonstrated saturated lipid combinations offered dramatically closer molecular packing compared to the other combinations which could suggest why this lipid combination could not form vesicles. Of the lipoplexes prepared, those formulated with DSTAP showed higher transfection efficacy, however, the effect of buffer on transfection efficiency was formulation dependent. PMID:24309311

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

    Science.gov (United States)

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

    2009-07-20

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

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Mukthavaram R

    2013-10-01

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

  18. Dew point effect of cooled hydrogel pads on human stratum corneum biosurface.

    Science.gov (United States)

    Xhauflaire-Uhoda, Emmanuelle; Paquet, Philippe; Piérard, Gérald E

    2008-01-01

    Cooled hydrogel pads are used to prevent overheating effects of laser therapy. They do not induce cold injuries to the skin, but their more subtle physiological effects have not been thoroughly studied. To describe the changes in transepidermal water loss and electrometric properties of the skin surface following application of cooled hydrogel pads. Measurements were performed on normal forearm skin of 27 healthy volunteers and on freshly excised skin from abdominoplasty. LaserAid hydrogel pads cooled to 4 degrees C were placed for 15 min on the forearm skin. Measurements of transepidermal water loss (TEWL) and electrometric properties (Corneometer, Nova DPM 900) were performed before application and after removal of the cooled pads. A consistent increase in corneometer units, dermal phase meter (DPM) values and TEWL were recorded at removal of the cooled hydrogel pads. Both the in vivo and in vitro assessments brought similar information. The similar changes disclosed in vitro and in vivo suggest that a common physical process is operating in these conditions. The observed phenomenon is opposite to the predicted events given by the Arrhenius law probably because of the combination of cooling and occlusion by the pads. A dew point effect (air temperature at which relative humidity is maximal) is likely involved in the moisture content of the stratum corneum. Thus, the biological impact of using cooling hydrogel pads during laser therapy is different from the effect of a cryogenic spray cooling procedure. The better preservation of the water balance in the stratum corneum by the cooled hydrogel pads could have a beneficial esthetic effect on laser treated areas. (c) 2008 S. Karger AG, Basel.

  19. From observational to analytical morphology of the stratum corneum: progress avoiding hazardous animal and human testings

    Directory of Open Access Journals (Sweden)

    Piérard GE

    2015-03-01

    Full Text Available Gérald E Piérard,1,2 Justine Courtois,1 Caroline Ritacco,1 Philippe Humbert,2,3 Ferial Fanian,3 Claudine Piérard-Franchimont1,4,5 1Laboratory of Skin Bioengineering and Imaging (LABIC, Department of Clinical Sciences, Liège University, Liège, Belgium; 2University of Franche-Comté, Besançon, France; 3Department of Dermatology, University Hospital Saint-Jacques, Besançon, France; 4Department of Dermatopathology, Unilab Lg, University Hospital of Liège, Liège, Belgium; 5Department of Dermatology, Regional Hospital of Huy, Huy, Belgium Background: In cosmetic science, noninvasive sampling of the upper part of the stratum corneum is conveniently performed using strippings with adhesive-coated discs (SACD and cyanoacrylate skin surface strippings (CSSSs. Methods: Under controlled conditions, it is possible to scrutinize SACD and CSSS with objectivity using appropriate methods of analytical morphology. These procedures apply to a series of clinical conditions including xerosis grading, comedometry, corneodynamics, corneomelametry, corneosurfametry, corneoxenometry, and dandruff assessment. Results: With any of the analytical evaluations, SACD and CSSS provide specific salient information that is useful in the field of cosmetology. In particular, both methods appear valuable and complementary in assessing the human skin compatibility of personal skincare products. Conclusion: A set of quantitative analytical methods applicable to the minimally invasive and low-cost SACD and CSSS procedures allow for a sound assessment of cosmetic effects on the stratum corneum. Under regular conditions, both methods are painless and do not induce adverse events. Globally, CSSS appears more precise and informative than the regular SACD stripping. Keywords: irritation, morphometry, quantitative morphology, stripping

  20. 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

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

    OpenAIRE

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    M. A. Kisjakova

    2010-07-01

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

  3. Liposomal solubilization of new 3-hydroxy-quinolinone derivatives with promising anticancer activity: a screening method to identify maximum incorporation capacity

    DEFF Research Database (Denmark)

    Di Cagno, Massimiliano; Styskala, Jakub; Hlaváč, Jan

    2011-01-01

    Four new 3-hydroxy-quinolinone derivatives with promising anticancer activity could be solubilized using liposomes as vehicle to an extent that allows their in vitro and in vivo testing without use of toxic solvent(s). A screening method to identify the maximum incorporation capacity of hydrophobic......, resulting in a 200-500-fold increase in apparent solubility. Drug-to-lipid ratios in the range of 2-5 µg/mg were obtained. Interestingly, the four quinolinone derivatives have shown different association tendencies with liposomes, probably due to the physicochemical properties of the different group bonded...

  4. Solar radiation (PAR and UVA) and water temperature in relation to biochemical performance of Gelidium corneum (Gelidiales, Rhodophyta) in subtidal bottoms off the Basque coast

    Science.gov (United States)

    Quintano, Endika; Ganzedo, Unai; Díez, Isabel; Figueroa, Félix L.; Gorostiaga, José M.

    2013-10-01

    Gelidium corneum (Hudson) J.V. Lamouroux is a very important primary producer in the Cantabrian coastal ecosystem. Some local declines in their populations have been recently detected in the Basque coast. Occurrences of yellowing and an unusual branch breakdown pattern have also been reported for some G. corneum populations. In order to gain further insight into those environmental stressors operating at a local scale, here we investigate if shallow subtidal populations of G. corneum living under potentially different conditions of irradiance (PAR and UVA) and water temperature exhibit differences in some biochemical indicators of stress, namely C:N, antioxidant activity (radical cation of 2,2‧-azino-bis (3-ethylbenzothiazoline-6-sulfonate); ABTS+ assay) and mycosporine-like amino acids (MAAs) (Asterine 330 and Palythine). We hypothesised that G. corneum subjected to higher ambient levels of irradiance and water temperature would show higher C:N ratios, lower antioxidant activity and higher MAA concentrations. Our results partially support this hypothesis. We found that G. corneum exposed to increased levels of irradiance (PAR, UVA) exhibited greater C:N ratios and lower antioxidant activity (higher IC50), whereas no relationship was found regarding MAAs. No differences in biochemical performance in relation to temperature were detected among G. corneum exposed to comparable high light. Similarly, G. corneum growing under lower UVA radiation levels showed no differences in any of the measured biochemical variables with regard to PAR and water temperature. These findings suggest that, among the environmental factors examined, UVA radiation may be an important driver in regulating the along-shore variation in G. corneum biochemical performance. Therefore, the role of irradiance, especially UV radiation, in potential future alterations in Cantabrian G. corneum populations cannot be ruled out as a potential underlying factor.

  5. The radiation effects on lipid bilayers

    International Nuclear Information System (INIS)

    Ikigai, Hajime; Matsuura, Tomio; Narita, Noboru; Ozawa, Atsushi.

    1980-01-01

    The Radiation effects on lipid bilayers are studied by the electron spin resonance. Egg lecithin liposomes and human erythrocytes are labeled with spin probes (5 SAL, 12 SAL). Effects of membrane fluidity by X-Ray (or ultraviolet) irradiation are measured by change of the order parameter S. The results obtained are as follows: 1) A similar tendency is observed on the order parameter S between X-Ray irradiated egg lecithin liposomes and human erythrocytes. 2) The rapid changes of the membrane fluidity are observed below 1 krad. The fluctuation of membrane fluidity decreases above 1 krad, consequently the membrane has a tendency changing to a rigid state at low dose area. 3) It is suggested that the more effective radicals are hydroxyl radicals and superoxide radicals. 4) The effects of ultraviolet irradiation with hydrogen peroxide show that hydroxyl radicals lead to changes of membrane fluidity. (author)

  6. 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.

  7. Antimalarial Activity of Orally Administered Curcumin Incorporated in Eudragit®-Containing Liposomes

    Directory of Open Access Journals (Sweden)

    Elisabet Martí Coma-Cros

    2018-05-01

    Full Text Available Curcumin is an antimalarial compound easy to obtain and inexpensive, having shown little toxicity across a diverse population. However, the clinical use of this interesting polyphenol has been hampered by its poor oral absorption, extremely low aqueous solubility and rapid metabolism. In this study, we have used the anionic copolymer Eudragit® S100 to assemble liposomes incorporating curcumin and containing either hyaluronan (Eudragit-hyaluronan liposomes or the water-soluble dextrin Nutriose® FM06 (Eudragit-nutriosomes. Upon oral administration of the rehydrated freeze-dried nanosystems administered at 25/75 mg curcumin·kg−1·day−1, only Eudragit-nutriosomes improved the in vivo antimalarial activity of curcumin in a dose-dependent manner, by enhancing the survival of all Plasmodium yoelii-infected mice up to 11/11 days, as compared to 6/7 days upon administration of an equal dose of the free compound. On the other hand, animals treated with curcumin incorporated in Eudragit-hyaluronan liposomes did not live longer than the controls, a result consistent with the lower stability of this formulation after reconstitution. Polymer-lipid nanovesicles hold promise for their development into systems for the oral delivery of curcumin-based antimalarial therapies.

  8. Amino Terminal Region of Dengue Virus NS4A Cytosolic Domain Binds to Highly Curved Liposomes

    Directory of Open Access Journals (Sweden)

    Yu-Fu Hung

    2015-07-01

    Full Text Available Dengue virus (DENV is an important human pathogen causing millions of disease cases and thousands of deaths worldwide. Non-structural protein 4A (NS4A is a vital component of the viral replication complex (RC and plays a major role in the formation of host cell membrane-derived structures that provide a scaffold for replication. The N-terminal cytoplasmic region of NS4A(1–48 is known to preferentially interact with highly curved membranes. Here, we provide experimental evidence for the stable binding of NS4A(1–48 to small liposomes using a liposome floatation assay and identify the lipid binding sequence by NMR spectroscopy. Mutations L6E;M10E were previously shown to inhibit DENV replication and to interfere with the binding of NS4A(1–48 to small liposomes. Our results provide new details on the interaction of the N-terminal region of NS4A with membranes and will prompt studies of the functional relevance of the curvature sensitive membrane anchor at the N-terminus of NS4A.

  9. 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.

  10. 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.

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Bharathi Raja Rajaganapathy

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

  13. Development of coated liposomes loaded with ghrelin for nose-to-brain delivery for the treatment of cachexia

    Directory of Open Access Journals (Sweden)

    Salade L

    2017-11-01

    Full Text Available Laurent Salade,1 Nathalie Wauthoz,1 Magali Deleu,2 Marjorie Vermeersch,3 Carine De Vriese,1 Karim Amighi,1 Jonathan Goole1 1Laboratoire de Pharmacie Galénique et de Biopharmacie, Université libre de Bruxelles (ULB, Brussels, 2Laboratoire de Biophysique Moléculaire aux Interfaces, Gembloux Agro-Bio Tech, Université de Liège, Gembloux, 3Centre for Microscopy and Molecular Imaging (CMMI, Charleroi, Belgium Abstract: The aim of the present study was to develop a ghrelin-containing formulation based on liposomes coated with chitosan intended for nose–brain delivery for the treatment of cachexia. Among the three types of liposomes developed, anionic liposomes provided the best results in terms of encapsulation efficiency (56% and enzymatic protection against trypsin (20.6% vs 0% for ghrelin alone and carboxylesterase (81.6% vs 17.2% for ghrelin alone. Ghrelin presented both electrostatic and hydrophobic interactions with the anionic lipid bilayer, as demonstrated by isothermal titration calorimetry. Then, anionic liposomes were coated with N-(2-hydroxypropyl-3-trimethyl ammonium chitosan chloride. The coating involved a size increment from 146.9±2.7 to 194±6.1 nm, for uncoated and coated liposomes, respectively. The ζ-potential was similarly increased from -0.3±1.2 mV to 6±0.4 mV before and after coating, respectively. Chitosan provided mucoadhesion, with an increase in mucin adsorption of 22.9%. Enhancement of permeation through the Calu3 epithelial monolayer was also observed with 10.8% of ghrelin recovered in the basal compartment in comparison to 0% for ghrelin alone. Finally, aerosols generated from two nasal devices (VP3 and SP270 intended for aqueous dispersion were characterized with either coated or uncoated liposomes. Contrarily to the SP270 device, VP3 device showed minor changes between coated and uncoated liposome aerosols, as shown by their median volume diameters of 38.4±5.76 and 37.6±5.74 µm, respectively. Overall, the

  14. 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

  15. 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.

  16. Design, optimization and characterization of coenzyme Q10- and D-panthenyl triacetate-loaded liposomes

    Directory of Open Access Journals (Sweden)

    Çelik B

    2017-07-01

    Full Text Available Burak Çelik,1 Ali Asram Sağıroğlu,1 Samet Özdemir2 1Department of Pharmaceutical Technology, Faculty of Pharmacy, Bezmialem Vakif University, 2Department of Pharmaceutical Technology, Faculty of Pharmacy, Yeditepe University, Istanbul, Turkey Abstract: Coenzyme Q10 (CoQ10 is a lipid-soluble molecule found naturally in many eukaryotic cells and is essential for electron transport chain and energy generation in mitochondria. D-Panthenyl triacetate (PTA is an oil-soluble derivative of D-panthenol, which is essential for coenzyme A synthesis in the epithelium. Liposomal formulations that encapsulate both ingredients were prepared and optimized by applying response surface methodology for increased stability and skin penetration. The optimum formulation comprised 4.17 mg CoQ10, 4.22 mg PTA and 13.95 mg cholesterol per 100 mg of soy phosphatidylcholine. The encapsulation efficiency of the optimized formulation for CoQ10 and PTA was found to be 90.89%±3.61% and 87.84%±4.61%, respectively. Narrow size distribution was achieved with an average size of 161.6±3.6 nm, while a spherical and uniform shape was confirmed via scanning electron microscopy and transmission electron microscopy images. Cumulative release of 90.93% for PTA and 24.41% for CoQ10 was achieved after 24 hours of in vitro release study in sink conditions. Physical stability tests indicated that the optimized liposomes were suitable for storage at 4°C for at least 60 days. The results suggest that the optimized liposomal formulation would be a promising delivery system for both ingredients in various topical applications. Keywords: coenzyme Q10, D-panthenyl triacetate, liposomes, response surface methodology, stability

  17. Zinc in the prevention of Fe2initiated lipid and protein oxidation

    Directory of Open Access Journals (Sweden)

    M. PAOLA ZAGO

    2000-01-01

    Full Text Available In the present study we characterized the capacity of zinc to protect lipids and proteins from Fe2+-initiated oxidative damage. The effects of zinc on lipid oxidation were investigated in liposomes composed of brain phosphatidylcholine (PC and phosphatidylserine (PS at a molar relationship of 60:40 (PC:PS, 60:40. Lipid oxidation was evaluated as the oxidation of cis-parinaric acid or as the formation of 2-thiobarbituric acid-reactive substances (TBARS. Zinc protected liposomes from Fe2+ (2.5-50 muM-supported lipid oxidation. However, zinc (50 muM did not prevent the oxidative inactivation of glutamine synthelase and glucose 6-phosphate dehydrogenase when rat brain superntants were oxidized in the presence of 5 muM Fe2+ and 0.5 mM H2O2 .We also studied the interactions of zinc with epicatechin in the prevention of liid oxidation in liposomes. The simulaneous addition of 0.5 muM epicatechin (EC and 50 muM zinc or EC separately. Zinc (50 muM also protecte liposomes from the stimulatory effect of aluminum on Fe2+-initiated lipid oxidation. Zinc could play an important role as an antioxidant in biological systems, replacing iron and other metals with pro-oxidant activity from binding sites and interacting with other components of the oxidant defense system.

  18. Enhanced antidepressant-like effects of the macromolecule trefoil factor 3 by loading into negatively charged liposomes

    Directory of Open Access Journals (Sweden)

    Qin J

    2014-11-01

    Full Text Available Jing Qin,1 Xu Yang,1–3 Jia Mi,4 Jianxin Wang,1 Jia Hou,1,2 Teng Shen,1 Yongji Li,2 Bin Wang,4 Xuri Li,4 Weili Zhu5 1Department of Pharmaceutics, School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, 2Department of Pharmaceutics, School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 3Department of Pharmacy, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, 4Binzhou Medical University, Yantai, 5National Institute on Drug Dependence, Peking University, Beijing, People’s Republic of China Abstract: Immunocytes, mainly neutrophils and monocytes, exhibit an intrinsic homing property, enabling them to migrate to sites of injury and inflammation. They can thus act as Trojan horses carrying concealed drug cargoes while migrating across impermeable barriers to sites of disease, especially the blood–brain barrier (BBB. In this study, to target circulating phagocytic cells, we formulated negatively charged nanosize liposomes and loaded trefoil factor 3 (TFF3 into liposomes by the pH-gradient method. According to the optimized formulation (5:1.5 of lipid to cholesterol, 10:1 of lipid to drug, 10 mg/mL of lipid concentration, and 10 mmol/L of phosphate-buffered saline, 44.47% entrapment efficiency was obtained for TFF3 liposomes with 129.6 nm particle size and –36.6 mV zeta potential. Compared with neutrally charged liposomes, the negatively charged liposomes showed a strong binding capacity with monocytes and were effectively carried by monocytes to cross the BBB in vitro. Furthermore, enhanced antidepressant-like effects were found in the tail-suspension and forced-swim tests in mice, as measured by decreased immobility time, as well as increased swimming time and reduced immobility in rats. These results suggested that negatively charged liposomes could improve the behavioral responses of TFF3, and our study opens up a new way for the development of

  19. Adiabatic differential scanning calorimetric study of divalent cation induced DNA - DPPC liposome formulation compacted for gene delivery

    Directory of Open Access Journals (Sweden)

    Erhan Süleymanoglu

    2004-11-01

    Full Text Available Complexes between nucleic acids and phospholipid vesicles have been developed as stable non-viral gene delivery vehicles. Currently employed approach uses positively charged lipid species and a helper zwitterionic lipid, the latter being applied for the stabilization of the whole complex. However, besides problematic steps during their preparation, cationic lipids are toxic for cells. The present work describes some energetic issues pertinent to preparation and use of neutral lipid-DNA self-assemblies, thus avoiding toxicity of lipoplexes. Differential scanning calorimetry data showed stabilization of polynucleotide helix upon its interaction with liposomes in the presence of divalent metal cations. It is thus possible to suggest this self-assembly as an improved formulation for use in gene delivery.

  20. The effect of MLS laser radiation on cell lipid membrane.

    Science.gov (United States)

    Pasternak, Kamila; Wróbel, Dominika; Nowacka, Olga; Pieszyński, Ireneusz; Bryszewska, Maria; Kujawa, Jolanta

    2018-03-14

    Authors of numerous publications have proved the therapeutic effect of laser irradiation on biological material, but the mechanisms at cellular and subcellular level are not yet well understood. The aim of this study was to assess the effect of laser radiation emitted by the MLS M1 system (Multiwave Locked System) at two wavelengths (808 nm continuous and 905 nm pulsed) on the stability and fluidity of liposomes with a lipid composition similar to that of human erythrocyte membrane or made of phosphatidylocholine. Liposomes were exposed to low-energy laser radiation at surface densities 195 mW/cm2 (frequency 1,000 Hz) and 230 mW/cm2 (frequency 2,000 Hz). Different doses of radiation energy in the range 0-15 J were applied. The surface energy density was within the range 0.46 - 4.9 J/cm 2. The fluidity and stability of liposomes subjected to such irradiation changed depending on the parameters of radiation used. Since MLS M1 laser radiation, depending on the parameters used, affects fluidity and stability of liposomes with the lipid content similar to erythrocyte membrane, it may also cause structural and functional changes in cell membranes.

  1. 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.

  2. 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

  3. 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...

  4. 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 (< 4% content variation) incorporated into the SBG hydrogel. Addition of PG decreased the necessary 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.

  5. Penetration route of functional molecules in stratum corneum studied by time-resolved small- and wide-angle x-ray diffraction

    International Nuclear Information System (INIS)

    Hatta, Ichiro; Ohta, Noboru; Yagi, Naoto; Nakazawa, Hiromitsu; Obata, Yasuko; Inoue, Katsuaki

    2011-01-01

    We studied effects of functional molecules on corneocytes in stratum corneum using time-resolved small- and wide-angle x-ray diffraction after applying a functional molecule. From these results it was revealed that in the stratum corneum a typical hydrophilic molecule, ethanol, penetrates via the transcellular route and on the other hand a typical hydrophobic molecule, d-limonene, penetrates via the intercellular route.

  6. Antioxidant properties of biohybrids based on liposomes and sage silver nanoparticles.

    Science.gov (United States)

    Barbinta-Patrascu, Marcela Elisabeta; Bunghez, Ioana-Raluca; Iordache, Stefan Marian; Badea, Nicoleta; Fierascu, Radu-Claudiu; Ion, Rodica Mariana

    2013-03-01

    This paper is aimed to describe a simple and rapid eco-friendly bottom-up approach for the preparation of antioxidant silver bionanostructures using a leaf extract from sage (Salvia officinalis L.). The bioreduction property of sage in the synthesis of silver nanoparticles was investigated by UV-VIS and Attenuated Total Reflectance Fourier Transform Infrared spectroscopy. During their preparation, the particle size analysis was performed by using Dynamic Light Scattering technique. Ultrasonic irradiation was used to obtain sage silver nanoparticles. The morphology (size and shape) of the herbal silver nanoparticles was evaluated by Scanning Electron Microscopy that revealed the formation of spherical phytonanoparticles with size less than 80 nm. In order to increase their stability and their biocompatibility, the sage silver nanoparticles were introduced in two types of liposomes: soybean lecithin- and Chla-DPPC-lipid vesicles which were prepared by thin film hydration method. X-Ray Fluorescence analysis confirmed the silver presence in liposomes/sage-AgNPs biohybrids. The stability of liposomes/herbal AgNPs bioconstructs was checked by zeta potential measurements. The most stable biohybrids: Chla-DPPC/sage-AgNPs with zeta potential value of -34.2 mV, were characterized by Atomic Force Microscopy revealing the spherical and quasi-spherical shaped profiles of these nanobiohybrids with size less than 96 nm. The antioxidant activity of the silver bionanostructures was evaluated using chemiluminescence assay. The developed eco-friendly silver phytonanostructures based on lipid membranes, nanosilver and sage extract, manifest strong antioxidant properties (between 86.5% and 98.6%).

  7. 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.

  8. 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.

  9. FDA Approves Irinotecan Liposome to Treat Pancreatic Cancer

    Science.gov (United States)

    Patients with metastatic pancreatic cancer that has progressed after receiving gemcitabine-based chemotherapy now have a new treatment option: irinotecan liposome in combination with fluorouracil and leucovorin.

  10. [Development of a Novel Liposomal DDS by Manipulating Pharmacokinetics and Intracellular Trafficking for Drug Therapy and Nucleic Acid Medicine].

    Science.gov (United States)

    Hatakeyama, Hiroto

    2018-01-01

     Nucleic acid therapy is expected to be a next generation medicine. We recently developed a multifunctional envelope-type nano device (MEND) for use as a novel delivery system. The modification of polyethylene glycol (PEG), i.e., PEGylation, is useful for achieving the delivery of MENDs to tumors via an enhanced permeability and retention (EPR) effect. However, PEGylation strongly inhibits the cellular uptake and endosomal escape of MEND, which results in significant loss of action, and therefore lost effectiveness, of the cargo therapeutic. For successful nucleic acid delivery in cancer treatment, the crucial problem associated with the use of PEG, known as the "PEG dilemma", must be solved. In this review, we describe the development and application of MEND in overcoming the PEG dilemma based on manipulating both the pharmacokinetics and intracellular trafficking of cellular uptake and endosomal release using a cleavable PEG lipid, a pH-sensitive fusogenic peptide, and a pH-sensitive cationic lipid. We also developed dual-ligand liposomes with a controlled diameter of around 300 nm, then modified these with a specific ligand and a cell penetrating peptide designed to target the neovasculature of tumors. Dual-ligand liposomes could induce an anti-tumor effect in drug resistant tumors by delivering drugs to tumor blood vessels, rather than to the cancer cells themselves. Here, we review our recent efforts to develop a novel liposomal drug delivery system (DDS) by manipulating pharmacokinetics and intracellular trafficking for drug therapy and nucleic acid medicine.

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

    Directory of Open Access Journals (Sweden)

    Nivesh K. Mittal

    2018-04-01

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

  12. Adsorption and desorption behaviors of cationic liposome-DNA complexes upon lipofection in inside and outside biomembrane models using a dynamic quasi-elastic laser scattering method.

    Science.gov (United States)

    Uchiyama, Yoshiko; Yui, Hiroharu; Sawada, Tsuguo

    2004-11-01

    The dynamic behaviors of cationic liposome-DNA complexes in inside and outside biomembrane models upon lipofection were investigated using the time-resolved quasi-elastic laser scattering (QELS) method. Inside and outside biomembrane models with similar phospholipid compositions to those in living cells were formed at a tetradecane/phosphate buffered saline (TD/PBS) interface. Cationic liposome-DNA complexes were injected into the buffer subphase, and their adsorption/desorption behaviors at the biomembrane models were monitored through changes in the interfacial tension. We found that the adsorption rate of the complexes increased 2.6 times more in the outside model than in the inside one. The adsorption rate of DNA alone did not show a remarkable difference from one side to the other; however, the adsorption rate of the cationic liposome alone showed a similar tendency to that of the liposome-DNA complex. These results indicated that the difference in lipid composition induced a different dynamic behavior of exogenous biomolecules and that the cationic liposomes played an important role in the faster incorporation of DNA into cells upon lipofection.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-01-01

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

  14. Lipid somersaults

    DEFF Research Database (Denmark)

    Günther-Pomorski, Thomas; Menon, Anant K.

    2016-01-01

    Membrane lipids diffuse rapidly in the plane of the membrane but their ability to flip spontaneously across a membrane bilayer is hampered by a significant energy barrier. Thus spontaneous flip-flop of polar lipids across membranes is very slow, even though it must occur rapidly to support diverse...... aspects of cellular life. Here we discuss the mechanisms by which rapid flip-flop occurs, and what role lipid flipping plays in membrane homeostasis and cell growth. We focus on conceptual aspects, highlighting mechanistic insights from biochemical and in silico experiments, and the recent, ground......-breaking identification of a number of lipid scramblases....

  15. Review of Stratum Corneum Impedance Measurement in Non-Invasive Penetration Application

    Directory of Open Access Journals (Sweden)

    Fei Lu

    2018-03-01

    Full Text Available Due to advances in telemedicine, mobile medical care, wearable health monitoring, and electronic skin, great efforts have been directed to non-invasive monitoring and treatment of disease. These processes generally involve disease detection from interstitial fluid (ISF instead of blood, and transdermal drug delivery. However, the quantitative extraction of ISF and the level of drug absorption are greatly affected by the individual’s skin permeability, which is closely related to the properties of the stratum corneum (SC. Therefore, measurement of SC impedance has been proposed as an appropriate way for assessing individual skin differences. In order to figure out the current status and research direction of human SC impedance detection, investigations regarding skin impedance measurement have been reviewed in this paper. Future directions are concluded after a review of impedance models, electrodes, measurement methods and systems, and their applications in treatment. It is believed that a well-matched skin impedance model and measurement method will be established for clinical and point-of care applications in the near future.

  16. Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate.

    Science.gov (United States)

    De Jongh, Cindy M; Verberk, Maarten M; Withagen, Carien E T; Jacobs, John J L; Rustemeyer, Thomas; Kezic, Sanja

    2006-06-01

    Little is known about cytokines involved in chronic irritant contact dermatitis. Individual cytokine profiles might explain at least part of the differences in the individual response to irritation. Our objective was to investigate the relation between baseline stratum corneum (SC) cytokine levels and the skin response to a single and a repeated irritation test. This study also aimed to determine changes in SC cytokine levels after repeated irritation. Transepidermal water loss (TEWL) and erythema were measured in 20 volunteers after single 24-hr exposure to 1% sodium lauryl sulfate (SLS), and during and after repeated exposure to 0.1% SLS over a 3-week period. SC cytokine levels were measured from an unexposed skin site and from the repeatedly exposed site. Interleukin (IL)-1alpha decreased by 30% after repeated exposure, while IL-1RA increased 10-fold and IL-8 increased fourfold. Baseline IL-1RA and IL-8 values were predictors of TEWL and erythema after single exposure (r = 0.55-0.61). 6 subjects showed barrier recovery during repeated exposure. Baseline IL-1RA and IL-8 levels are likely to be indicators of higher skin irritability after single exposure to SLS. Barrier repair in some of the subjects might explain the lack of agreement between the TEWL response after single and repeated irritation.

  17. The Human Stratum Corneum Prevents Small Gold Nanoparticle Penetration and Their Potential Toxic Metabolic Consequences

    Directory of Open Access Journals (Sweden)

    David C. Liu

    2012-01-01

    Full Text Available Nanoparticles are being used in multiple applications, ranging from biomedical and skin care products (e.g., sunscreen through to industrial manufacturing processes (e.g., water purification. The increase in exposure has led to multiple reports on nanoparticle penetration and toxicity. However, the correlation between nanoparticle size and its penetration without physical/chemical enhancers through the skin is poorly understood—with studies instead focusing primarily on skin penetration under disrupted conditions. In this paper, we investigate the penetration and metabolic effects of 10 nm, 30 nm, and 60 nm gold nanoparticles within viable excised human skin after 24-hour exposure using multiphoton tomograph-fluorescence lifetime imaging microscopy. After 24 hour treatment with the 10, 30, and 60 nm gold nanoparticles, there was no significant penetration detected below the stratum corneum. Furthermore, there were no changes in metabolic output (total NAD(PH in the viable epidermis posttreatment correlating with lack of penetration of nanoparticles. These results are significant for estimating topical nanoparticle exposure in humans where other model systems may overestimate the exposure of nanoparticles to the viable epidermis. Our data shows that viable human skin resists permeation of small nanoparticles in a size range that has been reported to penetrate deeply in other skin models.

  18. Penetration of gold nanoparticles across the stratum corneum layer of thick-Skin.

    Science.gov (United States)

    Raju, Gayathri; Katiyar, Neeraj; Vadukumpully, Sajini; Shankarappa, Sahadev A

    2018-02-01

    Transdermal particulate penetration across thick-skin, such as that of palms and sole, is particularly important for drug delivery for disorders such as small fiber neuropathies. Nanoparticle-based drug delivery across skin is believed to have much translational applications, but their penetration especially through thick-skin, is not clear. This study specifically investigates the effectiveness of gold nanoparticles (AuNPs) for thick-skin penetration, especially across the stratum corneum (SC) as a function of particle size. The thick-skinned hind-paw of rat was used to characterize depth and distribution of AuNPs of varying sizes, namely, 22±3, 105±11, and 186±20nm. Epidermal penetration of AuNPs was characterized both, in harvested skin from the hind-paw using a diffusion chamber, as well as in vivo. Harvested skin segments exposed to 22nm AuNPs for only 3h demonstrated higher penetration (pthick-skin allows nanoparticle penetration and acts as a depot for release of AuNPs into circulation long after the initial exposure has ceased. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  19. Relative uptake of minoxidil into appendages and stratum corneum and permeation through human skin in vitro.

    Science.gov (United States)

    Grice, Jeffrey E; Ciotti, Susan; Weiner, Norman; Lockwood, Peter; Cross, Sheree E; Roberts, Michael S

    2010-02-01

    We examined uptake of the model therapeutic agent, minoxidil, into appendages, stratum corneum (SC), and through human skin, under the influence of different vehicles. Quantitative estimation of therapeutic drug deposition into all three areas has not previously been reported. Finite doses of minoxidil (2%, w/v) in formulations containing varying amounts of ethanol, propylene glycol (PG), and water (60:20:20, 80:20:0, and 0:80:20 by volume, respectively) were used. Minoxidil in SC (by tape stripping), appendages (by cyanoacrylate casting), and receptor fluid was determined by liquid scintillation counting. At early times (30 min, 2 h), ethanol-containing formulations (60:20:20 and 80:20:0) caused significantly greater minoxidil retention in SC and appendages, compared to the formulation lacking ethanol (0:80:20). A significant increase in minoxidil receptor penetration occurred with the PG-rich 0:80:20 formulation after 12 h. We showed that deposition of minoxidil into appendages, SC, and skin penetration into receptor fluid were similar in magnitude. Transport by the appendageal route is likely to be a key determinant of hair growth promotion by minoxidil. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association.

  20. Ethnic differences in stratum corneum functions between Chinese and Thai infants residing in Bangkok, Thailand.

    Science.gov (United States)

    Fujimura, Tsutomu; Miyauchi, Yuki; Shima, Kyoko; Hotta, Mitsuyuki; Tsujimura, Hisashi; Kitahara, Takashi; Takema, Yoshinori; Palungwachira, Pakhawadee; Laohathai, Diane; Chanthothai, Jetchawa; Nararatwanchai, Thamthiwat

    2018-01-01

    Ethnic and racial differences in infant skin have not been well characterized. The purpose of this study was to establish whether there are ethnic differences and similarities in the stratum corneum (SC) functions of Thai and Chinese infants. Healthy infants 6 to 24 months of age (N = 60; 30 Thai, 30 Chinese) who resided in Bangkok, Thailand, were enrolled. Transepidermal water loss (TEWL) and SC hydration (capacitance) on the thigh, buttock, and upper arm were measured. Ceramide content was determined in the SC on the upper arm. SC hydration was not remarkably different between the two ethnicities at any site measured, but TEWL was significantly higher in Chinese infants than in Thai infants at all sites. Hydration of the SC was not significantly correlated with age in either ethnicity. TEWL had significant but weak correlations with age on the thigh and upper arm in Thai infants. Ceramide content was significantly higher in Chinese SC than in Thai SC. No relationship between ceramide content and TEWL or hydration was observed in either ethnicity. The significant differences in TEWL and ceramide contents between Chinese and Thai infant skin could prove useful in designing skin care and diapering products that are best suited for each ethnicity. © 2017 Wiley Periodicals, Inc.

  1. In vivo studies of aquaporins 3 and 10 in human stratum corneum

    DEFF Research Database (Denmark)

    Jungersted, Jakob Mutanu; Bomholt, Julie; Bajraktari, Niada

    2013-01-01

    migration and proliferation with consequences for the antimicrobial defense of the skin. AQP3 and AQP10 are aqua-glyceroporins, known to transport glycerol as well as water. AQP3 is the predominant AQP in human skin and has previously been demonstrated in the basal layer of epidermis in normal human skin......, but not in stratum corneum (SC). AQP10 has not previously been identified in human skin. Previous studies have demonstrated the presence of AQP3 and AQP10 mRNA in keratinocytes. In this study, our aim was to investigate if these aquaporin proteins were actually present in human SC cells. This can be seen as a first...... step toward elucidating the possible functional role of AQP3 and AQP10 in SC hydration. Specifically we investigate the presence of AQP3 and AQP10 in vivo in human SC using “minimal-invasive” technique for obtaining SC samples. SC samples were obtained from six healthy volunteers. Western blotting...

  2. Skin hydration: interplay between molecular dynamics, structure and water uptake in the stratum corneum.

    Science.gov (United States)

    Mojumdar, Enamul Haque; Pham, Quoc Dat; Topgaard, Daniel; Sparr, Emma

    2017-11-16

    Hydration is a key aspect of the skin that influences its physical and mechanical properties. Here, we investigate the interplay between molecular and macroscopic properties of the outer skin layer - the stratum corneum (SC) and how this varies with hydration. It is shown that hydration leads to changes in the molecular arrangement of the peptides in the keratin filaments as well as dynamics of C-H bond reorientation of amino acids in the protruding terminals of keratin protein within the SC. The changes in molecular structure and dynamics occur at a threshold hydration corresponding to ca. 85% relative humidity (RH). The abrupt changes in SC molecular properties coincide with changes in SC macroscopic swelling properties as well as mechanical properties in the SC. The flexible terminals at the solid keratin filaments can be compared to flexible polymer brushes in colloidal systems, creating long-range repulsion and extensive swelling in water. We further show that the addition of urea to the SC at reduced RH leads to similar molecular and macroscopic responses as the increase in RH for SC without urea. The findings provide new molecular insights to deepen the understanding of how intermediate filament organization responds to changes in the surrounding environment.

  3. Construction and cellular uptake behavior of redox-sensitive docetaxel prodrug-loaded liposomes.

    Science.gov (United States)

    Ren, Guolian; Jiang, Mengjuan; Guo, Weiling; Sun, Bingjun; Lian, He; Wang, Yongjun; He, Zhonggui

    2018-01-01

    A redox-responsive docetaxel (DTX) prodrug consisting of a disulfide linkage between DTX and vitamin E (DTX-SS-VE) was synthesized in our laboratory and was successfully formulated into liposomes. The aim of this study was to optimize the formulation and investigate the cellular uptake of DTX prodrug-loaded liposomes (DPLs). The content of DTX-SS-VE was determined by ultrahigh-performance liquid chromatography (UPLC). The formulation and process were optimized using entrapment efficiency (EE), drug-loading (DL), particle size and polydispersity index (PDI) as the evaluation indices. The optimal formulation was as follows: drug/lipid ratio of 1:12, cholesterol/lipid ratio of 1:10, hydration temperature of 40 °C, sonication power and time of 400 W and 5 min. The EE, DL and particle size of the optimized DPLs were 97.60 ± 0.03%, 7.09 ± 0.22% and 93.06 ± 0.72 nm, respectively. DPLs had good dilution stability under the physiological conditions over 24 h. In addition, DPLs were found to enter tumor cells via different pathways and released DTX from the prodrug to induce apoptosis. Taken together, the optimized formulation and process were found to be a simple, stable and applicable method for the preparation of DPLs that could successfully escape from lysosomes.

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

    KAUST Repository

    Capriotti, Anna Laura

    2011-07-02

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

  5. Oxygen Measurements in Liposome Encapsulated Hemoglobin

    Science.gov (United States)

    Phiri, Joshua Benjamin

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

  6. Membrane-spanning lipids for an uncompromised monitoring of membrane fusion and intermembrane lipid transfer

    Science.gov (United States)

    Schwarzmann, Günter; Breiden, Bernadette; Sandhoff, Konrad

    2015-01-01

    A Förster resonance energy transfer-based fusion and transfer assay was developed to study, in model membranes, protein-mediated membrane fusion and intermembrane lipid transfer of fluorescent sphingolipid analogs. For this assay, it became necessary to apply labeled reporter molecules that are resistant to spontaneous as well as protein-mediated intermembrane transfer. The novelty of this assay is the use of nonextractable fluorescent membrane-spanning bipolar lipids. Starting from the tetraether lipid caldarchaeol, we synthesized fluorescent analogs with fluorophores at both polar ends. In addition, we synthesized radioactive glycosylated caldarchaeols. These labeled lipids were shown to stretch through bilayer membranes rather than to loop within a single lipid layer of liposomes. More important, the membrane-spanning lipids (MSLs) in contrast to phosphoglycerides proved to be nonextractable by proteins. We could show that the GM2 activator protein (GM2AP) is promiscuous with respect to glycero- and sphingolipid transfer. Saposin (Sap) B also transferred sphingolipids albeit with kinetics different from GM2AP. In addition, we could unambiguously show that the recombinant activator protein Sap C x His6 induced membrane fusion rather than intermembrane lipid transfer. These findings showed that these novel MSLs, in contrast with fluorescent phosphoglycerolipids, are well suited for an uncompromised monitoring of membrane fusion and intermembrane lipid transfer. PMID:26269359

  7. Membrane-spanning lipids for an uncompromised monitoring of membrane fusion and intermembrane lipid transfer.

    Science.gov (United States)

    Schwarzmann, Günter; Breiden, Bernadette; Sandhoff, Konrad

    2015-10-01

    A Förster resonance energy transfer-based fusion and transfer assay was developed to study, in model membranes, protein-mediated membrane fusion and intermembrane lipid transfer of fluorescent sphingolipid analogs. For this assay, it became necessary to apply labeled reporter molecules that are resistant to spontaneous as well as protein-mediated intermembrane transfer. The novelty of this assay is the use of nonextractable fluorescent membrane-spanning bipolar lipids. Starting from the tetraether lipid caldarchaeol, we synthesized fluorescent analogs with fluorophores at both polar ends. In addition, we synthesized radioactive glycosylated caldarchaeols. These labeled lipids were shown to stretch through bilayer membranes rather than to loop within a single lipid layer of liposomes. More important, the membrane-spanning lipids (MSLs) in contrast to phosphoglycerides proved to be nonextractable by proteins. We could show that the GM2 activator protein (GM2AP) is promiscuous with respect to glycero- and sphingolipid transfer. Saposin (Sap) B also transferred sphingolipids albeit with kinetics different from GM2AP. In addition, we could unambiguously show that the recombinant activator protein Sap C x His6 induced membrane fusion rather than intermembrane lipid transfer. These findings showed that these novel MSLs, in contrast with fluorescent phosphoglycerolipids, are well suited for an uncompromised monitoring of membrane fusion and intermembrane lipid transfer. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

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

    Directory of Open Access Journals (Sweden)

    Raquel Martínez-González

    2016-07-01

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

  9. Interaction of Coenzyme Q10 with Liposomes and its Impact on Suppression of Selenite – Induced Experimental Cataract

    Directory of Open Access Journals (Sweden)

    Medhat Wahba Shafaa

    2018-03-01

    Full Text Available Purpose: To stress the influence of Coenzyme Q10 (CoQ10 on the structural properties of liposomes as model membranes and to investigate the possible role of CoQ10 or CoQ10 doped in liposomes when topically instilled as eye drops, in preventing cataract. Methods: The molecular interaction between liposomes and Coenzyme Q10 was examined using differential scanning calorimetry (DSC and Fourier transform infrared spectroscopy (FTIR. Rat pups were randomly divided into six groups comprising 15 pups. Group (1, control group. Group (2, untreated model of cataract, received a single subcutaneous injection of sodium selenite. Instillation of pure CoQ10 (Group 3, CoQ10 encapsulated into neutral (Group 4, positive (Group 5 and negative (Group 6 Dipalmitoyl phosphatidylcholine (DPPC liposomes on the opacification of lenses in rat pups after sodium selenite injection was topically received. Results: The incorporated CoQ10 is probably associated with lipid bilayers where it interacts to a large extent and perturbs them. This results in strong broadening and shift to lower temperature (94°C of the major characteristic endothermic peak of pure DPPC at 105°C. FTIR showed that the incorporation of CoQ10 into DPPC induces a conformational change in the polar region of DPPC. Ophthalmological and Biochemical studies revealed that CoQ10 alone followed by negatively charged liposomes doped with CoQ10 are more effective in reducing the progress of cataract as well as improving the lens soluble proteins levels and total antioxidant capacity. Conclusion: The interactions of CoQ10 with membrane systems may contribute to a better understanding of CoQ10 physiological properties and the development of therapeutically advanced systems.

  10. Photo activation of HPPH encapsulated in “Pocket” liposomes triggers multiple drug release and tumor cell killing in mouse breast cancer xenografts

    Directory of Open Access Journals (Sweden)

    Sine J

    2014-12-01

    Full Text Available Jessica Sine,1,* Cordula Urban,2,* Derek Thayer,1 Heather Charron,2 Niksa Valim,2 Darrell B Tata,3 Rachel Schiff,4 Robert Blumenthal,1 Amit Joshi,2 Anu Puri1 1Membrane Structure and Function Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute – Frederick, Frederick, MD, USA; 2Department of Radiology, Baylor College of Medicine, Houston, TX, USA; 3US Food and Drug Administration, CDRH/OSEL/Division of Physics, White Oak Campus, MD, USA; 4Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA *These authors contributed equally to this work Abstract: We recently reported laser-triggered release of photosensitive compounds from liposomes containing dipalmitoylphosphatidylcholine (DPPC and 1,2 bis(tricosa-10,12-diynoyl-sn-glycero-3-phosphocholine (DC8,9PC. We hypothesized that the permeation of photoactivated compounds occurs through domains of enhanced fluidity in the liposome membrane and have thus called them “Pocket” liposomes. In this study we have encapsulated the red light activatable anticancer photodynamic therapy drug 2-(1-Hexyloxyethyl-2-devinyl pyropheophorbide-a (HPPH (Ex/Em410/670 nm together with calcein (Ex/Em490/517 nm as a marker for drug release in Pocket liposomes. A mole ratio of 7.6:1 lipid:HPPH was found to be optimal, with >80% of HPPH being included in the liposomes. Exposure of liposomes with a cw-diode 660 nm laser (90 mW, 0–5 minutes resulted in calcein release only when HPPH was included in the liposomes. Further analysis of the quenching ratios of liposome-entrapped calcein in the laser treated samples indicated that the laser-triggered release occurred via the graded mechanism. In vitro studies with MDA-MB-231-LM2 breast cancer cell line showed significant cell killing upon treatment of cell-liposome suspensions with the laser. To assess in vivo efficacy, we implanted MDA-MB-231-LM2 cells containing the luciferase gene along the mammary fat pads

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

    Science.gov (United States)

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

    2008-02-01

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

  12. Using membrane composition to fine-tune the pKa of an optical liposome pH sensor.

    Science.gov (United States)

    Clear, Kasey J; Virga, Katelyn; Gray, Lawrence; Smith, Bradley D

    2016-04-14

    Liposomes containing membrane-anchored pH-sensitive optical probes are valuable sensors for monitoring pH in various biomedical samples. The dynamic range of the sensor is maximized when the probe p K a is close to the expected sample pH. While some biomedical samples are close to neutral pH there are several circumstances where the pH is 1 or 2 units lower. Thus, there is a need to fine-tune the probe p K a in a predictable way. This investigation examined two lipid-conjugated optical probes, each with appended deep-red cyanine dyes containing indoline nitrogen atoms that are protonated in acid. The presence of anionic phospholipids in the liposomes stabilized the protonated probes and increased the probe p K a values by sensor for optimal pH sensing performance.

  13. Microsomal lipid peroxidation as a mechanism of cellular damage. [Dissertation

    Energy Technology Data Exchange (ETDEWEB)

    Kornbrust, D.J.

    1979-01-01

    The NADPH/iron-dependent peroxidation of lipids in rat liver microsomes was found to be dependent on the presence of free ferrous ion and maintains iron in the reduced Fe/sup 2 +/ state. Chelation of iron by EDTA inhibited peroxidation. Addition of iron, after preincubation of microsomes in the absence of iron, did not enhance the rate of peroxidation suggesting that iron acts by initiating peroxidative decomposition of membrane lipids rather than by catalyzing the breakdown of pre-formed hydroperoxides. Liposomes also underwent peroxidation in the presence of ferrous iron at a rate comparable to intact microsomes and was stimulated by ascorbate. Carbon tetrachloride initiated lipid peroxidation in the absence of free metal ions. Rates of in vitro lipid peroxidation of microsomes and homogenates were found to vary widely between different tissues and species. The effects of paraquat on lipid peroxidation was also studied. (DC)

  14. SAXS Study of Sterically Stabilized Lipid Nanocarriers Functionalized by DNA

    Science.gov (United States)

    Angelov, Borislav; Angelova, Angelina; Filippov, Sergey; Karlsson, Göran; Terrill, Nick; Lesieur, Sylviane; Štěpánek, Petr

    2012-03-01

    The structure of novel spontaneously self-assembled plasmid DNA/lipid complexes is investigated by means of synchrotron radiation small-angle X-ray scattering (SAXS) and Cryo-TEM imaging. Liquid crystalline (LC) hydrated lipid systems are prepared using the non-ionic lipids monoolein and DOPE-PEG2000 and the cationic amphiphile CTAB. The employed plasmid DNA (pDNA) is encoding for the human protein brain-derived neurotrophic factor (BDNF). A coexistence of nanoparticulate objects with different LC inner organizations is established. A transition from bicontinuous membrane sponges, cubosome intermediates and unilamelar liposomes to multilamellar vesicles, functionalized by pDNA, is favoured upon binding and compaction of pBDNF onto the cationic PEGylated lipid nanocarriers. The obtained sterically stabilized multicompartment nanoobjects, with confined supercoiled plasmid DNA (pBDNF), are important in the context of multicompartment lipid nanocarriers of interest for gene therapy of neurodegenerative diseases.

  15. SAXS Study of Sterically Stabilized Lipid Nanocarriers Functionalized by DNA

    International Nuclear Information System (INIS)

    Angelov, Borislav; Filippov, Sergey; Štepánek, Petr; Angelova, Angelina; Lesieur, Sylviane; Karlsson, Göran; Terrill, Nick

    2012-01-01

    The structure of novel spontaneously self-assembled plasmid DNA/lipid complexes is investigated by means of synchrotron radiation small-angle X-ray scattering (SAXS) and Cryo-TEM imaging. Liquid crystalline (LC) hydrated lipid systems are prepared using the non-ionic lipids monoolein and DOPE-PEG 2000 and the cationic amphiphile CTAB. The employed plasmid DNA (pDNA) is encoding for the human protein brain-derived neurotrophic factor (BDNF). A coexistence of nanoparticulate objects with different LC inner organizations is established. A transition from bicontinuous membrane sponges, cubosome intermediates and unilamelar liposomes to multilamellar vesicles, functionalized by pDNA, is favoured upon binding and compaction of pBDNF onto the cationic PEGylated lipid nanocarriers. The obtained sterically stabilized multicompartment nanoobjects, with confined supercoiled plasmid DNA (pBDNF), are important in the context of multicompartment lipid nanocarriers of interest for gene therapy of neurodegenerative diseases.

  16. Determination of the influence of C24 D/(2R)- and L/(2S)-isomers of the CER[AP] on the lamellar structure of stratum corneum model systems using neutron diffraction.

    Science.gov (United States)

    Schmitt, Thomas; Lange, Stefan; Sonnenberger, Stefan; Dobner, Bodo; Demé, Bruno; Neubert, Reinhard H H; Gooris, Gert; Bouwstra, Joke A

    2017-12-01

    This study was able to investigate the different influence of the d- and l-ceramide [AP] on the lamellar as well as molecular nanostructure of stratum corneum simulating lipid model mixtures. In this case, neutron diffraction together with specifically deuterated ceramide was used as an effective tool to investigate the lamellar and the molecular nanostructure of the mixtures. It could clearly be demonstrated, that both isomers show distinctly different characteristics, even though the variation between both is only a single differently arranged OH-group. The l-ceramide [AP] promotes a crystalline like phase behaviour even if mixed with ceramide [NP], cholesterol and free fatty acids. The d-ceramide [AP] only shows crystalline-like features if mixed only with cholesterol and free fatty acids but adopts a native-like behaviour if additionally mixed with ceramide [NP]. It furthermore demonstrates that the l-ceramide [AP] should not be used for any applications concerning ceramide substitution. It could however possibly serve its own purpose, if this crystalline like behaviour has some kind of positive influence on the SC or can be utilized for any practical applications. The results obtained in this study demonstrate that the diastereomers of ceramide [AP] are an attractive target for further research because their influence on the lamellar as well as the nanostructure is exceptionally strong. Additionally, the results furthermore show a very strong influence on hydration of the model membrane. With these properties, the d-ceramide [AP] could be effectively used to simulate native like behaviour even in very simple mixtures and could also have a strong impact on the native stratum corneum as well as high relevance for dermal ceramide substitution. The unnatural l-ceramide [AP] on the other hand should be investigated further, to assess its applicability. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. [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