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Sample records for a2 degradable liposomal

  1. Secretory Phospholipase A2 Responsive Liposomes

    PubMed Central

    ZHU, GUODONG; MOCK, JASON N.; ALJUFFALI, IBRAHIM; CUMMINGS, BRIAN S.; ARNOLD, ROBERT D.

    2011-01-01

    Secretory phospholipase A2 (sPLA2) expression is increased in several cancers and has been shown to trigger release from some lipid carriers. This study used electrospray ionization mass spectrometry (ESI-MS) and release of 6-carboxyfluorescein (6-CF) to determine the effects of sPLA2 on various liposome formulations. Different combinations of zwitterionic [1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine, 1,2-distearoyl-sn-glycero-3-phosphatidylcholine, and 1,2- distearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE)] and anionic [1,2-distearoyl-sn-glycero-3-phosphatidic acid, 1,2-distearoyl-sn-glycero-3-phosphatidylglycerol (DSPG), 1,2-distearoyl-sn-glycero-3-phosphatidylserine, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine–N-poly(ethylene glycol) 2000 (DSPE–PEG)] phospholipids were examined. DSPG and DSPE were most susceptible to sPLA2-mediated degradation compared with other phospholipids. Increased 6-CF release was observed after inclusion of 10 mol % DSPE and anionic lipids into different liposome formulations. Group IIa sPLA2-mediated 6-CF release was less than Group III and relatively insensitive to cholesterol (Chol), whereas Chol reduced sPLA2-mediated release. Inclusion of DSPE–PEG increased sPLA2-mediated 6-CF release, whereas serum reduced lipid degradation and 6-CF release significantly. These data demonstrate that ESI-MS and 6-CF release were useful in determining the selectivity of sPLA2 and release from liposomes, that differences in the activity of different sPLA2 isoforms exist, and that DSPE–PEG enhanced sPLA2-mediated release of liposomal constituents. These findings will aid in the selection of lipids and optimization of the kinetics of drug release for the treatment of cancers and diseases of inflammation in which sPLA2 expression is increased. PMID:21455978

  2. Influence of lipopolymer concentration on liposome degradation and blood clearance.

    PubMed

    Vermehren, C; Jørgensen, K; Frokjaer, S

    1999-06-10

    It is well known, that a prolonged liposome circulation time can be achieved by incorporation of lipopolymers into the lipid membrane thereby reducing interactions with destabilizing factors in the blood stream, e.g. phagocytic cells and lipoproteins. However, very little is known about the enzymatic degradation of steric hindered liposomes introduced into body fluids. In this study, the blood clearance and the PLA2 catalyzed degradation of unilamellar dipalmitoylphosphatidylcholine (DPPC) liposomes incorporated with increasing amounts of dipalmitoylphosphatidylethanolamine-polyethyleneglycol (DPPE-PEG), was investigated. The results demonstrated an increase in PLA2 activity for increasing amounts of lipopolymer in the lipid membrane, while the liposome blood clearance was prolonged by incorporation of DPPE-PEG into the liposomes. Hence, these results suggest that it may be possible for long circulating liposomes to obtain a site specific liposome degradation and release of drug substance in tissue with high levels of PLA2.

  3. Activity of mammalian secreted phospholipase A(2) from inflammatory peritoneal fluid towards PEG-liposomes. Early indications.

    PubMed

    Vermehren, C; Jørgensen, K; Schiffelers, R; Frokjaer, S

    2001-02-19

    Due to an increase in the activity of phospholipase A(2) (PLA(2)) in various inflammatory diseases, this enzyme may play a key role in the degradation of liposomes and the subsequent release of drug when PEG-liposomes passively target inflammatory tissue. The activity of mammalian secreted phospholipase A(2) (sPLA(2)) in casein stimulated peritoneal fluid was tested toward liposomes of different compositions. Early results indicate only a slight degradation of conventional dipalmitoylphosphatidylcholine (DPPC) liposomes as well as DPPC liposomes incorporated with different concentrations of PEG(2000). However, the DPPC degradation increased to 7% when inclusion of 30 mol% phosphatidylethanolamine (PE) in the lipid bilayer. The increase in degradation may be due to an improvement of the substrate - as it is well known, that PE is a better substrate for the mammalian sPLA(2) than PC. Incorporation of PE into the bilayer may increase the binding properties of the bilayer resulting in improved conditions for the enzymatic attack by sPLA(2). In addition, inhibitory zones of Staphylococcus aureus in an agar diffusion test showed that PLA(2) from Crotalus atrox venom was able to catalyze the release of gentamicin from PEG-liposomes. In conclusion, this study suggest that degradation of the lipid bilayer of PEG-liposomes by PLA(2) result in release of incapsulated drug, e.g. gentamicin and inclusion of PE in the liposomal bilayer, may enhance the activity of the mammalian sPLA(2) toward liposomes composed of DPPC.

  4. Increase in phospholipase A2 activity towards lipopolymer-containing liposomes.

    PubMed

    Vermehren, C; Kiebler, T; Hylander, I; Callisen, T H; Jørgensen, K

    1998-08-14

    Phospholipase A2 (PLA2)-catalyzed hydrolysis of dipalmitoylphosphatidylcholine (DPPC) liposomes incorporated with submicellar concentrations of polyethyleneoxide covalently attached to dipalmitoylphosphatidylethanolamine (DPPE-PEG2000) has been studied in the gel-to-fluid transition region of the host DPPC lipid bilayer matrix. By means of fluorescence and light-scattering measurements, the characteristic PLA2 lag time has been determined as a function of lipopolymer concentration and temperature. The degree of lipid hydrolysis was followed using radioactive labeled lipids. Differential scanning calorimetry has been applied to characterize the thermodynamic phase behavior of the lipopolymer-containing liposomes. A remarkable lipopolymer concentration-dependent decrease in the lag time was observed over broad temperature ranges. The radioactive measurements demonstrate an increase in catalytic activity for increasing amounts of lipopolymers in the bilayer. Hence, the lipopolymers act as a promoter of PLA2 lipid hydrolysis resulting in a degradation of the bilayer structure and a concomitant destabilization of the liposomes. This behavior is in contrast to the generally observed protective and stabilization effect in biological fluids exerted by lipopolymers in polymer-grafted liposomes. It is proposed that the enhanced activity of the small water soluble and interfacially active enzyme may involve a non-uniform distribution of the lipopolymers in the lipid matrix due to a coupling between local lipid bilayer curvature and composition of the non-bilayer-preferring lipopolymers.

  5. Hepatic uptake and degradation of unilamellar sphingomyelin/cholesterol liposomes: a kinetic study.

    PubMed Central

    Hwang, K J; Luk, K F; Beaumier, P L

    1980-01-01

    The kinetics of hepatic uptake and degradation of sphingomyelin/cholesterol (2:1, M/M) small unilamellar liposomes were investigated in a BALB/c mouse. The tissue distribution of liposomes was determined by scintillation spectrometry. The percentage of intact liposomes in tissues was estimated by the technique of gamma-ray perturbed angular correlation. A kinetic model was developed to analyze the above data. A remarkable agreement was noted between the experimental data and the corresponding theoretical values. Our results indicate that the sphingomyelin/cholesterol unilamellar liposomes had an unusually long half-life of 16.5 hr in the circulation after intravenous administration to mice. The hepatic degradation of the liposomes in vitro at 37 degrees C followed first-order kinetics, with a half-life of 3.5 +/- 0.2 (SEM) hr. Furthermore, the rate of the in vivo degradation of liposomes in the liver was found to be quite similar to that in vitro, with a half-life of 3.6 +/- 0.4 hr. The rate of release of the liposome-encapsulated agent, indium-111, in the liver was not constant, and reached a maximum at about 8 hr after the administration of liposomes. The approach developed in the present study is general and can be applied to the investigation of factors that may control the release of pharmacologically active agents in any tissue. PMID:6933450

  6. In vivo oxalate degradation by liposome encapsulated oxalate oxidase in rat model of hyperoxaluria

    PubMed Central

    Dahiya, Tulika; Pundir, C.S.

    2013-01-01

    Background & objectives: High level of urinary oxalate substantially increases the risk of hyperoxaluria, a significant risk factor for urolithiasis. The primary goal of this study was to reduce urinary oxalate excretion employing liposome encapsulated oxalate oxidase in animal model. Methods: A membrane bound oxalate oxidase was purified from Bougainvillea leaves. The enzyme in its native form was less effective at the physiological pH of the recipient animal. To increase its functional viability, the enzyme was immobilized on to ethylene maleic anhydride (EMA). Rats were injected with liposome encapsulated EMA- oxalate oxidase and the effect was observed on degradation of oxalic acid. Results: The enzyme was purified to apparent homogeneity with 60-fold purification and 31 per cent yield. The optimum pH of EMA-derivative enzyme was 6.0 and it showed 70 per cent of its optimal activity at pH 7.0. The EMA-bound enzyme encapsulated into liposome showed greater oxalate degradation in 15 per cent casein vitamin B6 deficient fed rats as compared with 30 per cent casein vitamin B6 deficient fed rats and control rats. Interpretation & conclusions: EMA-oxalate oxidase encapsulated liposome caused oxalate degradation in experimental hyperoxaluria indicating that the enzyme could be used as a therapeutic agent in hyperoxaluria leading to urinary stones. PMID:23481063

  7. Liposomes.

    PubMed

    Posner, Robert

    2002-09-01

    Robert Posner has 40 years of experience in skin care bench chemistry, product development, and sales and marketing. Working closely with dermatologists and plastic surgeons, Posner is a former member of the NY State Hospital Pharmacists Association, the American Pharmaceutical Association, and the American Association of Hospital Pharmacists. Currently, Posner sits on the Board of Directors of EMDA (Esthetic Manufacturers and Distributors Association). Posner has written numerous articles for Les Nouvelles Esthetiques Magazine, is presently a consultant for Day Spa Magazine, and had been one of only two non-dermatologists on a consultant basis with Cosmetic Dermatology Journal. Posner's company--ABBE Cosmetic Group International in Farmingdale, NY--formulates and manufactures skin care products for many well-known companies in the beauty industry. For many years, both the bench chemist and the dermatologist have been concerned with developing an ideal base for deliverance of 'actives' to the human epidermis. As is common knowledge, the skin is a protective organ which allows very few materials to penetrate. Some bases are unable to work effectively because of their relative inability to penetrate the stratum corneum; for example, some notable actives such as collagen and elastin are molecules too large to penetrate effectively. With the liposome at our command however, we can carry and then release an active into several layers of epidermis. We can release both oil- and water-soluble actives, and at the same time control the feel and effectiveness of a topical application. This article will examine the liposome: what it is, how it works, and how products made with liposomes can benefit dermatology.

  8. Influence of Endosomal Escape and Degradation of α-Galactosylceramide Loaded Liposomes on CD1d Antigen Presentation.

    PubMed

    Nakamura, Takashi; Kuroi, Moeka; Harashima, Hideyoshi

    2015-08-03

    Alpha-galactosylceramide (GC), a lipid antigen present on CD1d molecules, is a unique adjuvant that enables a strong antitumor effect to be induced via activation of natural killer T cells. We previously reported that a liposomal formulation of GC significantly enhanced GC presentation via CD1d and antitumor immunity. However, the influence of the intracellular fate of liposomes controlled by the lipid composition on GC presentation using GC-loaded liposomes (GC-Lip) remains unclear. In this study, we prepared a GC-Lip formulation by incorporating dioleoyl-phosphatidylethanolamine (DOPE)/cholesterol, egg phosphatidylcholine (EPC)/cholesterol, and distearoyl phosphocholine (DSPC)/cholesterol, and investigated the relationship between the intracellular trafficking of GC-Lip and GC presentation in antigen-presenting cells. When GC-Lip was prepared using DOPE, a fusogenic lipid, the endosomal escape of liposomes was enhanced, resulting in a decrease in GC presentation of CD1d, compared to the EPC based GC-Lip (EPC/GC-Lip). The stability of liposomes in endosomes/lysosomes had no influence on GC presentation. The DSPC based GC-Lip (DSPC/GC-Lip) induced GC presentation without any detectable degradation in liposomal structure, although the EPC/GC-Lip induced GC presentation with degradation of liposomal structure. The efficiency of GC presentation between EPC/GC-Lip and DSPC/GC-Lip was comparable. These GC presentations that were independent of the degradation of liposomes were dominated by saposins, sphingolipid activator proteins. Our findings reveal that GC presentation on CD1d from the fluid liposomes involves the action of saposins, regardless of whether liposome degradation occurs. This insight can be of use in terms of developing GC-Lip formulation for efficient GC presentation.

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

    PubMed Central

    Niu, Mengmeng; Lu, Yi; Hovgaard, Lars; Wu, Wei

    2011-01-01

    Background: Oral delivery of insulin is challenging and must overcome the barriers of gastric and enzymatic degradation as well as low permeation across the intestinal epithelium. The present study aimed to develop a liposomal delivery system containing glycocholate as an enzyme inhibitor and permeation enhancer for oral insulin delivery. Methods: Liposomes containing sodium glycocholate were prepared by a reversed-phase evaporation method followed by homogenization. The particle size and entrapment efficiency of recombinant human insulin (rhINS)-loaded sodium glycocholate liposomes can be easily adjusted by tuning the homogenization parameters, phospholipid:sodium glycocholate ratio, insulin:phospholipid ratio, water:ether volume ratio, interior water phase pH, and the hydration buffer pH. Results: The optimal formulation showed an insulin entrapment efficiency of 30% ± 2% and a particle size of 154 ± 18 nm. A conformational study by circular dichroism spectroscopy and a bioactivity study confirmed the preserved integrity of rhINS against preparative stress. Transmission electron micrographs revealed a nearly spherical and deformed structure with discernable lamella for sodium glycocholate liposomes. Sodium glycocholate liposomes showed better protection of insulin against enzymatic degradation by pepsin, trypsin, and α-chymotrypsin than liposomes containing the bile salt counterparts of sodium taurocholate and sodium deoxycholate. Conclusion: Sodium glycocholate liposomes showed promising in vitro characteristics and have the potential to be able to deliver insulin orally. PMID:21822379

  10. Quantum dot-NBD-liposome luminescent probes for monitoring phospholipase A2 activity.

    PubMed

    Kethineedi, Venkata R; Crivat, Georgeta; Tarr, Matthew A; Rosenzweig, Zeev

    2013-12-01

    In this paper we describe the fabrication and characterization of new liposome encapsulated quantum dot-fluorescence resonance energy transfer (FRET)-based probes for monitoring the enzymatic activity of phospholipase A2. To fabricate the probes, luminescent CdSe/ZnS quantum dots capped with trioctylphosphine oxide (TOPO) ligands were incorporated into the lipid bilayer of unilamellar liposomes with an average diameter of approximately 100 nm. Incorporating TOPO capped quantum dots in liposomes enabled their use in aqueous solution while maintaining their hydrophobicity and excellent photophysical properties. The phospholipid bilayer was labeled with the fluorophore NBD C6-HPC (2-(6-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoyl-1-hexa decanoyl-sn-glycero-3-phosphocholine). The luminescent quantum dots acted as FRET donors and the NBD dye molecules acted as FRET acceptors. The probe response was based on FRET interactions between the quantum dots and the NBD dye molecules. The NBD dye molecules were cleaved and released to the solution in the presence of the enzyme phospholipase A2. This led to an increase of the luminescence of the quantum dots and to a corresponding decrease in the fluorescence of the NBD molecules, because of a decrease in FRET efficiency between the quantum dots and the NBD dye molecules. Because the quantum dots were not attached covalently to the phospholipids, they did not hinder the enzyme activity as a result of steric effects. The probes were able to detect amounts of phospholipase A2 as low as 0.0075 U mL(-1) and to monitor enzyme activity in real time. The probes were also used to screen phospholipase A2 inhibitors. For example, we found that the inhibition efficiency of MJ33 (1-hexadecyl-3-(trifluoroethyl)-sn-glycero-2-phosphomethanol) was higher than that of OBAA (3-(4-octadecyl)benzoylacrylic acid).

  11. Monitoring Phospholipase A2 Activity with Gd-encapsulated Phospholipid Liposomes

    PubMed Central

    Cheng, Zhiliang; Tsourkas, Andrew

    2014-01-01

    To date, numerous analytical methods have been developed to monitor phospholipase A2 (PLA2) activity. However, many of these methods require the use of unnatural PLA2 substrates that may alter enzyme kinetics, and probes that cannot be extended to applications in more complex environments. It would be desirable to develop a versatile assay that monitors PLA2 activity based on interactions with natural phospholipids in complex biological samples. Here, we developed an activatable T1 magnetic resonance (MR) imaging contrast agent to monitor PLA2 activity. Specifically, the clinically approved gadolinium (Gd)-based MR contrast agent, gadoteridol, was encapsulated within nanometer-sized phospholipid liposomes. The encapsulated Gd exhibited a low T1-weighted signal, due to low membrane permeability. However, when the phospholipids within the liposomal membrane were hydrolyzed by PLA2, encapsulated Gd was released into bulk solution, resulting in a measureable change in the T1-relaxation time. These activatable MR contrast agents can potentially be used as nanosensors for monitoring of PLA2 activity in biological samples with minimal sample preparation. PMID:25376186

  12. Degradation kinetics of water-insoluble lauroyl-indapamide in aqueous solutions: prediction of the stabilities of the drug in liposomes.

    PubMed

    Suo, Xu Bin; Deng, Ying Jie; Zhang, Han; Wang, Yu Qiang

    2007-07-01

    The aim of this study was to explore the degradation kinetics of water-insoluble lauroyl-indapamide in solutions and predict the stabilities of lauroyl-indapamide encapsulated in liposomes. Buffer-acetone (9:1) was used as the reaction solution and the reaction temperature was maintained at 60 degrees C. The correlation of the apparent degradation constants (k(obs)) of lauroyl-indapamide in liposomes and in buffer-acetone solutions at different pH has been explored. The degradation of lauroyl-indapamide in solutions was found to follow pseudo-first-order kinetics and was significantly dependent on the pH values. Lauroyl-indapamide was the most stable at pH 6.8, increasing or decreasing the pH of the solutions would decrease its stabilities. Buffer concentration had some effects on the stabilities of lauroyl-indapamide. The degradation active energies Ea were 68.19 kJ x mol(-1), 131.75 kJ x mol(-1) and 107.72 kJ x mol(-1) at pH3.6, 6.8 and 12 respectively in acetone-free buffer solutions (0.05M) calculated according to the Arrhenius equation with the extrapolation method. The apparent degradation constants (kobs) of lauroyl-indapamide in liposome and in buffer-acetone (9:1) solutions showed a good correlation at different pH levels, which indicates that the stabilities of the drug that dissolved in acetone-buffer mixture solutions can be used to predict the stabilities of the drug in liposomes as well.

  13. Cationic liposomes promote antigen cross-presentation in dendritic cells by alkalizing the lysosomal pH and limiting the degradation of antigens.

    PubMed

    Gao, Jie; Ochyl, Lukasz J; Yang, Ellen; Moon, James J

    2017-01-01

    Cationic liposomes (CLs) have been widely examined as vaccine delivery nanoparticles since they can form complexes with biomacromolecules, promote delivery of antigens and adjuvant molecules to antigen-presenting cells (APCs), and mediate cellular uptake of vaccine components. CLs are also known to trigger antigen cross-presentation - the process by which APCs internalize extracellular protein antigens, degrade them into minimal CD8(+) T-cell epitopes, and present them in the context of major histocompatibility complex-I (MHC-I). However, the precise mechanisms behind CL-mediated induction of cross-presentation and cross-priming of CD8(+) T-cells remain to be elucidated. In this study, we have developed two distinct CL systems and examined their impact on the lysosomal pH in dendritic cells (DCs), antigen degradation, and presentation of peptide:MHC-I complexes to antigen-specific CD8(+) T-cells. To achieve this, we have used 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as the prototypical components of CLs with tertiary amine groups and compared the effect of CLs and anionic liposomes on lysosomal pH, antigen degradation, and cross-presentation by DCs. Our results showed that CLs, but not anionic liposomes, elevated the lysosomal pH in DCs and reduced antigen degradation, thereby promoting cross-presentation and cross-priming of CD8(+) T-cell responses. These studies shed new light on CL-mediated cross-presentation and suggest that intracellular fate of vaccine components and subsequent immunological responses can be controlled by rational design of nanomaterials.

  14. Cationic liposomes promote antigen cross-presentation in dendritic cells by alkalizing the lysosomal pH and limiting the degradation of antigens

    PubMed Central

    Gao, Jie; Ochyl, Lukasz J; Yang, Ellen; Moon, James J

    2017-01-01

    Cationic liposomes (CLs) have been widely examined as vaccine delivery nanoparticles since they can form complexes with biomacromolecules, promote delivery of antigens and adjuvant molecules to antigen-presenting cells (APCs), and mediate cellular uptake of vaccine components. CLs are also known to trigger antigen cross-presentation – the process by which APCs internalize extracellular protein antigens, degrade them into minimal CD8+ T-cell epitopes, and present them in the context of major histocompatibility complex-I (MHC-I). However, the precise mechanisms behind CL-mediated induction of cross-presentation and cross-priming of CD8+ T-cells remain to be elucidated. In this study, we have developed two distinct CL systems and examined their impact on the lysosomal pH in dendritic cells (DCs), antigen degradation, and presentation of peptide:MHC-I complexes to antigen-specific CD8+ T-cells. To achieve this, we have used 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as the prototypical components of CLs with tertiary amine groups and compared the effect of CLs and anionic liposomes on lysosomal pH, antigen degradation, and cross-presentation by DCs. Our results showed that CLs, but not anionic liposomes, elevated the lysosomal pH in DCs and reduced antigen degradation, thereby promoting cross-presentation and cross-priming of CD8+ T-cell responses. These studies shed new light on CL-mediated cross-presentation and suggest that intracellular fate of vaccine components and subsequent immunological responses can be controlled by rational design of nanomaterials. PMID:28243087

  15. Liposomal honokiol induced lysosomal degradation of Hsp90 client proteins and protective autophagy in both gefitinib-sensitive and gefitinib-resistant NSCLC cells.

    PubMed

    Yang, Jianhong; Wu, Wenshuang; Wen, Jiaolin; Ye, Haoyu; Luo, Hong; Bai, Peng; Tang, Minghai; Wang, Fang; Zheng, Li; Yang, Shengyong; Li, Weimin; Peng, Aihua; Yang, Li; Wan, Li; Chen, Lijuan

    2017-10-01

    Honokiol (HK), a natural chemical isolated from Mangnolia officinalis, has shown antitumorigenic activities when used to treat a variety of tumor cell lines. The mechanism of honokiol activity when used to treat gefitinib-sensitive and gefitinib-resistant non-small cell lung cancer (NSCLC) requires elucidation. Here, the presence of liposomal honokiol (LHK) induced apoptotic and antitumor activities in four xenograft models generated using NSCLC cell lines such as HCC827 (gefitinib-sensitive) and H1975 (gefitinib-resistant). Mechanistic studies revealed that LHK inhibited the Akt and Erk1/2, both EGFR signaling cascades effectors, by promoting degradation of HSP90 client proteins (HCP), including wild-type or mutant EGFR, Akt and C-Raf. Molecular biology assays showed that LHK induced HCP degradation through a lysosomal pathway, rather than the canonical proteasome protein degradation pathway. As a result of misfolded protein accumulation, LHK induced endoplasmic reticulum (ER) stress and autophagy. Inhibition of ER stress (with 4-phenylbutyrate) or autophagy (with small interfering RNA) reduced LHK-induced HCP degradations. Additionally, LHK induced autophagy showed a protective role for cancer cell as inhibition of autophagy in vitro and in vivo by autophagosome degradation inhibitors could promote the anticancer activity of LHK. LHK has been approved by the China Food and Drug Administration for first-in-human clinical trials in NSCLC. The current study will guide the design of future LHK clinical trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Liposomal chemotherapeutics.

    PubMed

    Gentile, Emanuela; Cilurzo, Felisa; Di Marzio, Luisa; Carafa, Maria; Ventura, Cinzia Anna; Wolfram, Joy; Paolino, Donatella; Celia, Christian

    2013-12-01

    Currently, six liposomal chemotherapeutics have received clinical approval and many more are in clinical trials or undergoing preclinical evaluation. Liposomes exhibit low toxicity and improve the biopharmaceutical features and therapeutic index of drugs, thereby increasing efficacy and reducing side effects. In this review we discuss the advantages of using liposomes for the delivery of chemotherapeutics. Gemcitabine and paclitaxel have been chosen as examples to illustrate how the performance of a metabolically unstable or poorly water-soluble drug can be greatly improved by liposomal incorporation. We look at the beneficial effects of liposomes in a variety of solid and blood-borne tumors, including thyroid cancer, pancreatic cancer, breast cancer and multiple myeloma.

  17. Gene delivery using liposome technology.

    PubMed

    Kikuchi, H; Suzuki, N; Ebihara, K; Morita, H; Ishii, Y; Kikuchi, A; Sugaya, S; Serikawa, T; Tanaka, K

    1999-11-01

    Development of more reliable liposomal formulations and preparation methods which can be used for gene therapy instead of commonly used viral vectors is expected. We have already developed the freeze-dried empty (non-drug-containing) liposomes (FDEL) method for mass-production of liposomal products. After these freeze-dried empty liposomes are rehydrated with aqueous drug solutions, many kinds of drugs can be encapsulated highly efficiently, and particle size can be controlled well. This study evaluated the usefulness of this FDEL method for preparation of liposomes containing DNA with a particular attention to the stability of DNA. When the liposomes were prepared by the conventional lipid-film method on a relatively large scale with use of a Potter-homogenizer (a teflon homogenizer), significant degradation and conformational change of DNA was observed during homogenization. Loss of DNA was also significant after extrusion for sizing and sterilization; residual DNA in the final preparation was hardly detected. When the FDEL method was used, on the other hand, no degradation, conformational change or loss of DNA was observed, and particle size was easily controlled. Moreover, there was no significant difference in luciferase activity between the lipid-film method used on a small scale with use of a vortex mixer and the FDEL method after transfection of tumor cells (HRA, HEC-1A and Colo320DM) by the liposomes containing DNA (PGV-C). These findings suggest that the FDEL method is very useful for preparation of liposomes containing DNA.

  18. Sequential injection system for phospholipase A2 activity evaluation: studies on liposomes using an environment-sensitive fluorescent probe.

    PubMed

    Araujo, André R T S; Gaspar, Diana; Lúcio, Marlene; Reis, Salette; Saraiva, M Lúcia M F S; Lima, José L F C

    2009-09-15

    This work reports the development of an automatic methodology based on the use of 1-anilinonaphthalene-8-sulfonate (ANS) as an interfacial fluorescent probe for detecting the hydrophobic environment shift around the probe, caused by the hydrolytic action of PLA(2) on the liposomes. The implementation of this reaction in a sequential injection analysis (SIA) system along with the use of the mixing chambers permitted the evaluation of PLA(2) activity and assessment of the inhibitory effect of the non-steroidal anti-inflammatory drugs (NSAIDs) on PLA(2) activity. Several studies were performed with the aim of establishing the appropriate flow system configuration: the liposome substrate; PLA(2) and ANS optimum concentrations and incubation times before and after the enzyme addition. Based on these studies, the optimum reaction conditions were selected. It was shown that PLA(2) is effectively inhibited by the NSAIDs tested (meloxicam, tolmetin and ibuprofen) and by the alpha-lipoic acid, used as a positive control. Results obtained from the flow system are in agreement with those provided by the comparison batch procedures. The proposed methodology is in fact more efficient and rapid than the comparison batch experiments, enabling the exact timing of fluidic manipulations and precise control of the reaction conditions.

  19. Interaction of a lipid-membrane destabilizing enzyme with PEG-liposomes.

    PubMed

    Jørgensen, K; Kiebler, T; Hylander, I; Vermehren, C

    1999-06-10

    Polymer grafted PEG-liposomes have come into use as drug-delivery systems with improved therapeutic profiles. However, very little is known about the morphological instability of PEG-liposomes due to enzymatic degradation. To gain further insight into the effect of PEG lipopolymer-concentration on the catalytic activity of a liposome-degrading enzyme, phospholipase A2 (PLA2)-catalyzed phospholipid hydrolysis of PEG-liposomes has been investigated. The temperature dependence of the PLA2 lag-time, denoting the time required before a sudden increase in enzymatic activity takes place, has been determined for submicellar amounts of dipalmitoylphosphatidylethanolaminyl-poly-(ethylene glycol) (DPPE-PEG2000) incorporated into unilamellar dipalmitoylphosphatidylcholine (DPPC)-liposomes. The measurements demonstrate a significant reduction in the lag-time over broad temperature ranges. The results suggest that a close relationship exists between PLA2 catalyzed lipid hydrolysis and lipid-membrane composition, which moreover is of major importance for the overall morphological stability and the release of encapsulated material from the polymer-grafted PEG-liposomes.

  20. Doped colorimetric assay liposomes

    DOEpatents

    Charych, Deborah; Stevens, Raymond C.

    2001-01-01

    The present invention provides compositions comprising colorimetric assay liposomes. The present invention also provides methods for producing colorimetric liposomes and calorimetric liposome assay systems. In preferred embodiments, these calorimetric liposome systems provide high levels of sensitivity through the use of dopant molecules. As these dopants allow the controlled destabilization of the liposome structure, upon exposure of the doped liposomes to analyte(s) of interest, the indicator color change is facilitated and more easily recognized.

  1. Environment-Responsive Multifunctional Liposomes

    PubMed Central

    Kale, Amit A.; Torchilin, Vladimir P.

    2012-01-01

    Liposomal nanocarriers modified with cell-penetrating peptide and a pH-sensitive PEG shield demonstrate simultaneously a better systemic circulation and site-specific exposure of the cell-penetrating peptide. PEG chains were incorporated into the liposome membrane via the PEG-attached phosphatidylethanolamine (PE) residue with PEG and PE being conjugated with the lowered pH-degradable hydrazone bond (PEG-HZ-PE), while cell-penetrating peptide (TATp) was added as TATp-PEG-PE conjugate. Under normal conditions, liposome-grafted PEG “shielded” liposome-attached TATp moieties, since the PEG spacer for TATp attachment (PEG(1000)) was shorter than protective PEG(2000). PEGylated liposomes accumulate in targets via the EPR effect, but inside the “acidified” tumor or ischemic tissues lose their PEG coating because of the lowered pH-induced hydrolysis of HZ and penetrate inside cells via the now-exposed TATp moieties. pH-responsive behavior of these constructs is successfully tested in cell cultures in vitro as well as in tumors in experimental mice in vivo. These nanocarriers also showed enhanced pGFP transfection efficiency upon intratumoral administration in mice, compared to control pH nonsensitive counterpart. These results can be considered as an important step in the development of tumor-specific stimuli-sensitive drug and gene delivery systems. PMID:20072884

  2. Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation.

    PubMed

    Seidah, Nabil G; Poirier, Steve; Denis, Maxime; Parker, Rex; Miao, Bowman; Mapelli, Claudio; Prat, Annik; Wassef, Hanny; Davignon, Jean; Hajjar, Katherine A; Mayer, Gaétan

    2012-01-01

    Proprotein convertase subtilisin/kexin-9 (PCSK9) enhances the degradation of hepatic low-density lipoprotein receptor (LDLR). Deletion of PCSK9, and loss-of-function mutants in humans result in lower levels of circulating LDL-cholesterol and a strong protection against coronary heart disease. Accordingly, the quest for PCSK9 inhibitors has major clinical implications. We have previously identified annexin A2 (AnxA2) as an endogenous binding partner and functional inhibitor of PCSK9. Herein, we studied the relevance of AnxA2 in PCSK9 inhibition and lipid metabolism in vivo. Plasma analyses of AnxA2(-/-) mice revealed: i) a ∼1.4-fold increase in LDL-cholesterol without significant changes in VLDLs or HDLs, and ii) a ∼2-fold increase in circulating PCSK9 levels. Western blotting and immunohistochemistry of AnxA2(-/-) tissues revealed that the LDLR was decreased by ∼50% in extrahepatic tissues, such as adrenals and colon. We also show that AnxA2-derived synthetic peptides block the PCSK9≡LDLR interaction in vitro, and adenoviral overexpression of AnxA2 in mouse liver increases LDLR protein levels in vivo. These results suggest that AnxA2 acts as an endogenous regulator of LDLR degradation, mostly in extrahepatic tissues. Finally, we identified an AnxA2 coding polymorphism, V98L, that correlates with lower circulating levels of PCSK9 thereby extending our results on the physiological role of AnxA2 in humans.

  3. Biomimetic nanoassemblies of 1-O-octodecyl-2-conjugated linoleoyl-sn-glycero-3-phosphatidyl gemcitabine with phospholipase A2-triggered degradation for the treatment of cancer.

    PubMed

    Zuo, Jing; Tong, Li; Du, Lina; Yang, Ming; Jin, Yiguang

    2017-04-01

    Phospholipids are important biomolecules with strong self-assembling ability to form biomembranes or liposomes. However, biomimetic prodrugs of phospholipids are not well known, including their self-assembling behavior at the air/water interface or in aqueous media. Here we design and prepare a biomimetic phospholipid-like amphiphilic prodrug, 1-O-octodecyl-2-conjugated linoleoyl-sn-glycero-3-phosphatidyl gemcitabine (OLGPG). After spreading at the air/water interface, it formed Langmuir monolayers. Stable nanoassemblies were obtained based on molecular self-assembly after OLGPG was injected in water. An amphiphilic long-chained lipid, cholesteryl hemisuccinate polyethylene glycol 1500 (CHS-PEG) was mixed in the OLGPG Langmuir monolayers and nanoassemblies with the optimal proportion. The OLGPG and OLGPG/CHS-PEG nanoassemblies were spherical vesicles due to the hydrophobic interaction of lipid moieties with the small sizes of 50.33nm and 64.76nm, respectively. Phospholipase A2 (PLA2) is highly expressed in tumor tissues to specifically degrade the 2-acyl of phospholipid to lysophospholipid. OLGPG showed PLA2-sensitive degradation. The nanoassemblies showed higher in vitro anticancer effect on HepG2 cells than the parent drug gemcitabine. In the in vivo studies on the hepatocellular tumor-bearing mouse model, the OLGPG/CHS-PEG nanoassemblies group (eq. to 1/5 dose of the Gem group) showed the highest antitumor and tumor targeting effects compared to the other groups. The long-circulating phospholipid-like prodrug nanoassemblies are the promising anticancer nanomedicines based on the biomimetic strategy and specific tumor microenvironment.

  4. Plasmon resonant liposomes for controlled drug delivery

    NASA Astrophysics Data System (ADS)

    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.

  5. Growth inhibition and microcystin degradation effects of Acinetobacter guillouiae A2 on Microcystis aeruginosa.

    PubMed

    Yi, Yang-Lei; Yu, Xiao-Bo; Zhang, Chao; Wang, Gao-Xue

    2015-01-01

    Strain A2 with algicidal activity against Microcystis aeruginosa was isolated and identified with the genus Acinetobacter on the basis of phenotypic tests and 16S rRNA gene analysis. It was identified with the species Acinetobactor guillouiae by partial rpoB sequence analysis. When 10% (v/v) of the bacterial culture was co-incubated with M. aeruginosa culture, algicidal efficiency reached 91.6% after 7 days. Supernatant of A2 culture showed similar algicidal activity, while the cell pellet had little activity, suggesting that Acinetobacter guillouiae A2 indirectly attacked M. aeruginosa cells by secreting an extracellular algicidal compound, which was characterized as heat-stable. A significant decrease in the microcystin (microcystin-LR) concentration was observed after 10% (v/v) addition of A2 culture. Transcription of three microcystin-related genes (mcyA, mcyD and mcyH) was also found to be inhibited. The algicidal compound 4-hydroxyphenethylamine was obtained by further isolation and purification using various chromatographic techniques. The EC50, 3d and EC50, 7d values of 4-hydroxyphenethylamine against M. aeruginosa were 22.5 and 10.3 mgL(-1), respectively. These results indicate that A. guillouiae strain A2 inhibits growth of M. aeruginosa and degrades microcystin production. The identified compound, 4-hydroxyphenethylamine, has potential for development as a new algicidal formulation or product.

  6. Amphotericin B Liposomal Injection

    MedlinePlus

    Amphotericin B liposomal injection is used to treat fungal infections such as cryptococcal meningitis (a fungal infection of the ... infections in people who cannot receive conventional amphotericin B therapy. Amphotericin B liposomal injection is in a ...

  7. Archaebacterial tetraetherlipid liposomes.

    PubMed

    Ozcetin, Aybike; Mutlu, Samet; Bakowsky, Udo

    2010-01-01

    Liposomes are widely investigated for their applicability as drug delivery systems. However, the unstable liposomal constitution is one of the greatest limitations, because the liposomes undergo fast elimination after application to the human body. In the presented study, novel archeal lipids were used to prepare liposomal formulations which were tested for their stability at elevated temperatures, at different pH-values and after heat sterilization.

  8. Liposome technology. Volume I: Preparation of liposomes

    SciTech Connect

    Gregoriadis, G.

    1984-01-01

    These three volumes cover liposome technology in pharmacology and medicine. Contributors emphasize methodology used in their own laboratories, and include a brief introduction, coverage of relevant literature, applications and critical evaluations for the methods they describe. Volume I examine methods for the preparation of liposomes and auxiliary techniques.

  9. Effect of Liposome Characteristics and Dose on the Pharmacokinetics of Liposomes Coated with Poly(amino acid)s

    PubMed Central

    Romberg, Birgit; Oussoren, Christien; Snel, Cor J.; Hennink, Wim E.

    2007-01-01

    Long-circulating liposomes, such as PEG-liposomes, are frequently studied for drug delivery and diagnostic purposes. In our group, poly(amino acid) (PAA)-based coatings for long-circulating liposomes have been developed. These coatings provide liposomes with similar circulation times as compared to PEG-liposomes, but have the advantage of being enzymatically degradable. For PEG-liposomes it has been reported that circulation times are relatively independent of their physicochemical characteristics. In this study, the influence of factors such as PAA grafting density, cholesterol inclusion, surface charge, particle size, and lipid dose on the circulation kinetics of PAA-liposomes was evaluated after intravenous administration in rats. Prolonged circulation kinetics of PAA-liposomes can be maintained upon variation of liposome characteristics and the lipid dose given. However, the use of relatively high amounts of strongly charge-inducing lipids and a too large mean size is to be avoided. In conclusion, PAA-liposomes represent a versatile drug carrier system for a wide variety of applications. PMID:17674159

  10. Liposomes as nanomedical devices

    PubMed Central

    Bozzuto, Giuseppina; Molinari, Agnese

    2015-01-01

    Since their discovery in the 1960s, liposomes have been studied in depth, and they continue to constitute a field of intense research. Liposomes are valued for their biological and technological advantages, and are considered to be the most successful drug-carrier system known to date. Notable progress has been made, and several biomedical applications of liposomes are either in clinical trials, are about to be put on the market, or have already been approved for public use. In this review, we briefly analyze how the efficacy of liposomes depends on the nature of their components and their size, surface charge, and lipidic organization. Moreover, we discuss the influence of the physicochemical properties of liposomes on their interaction with cells, half-life, ability to enter tissues, and final fate in vivo. Finally, we describe some strategies developed to overcome limitations of the “first-generation” liposomes, and liposome-based drugs on the market and in clinical trials. PMID:25678787

  11. Engineering liposomal nanoparticles for targeted gene therapy.

    PubMed

    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.

  12. HtrA2 regulates beta-amyloid precursor protein (APP) metabolism through endoplasmic reticulum-associated degradation.

    PubMed

    Huttunen, Henri J; Guénette, Suzanne Y; Peach, Camilla; Greco, Christopher; Xia, Weiming; Kim, Doo Yeon; Barren, Cory; Tanzi, Rudolph E; Kovacs, Dora M

    2007-09-21

    Alzheimer disease-associated beta-amyloid peptide is generated from its precursor protein APP. By using the yeast two-hybrid assay, here we identified HtrA2/Omi, a stress-responsive chaperone-protease as a protein binding to the N-terminal cysteinerich region of APP. HtrA2 coimmunoprecipitates exclusively with immature APP from cell lysates as well as mouse brain extracts and degrades APP in vitro. A subpopulation of HtrA2 localizes to the cytosolic side of the endoplasmic reticulum (ER) membrane where it contributes to ER-associated degradation of APP together with the proteasome. Inhibition of the proteasome results in accumulation of retrotranslocated forms of APP and increased association of APP with HtrA2 and Derlin-1 in microsomal membranes. In cells lacking HtrA2, APP holoprotein is stabilized and accumulates in the early secretory pathway correlating with elevated levels of APP C-terminal fragments and increased Abeta secretion. Inhibition of ER-associated degradation (either HtrA2 or proteasome) promotes binding of APP to the COPII protein Sec23 suggesting enhanced trafficking of APP out of the ER. Based on these results we suggest a novel function for HtrA2 as a regulator of APP metabolism through ER-associated degradation.

  13. Enhanced Phospholipase A2 Group 3 Expression by Oxidative Stress Decreases the Insulin-Degrading Enzyme

    PubMed Central

    Yui, Daishi; Nishida, Yoichiro; Nishina, Tomoko; Mogushi, Kaoru; Tajiri, Mio; Ishibashi, Satoru; Ajioka, Itsuki; Ishikawa, Kinya; Mizusawa, Hidehiro; Murayama, Shigeo; Yokota, Takanori

    2015-01-01

    Oxidative stress has a ubiquitous role in neurodegenerative diseases and oxidative damage in specific regions of the brain is associated with selective neurodegeneration. We previously reported that Alzheimer disease (AD) model mice showed decreased insulin-degrading enzyme (IDE) levels in the cerebrum and accelerated phenotypic features of AD when crossbred with alpha-tocopherol transfer protein knockout (Ttpa-/-) mice. To further investigate the role of chronic oxidative stress in AD pathophysiology, we performed DNA microarray analysis using young and aged wild-type mice and aged Ttpa-/- mice. Among the genes whose expression changed dramatically was Phospholipase A2 group 3 (Pla2g3); Pla2g3 was identified because of its expression profile of cerebral specific up-regulation by chronic oxidative stress in silico and in aged Ttpa-/- mice. Immunohistochemical studies also demonstrated that human astrocytic Pla2g3 expression was significantly increased in human AD brains compared with control brains. Moreover, transfection of HEK293 cells with human Pla2g3 decreased endogenous IDE expression in a dose-dependent manner. Our findings show a key role of Pla2g3 on the reduction of IDE, and suggest that cerebrum specific increase of Pla2g3 is involved in the initiation and/or progression of AD. PMID:26637123

  14. Liposomes as potential masking agents in sport doping. Part 2: Detection of liposome-entrapped haemoglobin by flow cytofluorimetry.

    PubMed

    Esposito, Simone; Colicchia, Sonia; de la Torre, Xavier; Donati, Francesco; Mazzarino, Monica; Botrè, Francesco

    2017-02-01

    This work presents an analytical procedure for the identification and characterization of liposome-entrapped haemoglobins, based on flow cytofluorimetry. Flow cytofluorimetric detection is carried out following labelling by two distinct fluorescent reagents, an anti-haemoglobin antibody, fluorescein isothiocyanate conjugated, and an anti-poly(ethylene glycol) antibody, streptavidin-phycoerythrin conjugated. This experimental strategy allows the detection of liposome-entrapped haemoglobins in aqueous media, including plasma; the efficacy of the proposed approach has been verified on whole blood samples added with the liposomal formulation (ex-vivo). Additionally, the proposed technique allows the characterization of several key parameters in the study of liposomal haemoglobins, including, for instance (1) the determination of the degree of haemoglobin entrapment by liposomes; (2) the poly(ethylene glycol) insertion efficiency; and (3) the evaluation of liposome-entrapped haemoglobins stability following storage at 4 °C, allowing to follow both the process of haemoglobin loss from liposomes and the liposome degradation. The procedure is proposed for the detection and characterization of liposome-entrapped haemoglobin formulations to control their misuse in sport, but is also suggested for further applications in biological and clinical laboratory investigations. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Liposomal formulations for inhalation.

    PubMed

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

    2013-08-01

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

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

    PubMed

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

    2015-07-01

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

  17. Formulation and stabilization of riboflavin in liposomal preparations.

    PubMed

    Ahmad, Iqbal; Arsalan, Adeel; Ali, Syed Abid; Sheraz, Muhammad Ali; Ahmed, Sofia; Anwar, Zubair; Munir, Iqra; Shah, Muhammad Raza

    2015-12-01

    A study of the formulation of liposomal preparations of riboflavin (RF) with compositional variations in the content of phosphatidylcholine (PC) and their entrapment efficiency (26-42%) have been conducted. Light transmission characteristics of the liposomal preparations have been determined to evaluate their effect on the amount of light passing through the system to initiate a photochemical reaction. Dynamic light scattering (DLS) and atomic force microscopy (AFM) have been used to study the physical characteristics of liposomes. The liposomal preparations of RF have been subjected to photolysis using visible light and the apparent first- order rate constant, kobs, for the degradation of RF have been determined. The values of kobs (1.73-2.29×10(-3)min(-1)) have been found to decrease linearly with an increase in PC concentration in the range of 12.15 to 14.85 mM. Thus, an increase in PC concentration of liposomes leads to an increase in the stability of RF. RF and its main photoproduct, lumichrome (LC), formed in liposomes have been assayed by a two-component spectrometric method at 356 and 445 nm using an irrelevant absorption correction to compensate for the interference of liposomal components. The fluorescence measurements of RF in liposomes indicate excited singlet state quenching and the formation of a charge-transfer complex between RF and PC. It results in electron transfer from PC to RF to cause photoreduction and stabilization of RF. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Protein expression in liposomes.

    PubMed

    Oberholzer, T; Nierhaus, K H; Luisi, P L

    1999-08-02

    Compartmentalization is one of the key steps in the evolution of cellular structures and, so far, only few attempts have been made to model this kind of "compartmentalized chemistry" using liposomes. The present work shows that even such complex reactions as the ribosomal synthesis of polypeptides can be carried out in liposomes. A method is described for incorporating into 1-palmitoyl-2-oleoyl-sn-3-phosphocholine (POPC) liposomes the ribosomal complex together with the other components necessary for protein expression. Synthesis of poly(Phe) in the liposomes is monitored by trichloroacetic acid of the (14)C-labelled products. Control experiments carried out in the absence of one of the ribosomal subunits show by contrast no significant polypeptide expression. This methodology opens up the possibility of using liposomes as minimal cell bioreactors with growing degree of synthetic complexity, which may be relevant for the field of origin of life as well as for biotechnological applications. Copyright 1999 Academic Press.

  19. Fused liposome and acid induced method for liposome fusion

    SciTech Connect

    Huang, L.; Connor, J.

    1988-12-06

    This patent describes a method of fusing liposomes. It comprises: preparing a suspension of liposomes containing at least one lipid which has a tendency to form the inverted hexagonal phase and at least 20 mol percent of palmitoylhomocysteine; and in the absence of externally added divalent cations, proteins or other macromolecules, acidifying the liposome suspension to reduce the pH of the liposomes to below pH 7, such that at least about 20% of the liposomes fuse to one another.

  20. Dodecaborate lipid liposomes as new vehicles for boron delivery system of neutron capture therapy.

    PubMed

    Ueno, Manabu; Ban, Hyun Seung; Nakai, Kei; Inomata, Ryu; Kaneda, Yasufumi; Matsumura, Akira; Nakamura, Hiroyuki

    2010-05-01

    Closo-dodecaborate lipid liposomes were developed as new vehicles for boron delivery system (BDS) of neutron capture therapy. The current approach is unique because the liposome shell itself possesses cytocidal potential in combination with neutron irradiation. The liposomes composed of closo-dodecaborate lipids DSBL and DPBL displayed high cytotoxicity with thermal neutron irradiation. The closo-dodecaborate lipid liposomes were taken up into the cytoplasm by endocytosis without degradation of the liposomes. Boron concentration of 22.7 ppm in tumor was achieved by injection with DSBL-25% PEG liposomes at 20mg B/kg. Promising BNCT effects were observed in the mice injected with DSBL-25% PEG liposomes: the tumor growth was significantly suppressed after thermal neutron irradiation (1.8 x 10(12)neutrons/cm(2)). (c) 2010 Elsevier Ltd. All rights reserved.

  1. Formulation and in vitro characterization of protein-loaded liposomes

    NASA Astrophysics Data System (ADS)

    Kuzimski, Lauren

    Background/Objective: Protein-based drugs are increasingly used to treat a variety of conditions including cancer and cardio-vascular disease. Due to the immune system's innate ability to degrade the foreign particles quickly, protein-based treatments are generally short-lived. To address this limitation, the objective of the study was to: 1) develop protein-loaded liposomes; 2) characterize size, stability, encapsulation efficiency and rate of protein release; and 3) determine intracellular uptake and distribution; and 4) protein structural changes. Method: Liposomes were loaded with a fluorescent-albumin using freeze-thaw (F/T) methodology. Albumin encapsulation and release were quantified by fluorescence spectroscopic techniques. Flow cytometry was used to determine liposome uptake by macrophages. Epifluorescence microscopy was used to determine cellular distribution of liposomes. Stability was determined using dynamic light scattering by measuring liposome size over one month period. Protein structure was determined using circular dichroism (CD). Result: Encapsulation of albumin in liposome was ˜90% and was dependent on F/T rates, with fifteen cycles yielding the highest encapsulation efficacy (p < 0.05). Albumin-loaded liposomes demonstrated consistent size (<300nm). Release of encapsulated albumin in physiological buffer at 25°C was ˜60% in 72 h. Fluorescence imaging suggested an endosomal route of cellular entry for the FITC-albumin liposome with maximum uptake rates in immune cells (30% at 2hour incubation). CD suggested protein structure is minimally impacted by freeze-thaw methodology. Conclusion: Using F/T as a loading method, we were able to successfully achieve a protein-loaded liposome that was under 300nm, had encapsulation of ˜90%. Synthesized liposomes demonstrated a burst release of encapsulate protein (60%) at 72 hours. Cellular trafficking confirmed endosomal uptake, and minimal protein damage was noticed in CD.

  2. Isolation of a 2-picolinic acid-assimilating bacterium and its proposed degradation pathway.

    PubMed

    Zheng, Chunli; Wang, Qiaorui; Ning, Yanli; Fan, Yurui; Feng, Shanshan; He, Chi; Zhang, Tian C; Shen, Zhenxing

    2017-09-06

    Burkholderia sp. ZD1, aerobically utilizes 2-picolinic acid as a source of carbon, nitrogen and energy, was isolated. ZD1 completely degraded 2-picolinic acid when the initial concentrations ranged from 25 to 300mg/L. Specific growth rate (μ) and specific consumption rate (q) increased continually in the concentration range of 25-100mg/L, and then declined. Based on the Haldane model and Andrew's model, μmax and qmax were calculated as 3.9 and 16.5h(-1), respectively. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) was used to determine the main intermediates in the degradation pathway. Moreover, attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) was innovatively used to deduce the ring cleavage mechanism of N-heterocycle of 2-picolinic acid. To our knowledge, this is the first report on not only the utilization of 2-picolinic acid by a Burkholderia sp., but also applying FT-ICR-MS and ATR-FTIR for exploring the biodegradation pathway of organic compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Liposomes in cosmeceutics.

    PubMed

    Rahimpour, Yahya; Hamishehkar, Hamed

    2012-04-01

    Cosmeceuticals are cosmetic products with biologically active ingredients purporting to have medical or drug-like benefits. Some cosmeceuticals can act effectively when reaching their target sites in the deeper layers of the skin. However, the barrier nature of skin causes significant difficulties for compounds to be delivered through. Therefore, scientists are investigating various strategies to overcome these barrier properties. Liposomes have been claimed to improve the topical delivery of compounds. This paper offers a brief overview of current approaches in the research and development of liposomal formulations to improve the performance of cosmeceuticals, from recent literature. This review deals with the potential of liposomes as a skin delivery system for cosmeceuticals, with a focus on the clinical application of liposomes. Liposomes are well-known vesicular cosmetic delivery systems. The topical application of liposomes offers a wide range of advantages including increased moisturization, restoring action, biodegradability, biocompatibility and extended and slow dermal release. Their similar structure to biological membranes allows penetration into the epidermal barrier, compared with other delivery systems. The incorporation of cosmeceuticals using suitable delivery systems is important in the management of cosmetic disorders.

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

    PubMed

    Pourhassan, Houman; Clergeaud, Gael; Hansen, Anders E; Østrem, Ragnhild G; Fliedner, Frederikke P; Melander, Fredrik; Nielsen, Ole L; O'Sullivan, Ciara K; Kjær, Andreas; Andresen, Thomas L

    2017-09-10

    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 and the presence of serum proteins. We found that serum proteins did not affect the lipase activity of the enzyme towards the membranes but instead sequester the lysolipid byproducts consequently inhibiting their detergent-like cytotoxic properties. In vivo therapeutic potential and safety of the liposomes was investigated in nude mice bearing sPLA2-deficient FaDu squamous carcinoma and sPLA2-expressing Colo205 colorectal adenocarcinoma. After intravenous injections, the tumor growth was suppressed for liposomal L-OHP relative to free drug, but only a weak response was observed for both slow- and fast-releasing sPLA2-sensitive formulations compared to non-sensitive liposomes. Also, the mice did not show longer survival. In turn, for the highly sPLA2-sensitive liposomes, multiple high doses caused petechial cutaneous hemorrhages, along with multifocal hepatonecrotic lesions, suggestive of premature activation in skin and liver irrespective of sPLA2-status of the tumor engraft. These results indicate that although liposomal carriers can improve the antitumor efficacy of platinum

  5. Interaction of Colistin and Colistin Methanesulfonate with Liposomes: Colloidal Aspects and Implications for Formulation

    PubMed Central

    WALLACE, STEPHANIE J.; LI, JIAN; NATION, ROGER L.; PRANKERD, RICHARD J.; BOYD, BEN J.

    2012-01-01

    Interaction of colistin and colistin methanesulfonate (CMS) with liposomes has been studied with the view to understanding the limitations to the use of liposomes as a more effective delivery system for pulmonary inhalation of this important class of antibiotic. Thus, in this study, liposomes containing colistin or CMS were prepared and characterized with respect to colloidal behavior and drug encapsulation and release. Association of anionic CMS with liposomes induced negative charge on the particles. However, degradation of the CMS to form cationic colistin over time was directly correlated with charge reversal and particle aggregation. The rate of degradation of CMS was significantly more rapid when associated with the liposome bilayer than when compared with the same concentration in aqueous solution. Colistin liposomes carried positive charge and were stable. Encapsulation efficiency for colistin was approximately 50%, decreasing with increasing concentration of colistin. Colistin was rapidly released from liposomes on dilution. Although the studies indicate limited utility of colistin or CMS liposomes for long duration controlled-release applications, colistin liposomes were highly stable and may present a potential opportunity for coformulation of colistin with a second antibiotic to colocalize the two drugs after pulmonary delivery. PMID:22623044

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

    PubMed Central

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

    2016-01-01

    Gene therapy is a therapeutic approach to deliver genetic material into cells to alter their function in entire organism. One promising form of gene delivery system (DDS) is liposomes. The success of liposome-mediated gene delivery is a multifactorial issue and well-designed liposomal systems might lead to optimized gene transfection particularly in vivo. Liposomal gene delivery systems face different barriers from their site of application to their target, which is inside the cells. These barriers include presystemic obstacles (epithelial barriers), systemic barriers in blood circulation and cellular barriers. Epithelial barriers differ depending on the route of administration. Systemic barriers include enzymatic degradation, binding and opsonisation. Both of these barriers can act as limiting hurdles that genetic material and their vector should overcome before reaching the cells. Finally liposomes should overcome cellular barriers that include cell entrance, endosomal escape and nuclear uptake. These barriers and their impact on liposomal gene delivery will be discussed in this review. PMID:28228799

  7. Liposome-Cross-Linked Hybrid Hydrogels for Glutathione-Triggered Delivery of Multiple Cargo Molecules.

    PubMed

    Liang, Yingkai; Kiick, Kristi L

    2016-02-08

    Novel, liposome-cross-linked hybrid hydrogels cross-linked by the Michael-type addition of thiols with maleimides were prepared via the use of maleimide-functionalized liposome cross-linkers and thiolated polyethylene glycol (PEG) polymers. Gelation of the materials was confirmed by oscillatory rheology experiments. These hybrid hydrogels are rendered degradable upon exposure to thiol-containing molecules such as glutathione (GSH), via the incorporation of selected thioether succinimide cross-links between the PEG polymers and liposome nanoparticles. Dynamic light scattering (DLS) characterization confirmed that intact liposomes were released upon network degradation. Owing to the hierarchical structure of the network, multiple cargo molecules relevant for chemotherapies, namely doxorubicin (DOX) and cytochrome c, were encapsulated and simultaneously released from the hybrid hydrogels, with differential release profiles that were driven by degradation-mediated release and Fickian diffusion, respectively. This work introduces a facile approach for the development of advanced, hybrid drug delivery vehicles that exhibit novel chemical degradation.

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

    PubMed

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

    2013-03-13

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

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

    PubMed Central

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

    2013-01-01

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

  10. Enzymatic action of phospholipase A₂ on liposomal drug delivery systems.

    PubMed

    Hansen, Anders H; Mouritsen, Ole G; Arouri, Ahmad

    2015-08-01

    The overexpression of secretory phospholipase A2 (sPLA2) in tumors has opened new avenues for enzyme-triggered active unloading of liposomal antitumor drug carriers selectively at the target tumor. However, the effects of the liposome composition, drug encapsulation, and tumor microenvironment on the activity of sPLA2 are still not well understood. We carried out a physico-chemical study to characterize the sPLA2-assisted breakdown of liposomes using dye-release assays in the context of drug delivery and under physiologically relevant conditions. The influence of temperature, lipid concentration, enzyme concentration, and drug loading on the hydrolysis of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC, Tm=42°C) liposomes with snake venom sPLA2 was investigated. The sensitivity of human sPLA2 to the liposome composition was checked using binary lipid mixtures of phosphatidylcholine (PC) and phosphatidylglycerol (PG) phospholipids with C14 and C16 acyl chains. Increasing temperature (36-41°C) was found to mainly shorten the enzyme lag-time, whereas the effect on lipid hydrolysis rate was modest. The enzyme lag-time was also found to be inversely dependent on the lipid-to-enzyme ratio. Drug encapsulation can alter the hydrolysis profile of the carrier liposomes. The activity of human sPLA2 was highly sensitive to the phospholipid acyl-chain length and negative surface charge density of the liposomes. We believe our work will prove useful for the optimization of sPLA2-susceptible liposomal formulations as well as will provide a solid ground for predicting the hydrolysis profile of the liposomes in vivo at the target site.

  11. Liposomes: technologies and analytical applications.

    PubMed

    Jesorka, Aldo; Orwar, Owe

    2008-01-01

    Liposomes are structurally and functionally some of the most versatile supramolecular assemblies in existence. Since the beginning of active research on lipid vesicles in 1965, the field has progressed enormously and applications are well established in several areas, such as drug and gene delivery. In the analytical sciences, liposomes serve a dual purpose: Either they are analytes, typically in quality-assessment procedures of liposome preparations, or they are functional components in a variety of new analytical systems. Liposome immunoassays, for example, benefit greatly from the amplification provided by encapsulated markers, and nanotube-interconnected liposome networks have emerged as ultrasmall-scale analytical devices. This review provides information about new developments in some of the most actively researched liposome-related topics.

  12. Liposomes: Technologies and Analytical Applications

    NASA Astrophysics Data System (ADS)

    Jesorka, Aldo; Orwar, Owe

    2008-07-01

    Liposomes are structurally and functionally some of the most versatile supramolecular assemblies in existence. Since the beginning of active research on lipid vesicles in 1965, the field has progressed enormously and applications are well established in several areas, such as drug and gene delivery. In the analytical sciences, liposomes serve a dual purpose: Either they are analytes, typically in quality-assessment procedures of liposome preparations, or they are functional components in a variety of new analytical systems. Liposome immunoassays, for example, benefit greatly from the amplification provided by encapsulated markers, and nanotube-interconnected liposome networks have emerged as ultrasmall-scale analytical devices. This review provides information about new developments in some of the most actively researched liposome-related topics.

  13. Boronated liposome development and evaluation

    SciTech Connect

    Hawthorne, M.F.

    1995-11-01

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

  14. Liposomal adjuvants for human vaccines.

    PubMed

    Alving, Carl R; Beck, Zoltan; Matyas, Gary R; Rao, Mangala

    2016-06-01

    Liposomes are well-known as drug carriers, and are now critical components of two of six types of adjuvants present in licensed vaccines. The liposomal vaccine adjuvant field has long been dynamic and innovative, and research in this area is further examined as new commercial products appear in parallel with new vaccines. In an arena where successful products exist the potential for new types of vaccines with liposomal adjuvants, and alternative liposomal adjuvants that could emerge for new types of vaccines, are discussed. Major areas include: virosomes, constructed from phospholipids and proteins from influenza virus particles; liposomes containing natural and synthetic neutral or anionic phospholipids, cholesterol, natural or synthetic monophosphoryl lipid A, and QS21 saponin; non-phospholipid cationic liposomes; and combinations and mixtures of liposomes and immunostimulating ingredients as adjuvants for experimental vaccines. Liposomes containing monophosphoryl lipid A and QS21 have considerable momentum that will result soon in emergence of prophylactic vaccines to malaria and shingles, and possible novel cancer vaccines. The licensed virosome vaccines to influenza and hepatitis A will be replaced with virosome vaccines to other infectious diseases. Alternative liposomal formulations are likely to emerge for difficult diseases such as tuberculosis or HIV-1 infection.

  15. Lectin-mediated attachment of liposomes to cornea: influence on transcorneal drug flux

    SciTech Connect

    Schaeffer, H.E.; Breitfeller, J.M.; Krohn, D.L.

    1982-10-01

    A method to enhance retention of drug-bearing liposomes at the corneal surface under conditions of tear flow was investigated. Mixed brain gangliosides were incorporated into the membranes of phosphatidyl choline liposomes to provide receptor sites for wheat germ agglutinin, a plant lectin that binds strongly to both human and rabbit corneal epithelium. Ganglioside-containing liposomes showed a 2.5-fold increase in their binding to rabbit cornea in vitro when corneas were pretreated with wheat germ agglutinin (500 micrograms/ml), suggesting that the lectin mediates specific binding of these liposomes to the corneal surface. In addition, under conditions of continuous tear flow (1 ml/hr), ganglioside-containing liposomes with entrapped carbachol significantly enhanced carbachol flux across isolated rabbit corneas pretreated with wheat germ agglutinin 90 min after drug delivery. The data support the potential use of liposomes as a vehicle for topical drug flux enhancement.

  16. Drug Delivery via Cell Membrane Fusion Using Lipopeptide Modified Liposomes

    PubMed Central

    2016-01-01

    Efficient delivery of drugs to living cells is still a major challenge. Currently, most methods rely on the endocytotic pathway resulting in low delivery efficiency due to limited endosomal escape and/or degradation in lysosomes. Here, we report a new method for direct drug delivery into the cytosol of live cells in vitro and invivo utilizing targeted membrane fusion between liposomes and live cells. A pair of complementary coiled-coil lipopeptides was embedded in the lipid bilayer of liposomes and cell membranes respectively, resulting in targeted membrane fusion with concomitant release of liposome encapsulated cargo including fluorescent dyes and the cytotoxic drug doxorubicin. Using a wide spectrum of endocytosis inhibitors and endosome trackers, we demonstrate that the major site of cargo release is at the plasma membrane. This method thus allows for the quick and efficient delivery of drugs and is expected to have many invitro, ex vivo, and invivo applications. PMID:27725960

  17. Mutants of listeriolysin O for enhanced liposomal delivery of macromolecules.

    PubMed

    Walls, Zachary F; Goodell, Stefanie; Andrews, Chasity D; Mathis, Jonathan; Lee, Kyung-Dall

    2013-04-15

    Delivery of macromolecules into the cytosolic space of eukaryotic cells is a pressing challenge in biopharmaceutics. Macromolecules are often encapsulated into liposomes for protection and improved distribution, but the their size often induces endocytosis of the vehicle at the target site, leading to degradation of the cargo. Listeriolysin O is a key virulence factor of Listeria monocytogenes that forms pores in the endosomal membrane, ultimately allowing the bacterium to escape into the cytosol. This function of LLO has been used to improve cytosolic delivery of liposomally encapsulated macromolecules in a number of instances, but its innate toxicity and immunogenicity have prevented it from achieving widespread acceptance. Through site-directed mutagenesis, this study establishes a mutant of LLO (C484S) with enhanced activity, allowing for a reduction in the amount of LLO used for future applications in liposomal drug delivery. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2016-01-01

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

  19. Influence of physicochemical properties and PEG modification of magnetic liposomes on their interaction with intestinal epithelial Caco-2 cells.

    PubMed

    Kono, Yusuke; Jinzai, Hitomi; Kotera, Yota; Fujita, Takuya

    2017-09-30

    The present study aimed to investigate the effect of particle size (100 and 500 nm), surface charge (cationic, neutral and anionic) and polyethylene glycol (PEG) modification of magnetic liposomes on their interaction with the human intestinal epithelial cell line, Caco-2. The cellular associated amount of all the magnetic liposomes was significantly increased by the presence of a magnetic field. The highest association and internalization into Caco-2 cells was observed with magnetic cationic liposomes. Moreover, small magnetic liposomes were more efficiently associated and taken up into the cells, than large ones. In contrast, PEG modification significantly attenuated the enhancing effect of the magnetic field on the cellular association of magnetic liposomes. We also found that magnetic cationic liposomes had the highest retention properties to Caco-2 cells. Moreover, the retention of large magnetic liposomes to the cells was much longer than that of small ones. In addition, magnetic cationic and neutral liposomes had relatively high stability in Caco-2 cells, whereas magnetic anionic liposomes rapidly degraded. These results indicate that the physicochemical properties and PEG modification of magnetic liposomes greatly influences their intestinal epithelial transport.

  20. Liposome dependent delivery of S-adenosyl methionine to cells by liposomes: a potential treatment for liver disease.

    PubMed

    Wagner, Eric J; Krugner-Higby, Lisa; Heath, Timothy D

    2009-02-01

    The present study demonstrates that the nutritional supplement S-adenosyl methionine (SAMe), the primary methyl donor in mammalian cells, is delivered selectively to cells by anionic liposomes, and is, therefore, a liposome dependent drug. Contrary to our expectations, free SAMe chloride was growth inhibitory in cultured cells. The growth inhibitory potency of SAMe chloride in anionic liposomes composed of distearoylphosphatidylglycerol/cholesterol 2:1 was fivefold greater than that of free SAMe. Neutral liposomes composed of distearoylphosphatidylcholine and cholesterol did not increase the potency of the drug. An improved anionic liposome SAMe formulation was produced by use of the 1,4-butanedisulfonate salt (SD4), adding a metal chelator (EDTA), and lowering the buffer pH from pH 7.0 to pH 4.0. This formulation was 15-fold more potent than free SD4, and was active after more than 28 days at 4 degrees C. SAMe and its potential degradation products were screened for toxicity. Formaldehyde was determined to have potency similar to that of free SAMe chloride in CV1-P cells, suggesting that the growth inhibitory effects of SAMe may partly arise from the formation of formaldehyde. The cytotoxic effects of formaldehyde and the less stable forms of SAMe, (SAMe chloride and SAMe tosylate) were decreased in the presence of 3 mM GSH (IC(50) approximately 0.44 mM). The cytotoxic effects of SD4 were not reduced by GSH, suggesting that this more stable form of SAMe is not toxic through the production of formaldehyde. SD4 in anionic DSPG liposomes stimulated murine IL-6 production in RAW 264 cells at concentrations 25- to 30-fold lower than free drug. This increase in potency for IL-6 production was in keeping with the increase in potency observed in our growth inhibition experiments. These results suggest that SD4 in liposomes may be a potential treatment for acute or chronic liver failure.

  1. Liposome: classification, preparation, and applications

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

    Liposomes, sphere-shaped vesicles consisting of one or more phospholipid bilayers, were first described in the mid-60s. Today, they are a very useful reproduction, reagent, and tool in various scientific disciplines, including mathematics and theoretical physics, biophysics, chemistry, colloid science, biochemistry, and biology. Since then, liposomes have made their way to the market. Among several talented new drug delivery systems, liposomes characterize an advanced technology to deliver active molecules to the site of action, and at present, several formulations are in clinical use. Research on liposome technology has progressed from conventional vesicles to `second-generation liposomes', in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modified surfaces have also been developed using several molecules, such as glycolipids or sialic acid. This paper summarizes exclusively scalable techniques and focuses on strengths, respectively, limitations in respect to industrial applicability and regulatory requirements concerning liposomal drug formulations based on FDA and EMEA documents.

  2. Controlling nucleation in giant liposomes.

    PubMed

    Tester, Chantel C; Whittaker, Michael L; Joester, Derk

    2014-05-30

    We introduce giant liposomes to investigate phase transformations in picoliter volumes. Precipitation of calcium carbonate in the confinement of DPPC liposomes leads to dramatic stabilization of amorphous calcium carbonate (ACC). In contrast, amorphous strontium carbonate (ASC) is a transient species, and BaCO3 precipitation leads directly to the formation of crystalline witherite.

  3. Monodisperse Uni- and Multicompartment Liposomes.

    PubMed

    Deng, Nan-Nan; Yelleswarapu, Maaruthy; Huck, Wilhelm T S

    2016-06-22

    Liposomes are self-assembled phospholipid vesicles with great potential in fields ranging from targeted drug delivery to artificial cells. The formation of liposomes using microfluidic techniques has seen considerable progress, but the liposomes formation process itself has not been studied in great detail. As a result, high throughput, high-yielding routes to monodisperse liposomes with multiple compartments have not been demonstrated. Here, we report on a surfactant-assisted microfluidic route to uniform, single bilayer liposomes, ranging from 25 to 190 μm, and with or without multiple inner compartments. The key of our method is the precise control over the developing interfacial energies of complex W/O/W emulsion systems during liposome formation, which is achieved via an additional surfactant in the outer water phase. The liposomes consist of single bilayers, as demonstrated by nanopore formation experiments and confocal fluorescence microscopy, and they can act as compartments for cell-free gene expression. The microfluidic technique can be expanded to create liposomes with a multitude of coupled compartments, opening routes to networks of multistep microreactors.

  4. Liposomal nanotechnology for cancer theranostics.

    PubMed

    Dai, Zhifei; Yue, Xiuli

    2017-03-05

    Liposomes are a type of biomimetic nanoparticles generated from self-assembling concentric lipid bilayer enclosing an aqueous core domain. They have been attractive nanocarriers for the delivery of many drugs (e.g. radiopharmaceuticals, chemotherapeutic agents, porphyrin) and diagnostic agents (e.g. fluorescent dyes, quantum dots, Gadolinium complex and Fe3O4) by encapsulating (or adsorbing) hydrophilic one inside the liposomal aqueous core domain (or on the bilayer membrane surface), and by entrapping hydrophobic one within the liposomal bilayer. Additionally, the liposome surface can be easily conjugated with targeting molecules. Liposomes may accumulate in cancerous tissues not only passively via enhanced permeability and retention (EPR) effect, but also actively by targeting cancer cell or angiogenic marker specifically. The multimodality imaging functionalization of liposomal therapeutic agents makes them highly attracting for individualized monitoring of the in vivo cancer targeting and pharmacokinetics of liposomes loading therapeutic drugs, and predicting therapeutic efficacy in combination with the helpful information from each imaging technique. The present review article will highlight some main advances of cancer theranostic liposomes with a view to activating further research in the nanomedicine community.

  5. Cross-Linkable Liposomes Stabilize a Magnetic Resonance Contrast-Enhancing Polymeric Fastener

    PubMed Central

    2015-01-01

    Liposomes are commonly used to deliver drugs and contrast agents to their target site in a controlled manner. One of the greatest obstacles in the performance of such delivery vehicles is their stability in the presence of serum. Here, we demonstrate a method to stabilize a class of liposomes that load gadolinium, a magnetic resonance (MR) contrast agent, as a model cargo on their surfaces. We hypothesized that the sequential adsorption of a gadolinium-binding chitosan fastener on the liposome surface followed by covalent cross-linking of the lipid bilayer would provide enhanced stability and improved MR signal in the presence of human serum. To investigate this hypothesis, liposomes composed of diyne-containing lipids were assembled and functionalized via chitosan conjugated with a hydrophobic anchor and diethylenetriaminepentaacetic acid (DTPA). This postadsorption cross-linking strategy served to stabilize the thermodynamically favorable association between liposome and polymeric fastener. Furthermore, the chitosan-coated, cross-linked liposomes proved more effective as delivery vehicles of gadolinium than uncross-linked liposomes due to the reduced liposome degradation and chitosan desorption. Overall, this study demonstrates a useful method to stabilize a broad class of particles used for systemic delivery of various molecular payloads. PMID:24635565

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

    PubMed Central

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

    2012-01-01

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

  7. Propulsion of liposomes using bacterial motors.

    PubMed

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

    2013-05-10

    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.

  8. Biological activity of liposomal vanillin.

    PubMed

    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.

  9. Liposome: classification, preparation, and applications

    PubMed Central

    2013-01-01

    Liposomes, sphere-shaped vesicles consisting of one or more phospholipid bilayers, were first described in the mid-60s. Today, they are a very useful reproduction, reagent, and tool in various scientific disciplines, including mathematics and theoretical physics, biophysics, chemistry, colloid science, biochemistry, and biology. Since then, liposomes have made their way to the market. Among several talented new drug delivery systems, liposomes characterize an advanced technology to deliver active molecules to the site of action, and at present, several formulations are in clinical use. Research on liposome technology has progressed from conventional vesicles to ‘second-generation liposomes’, in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modified surfaces have also been developed using several molecules, such as glycolipids or sialic acid. This paper summarizes exclusively scalable techniques and focuses on strengths, respectively, limitations in respect to industrial applicability and regulatory requirements concerning liposomal drug formulations based on FDA and EMEA documents. PMID:23432972

  10. Liposomes in topical photodynamic therapy.

    PubMed

    Dragicevic-Curic, Nina; Fahr, Alfred

    2012-08-01

    Topical photodynamic therapy (PDT) refers to topical application of a photosensitizer onto the site of skin disease which is followed by illumination and results in death of selected cells. The main problem in topical PDT is insufficient penetration of the photosensitizer into the skin, which limits its use to superficial skin lesions. In order to overcome this problem, recent studies tested liposomes as delivery systems for photosensitizers. This paper reviews the use of different types of liposomes for encapsulating photosensitizers for topical PDT. Liposomes should enhance the photosensitizers' penetration into the skin, while decreasing its absorption into systemic circulation. Only few photosensitizers have currently been encapsulated in liposomes for topical PDT: 5-aminolevulinic acid (5-ALA), temoporfin (mTHPC) and methylene blue. Investigated liposomes enhanced the skin penetration of 5-ALA and mTHPC, reduced their systemic absorption and reduced their cytotoxicity compared with free drugs. Their high tissue penetration should enable the treatment of deep and hyperkeratotic skin lesions, which is the main goal of using liposomes. However, liposomes still do not attract enough attention as drug carriers in topical PDT. In vivo studies of their therapeutic effectiveness are needed in order to obtain enough evidence for their potential clinical use as carriers for photosensitizers in topical PDT.

  11. Liposome Technology for Industrial Purposes

    PubMed Central

    Wagner, Andreas; Vorauer-Uhl, Karola

    2011-01-01

    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. PMID:21490754

  12. Surface functionalization of liposomes with proteins and carbohydrates for use in anti-cancer applications

    NASA Astrophysics Data System (ADS)

    Platt, Virginia M.

    Liposomes can be used to exploit the altered biology of cancer thereby increasing delivery of liposome-associated anti-cancer drugs. In this dissertation, I explore methods that utilize the unique cancer expression of the polymeric glycosaminoglycan hyaluronan (HA) and the HA receptor CD44 to target liposomes to tumors, using liposomes functionalized with proteins or oligosaccharides on their surface. To make it easier to prepare protein-functionalized liposomes, a non-covalent protein/liposome association method based upon metal chelation/his 6 interaction was devised and characterized. I evaluated non-covalent attachment of the prodrug converting enzyme yeast cytosine deaminase, the far-red fluorescent protein mKate, two antigens ovalbumin and the membrane proximal region of an HIV GAG and hyaluronidase, a HA-degrading enzyme. In Chapter 2, I describe the synthesis of hyaluronan-oligosaccharide (HA-O) lipid conjugates and their incorporation into liposomes to target CD44-overexpressing cancer cells. HA-O ligands of defined-length, up to 10 monosaccharides, were attached to lipids via various linkers by reductive amination. The HA-lipids were easily incorporated into liposomes but did not mediate binding of liposomes to CD44 overexpressing cells. In Chapter 3, I evaluate the capacity of tris-NTA-Ni-lipids incorporated within a liposome bilayer to associate with his6-tagged proteins. Tris-NTA-lipids of differing structures and avidities were used to associate yeast cytosine deaminase and mKate to the surface of liposomes. Two tris-NTA-lipids and a mono-NTA lipid associated his-tagged proteins to a 1:1 molar ratio in solution. The proteins remained active while associated with the liposome surface. When challenged in vitro with fetal calf serum, tris-NTA-containing liposomes retained his-tagged proteins longer than mono-NTA. However, the tris-NTA/his6 interaction was found to be in a dynamic state; free yeast cytosine deaminase rapidly competed with pre-bound m

  13. Liposome encapsulation of chelating agents

    DOEpatents

    Rahman, Yueh Erh

    1976-01-13

    A method for transferring a chelating agent across a cellular membrane by encapsulating the charged chelating agent within liposomes and carrying the liposome-encapsulated chelating agent to the cellular membrane where the liposomes containing the chelating agent will be taken up by the cells, thereby transferring the chelating agent across the cellular membrane. A chelating agent can be introduced into the interior of a cell of a living organism wherein the liposomes will be decomposed, releasing the chelating agent to the interior of the cell. The released chelating agent will complex intracellularly deposited toxic heavy metals, permitting the more soluble metal complex to transfer across the cellular membrane from the cell and subsequently be removed from the living organism.

  14. Daunorubicin Hydrochloride and Cytarabine Liposome

    Cancer.gov

    This page contains brief information about daunorubicin hydrochloride and cytarabine liposome and a collection of links to more information about the use of this drug, research results, and ongoing clinical trials.

  15. Polymerase chain reaction in liposomes.

    PubMed

    Oberholzer, T; Albrizio, M; Luisi, P L

    1995-10-01

    Compartmentalization of biochemical reactions within a spherically closed bilayer is an important step in the molecular evolution of cells. Liposomes are the most suitable structures to model this kind of chemistry. We have used the polymerase chain reaction (PCR) to demonstrate that complex biochemical reactions such as DNA replication can be carried out inside these compartments. We describe the first example of DNA amplification by the PCR occurring inside liposomes composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), or of a mixture of POPC and phosphatidylserine. We show that these liposomes are stable even under the high temperature conditions used for PCR. Although only a very small fraction of liposomes contains all eight different reagents together, a significant amount of DNA is produced which can be observed by polyacrylamide gel electrophoresis. This work shows that it is possible to carry out complex biochemical reactions within liposomes, which may be germane to the question of the origin of living cells. We have established the parameters and conditions that are critical for carrying out this complex reaction within the liposome compartment.

  16. Phospholipid liposomes functionalized by protein

    NASA Astrophysics Data System (ADS)

    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.

  17. Plasmon resonant gold-coated liposomes for spectrally coded content release

    NASA Astrophysics Data System (ADS)

    Leung, Sarah J.; Troutman, Timothy S.; Romanowski, Marek

    2009-02-01

    We have recently introduced liposome-supported plasmon resonant gold nanoshells (Troutman et al., Adv. Mater. 2008, 20, 2604-2608). These plasmon resonant gold-coated liposomes are degradable into components of a size compatible with renal clearance, potentially enabling their use as multifunctional agents in applications in nanomedicine, including imaging, diagnostics, therapy, and drug delivery. The present research demonstrates that laser illumination at the wavelength matching the plasmon resonance band of a gold-coated liposome leads to the rapid release of encapsulated substances, which can include therapeutic and diagnostic agents. Leakage of encapsulated contents is monitored through the release of self-quenched fluorescein, which provides an increase in fluorescence emission upon release. Moreover, the resonant peak of these gold-coated liposomes is spectrally tunable in the near infrared range by varying the concentration of gold deposited on the surface of liposomes. Varying the plasmon resonant wavelengths of gold-coated liposomes can provide a method for spectrally-coding their light-mediated content release, so that the release event is initiated by the specific wavelength of light used to illuminate the liposomes. The development of spectrally-coded release can find applications in controlled delivery of multiple agents to support complex diagnostic tests and therapeutic interventions.

  18. Enhanced stability and in vitro bioactivity of surfactant-loaded liposomes containing Asiatic Pennywort extract.

    PubMed

    Saesoo, Somsak; Sramala, Issara; Soottitantawat, Apinan; Charinpanitkul, Tawatchai; Ruktanonchai, Uracha Rungsardthong

    2010-01-01

    The objective of this work has been the microencapsulation of Asiatic Pennywort (AP) extract with lecithin from soybean. The effect of various quantities of non-ionic surfactant (Montanov82) on liposomes upon physicochemical characteristics as well as their in vitro bio-activities was investigated. An addition of surfactant resulted in a decrease in particle size and an increase in percentage AP entrapment efficiency of liposomes. The surfactant-loaded liposomes demonstrated higher stability than surfactant-free liposomes where higher percentage AP remaining of liposomes can be achieved depending on surfactant concentration. No significant difference was found on AP release profiles among varied surfactant concentrations, although a presence of surfactant resulted in prolonged AP release rate. Liposomal AP with 20% w/w surfactant or higher demonstrated low cytotoxicity, a stronger anti-oxidation effect and collagen production on dermal fibroblast cells when compared with free AP and surfactant-free liposomes, possibly due to better cell internalization and less AP degradation in cells.

  19. Plasmon resonant gold-coated liposomes for spectrally coded content release.

    PubMed

    Leung, Sarah J; Troutman, Timothy S; Romanowski, Marek

    2009-02-01

    We have recently introduced liposome-supported plasmon resonant gold nanoshells (Troutman et al., Adv. Mater. 2008, 20, 2604-2608). These plasmon resonant gold-coated liposomes are degradable into components of a size compatible with renal clearance, potentially enabling their use as multifunctional agents in applications in nanomedicine, including imaging, diagnostics, therapy, and drug delivery. The present research demonstrates that laser illumination at the wavelength matching the plasmon resonance band of a gold-coated liposome leads to the rapid release of encapsulated substances, which can include therapeutic and diagnostic agents. Leakage of encapsulated contents is monitored through the release of self-quenched fluorescein, which provides an increase in fluorescence emission upon release. Moreover, the resonant peak of these gold-coated liposomes is spectrally tunable in the near infrared range by varying the concentration of gold deposited on the surface of liposomes. Varying the plasmon resonant wavelengths of gold-coated liposomes can provide a method for spectrally-coding their light-mediated content release, so that the release event is initiated by the specific wavelength of light used to illuminate the liposomes. The development of spectrally-coded release can find applications in controlled delivery of multiple agents to support complex diagnostic tests and therapeutic interventions.

  20. Innovative bionanocomposite films of edible proteins containing liposome-encapsulated nisin and halloysite nanoclay.

    PubMed

    Boelter, Juliana Ferreira; Brandelli, Adriano

    2016-09-01

    Films and coatings based on natural polymers have gained increased interest for food packaging applications. In this work, halloysite and phosphatidylcholine liposomes encapsulating nisin were used to develop nanocomposite films of gelatin and casein. Liposomes prepared with either soybean lecithin or Phospholipon(®) showed particle size ranging from 124 to 178nm and high entrapment efficiency (94-100%). Considering their stability, Phospholipon(®) liposomes with 1.0mg/ml nisin were selected for incorporation into nanocomposite films containing 0.5g/l halloysite. The films presented antimicrobial activity against Listeria monocytogenes, Clostridium perfringens and Bacillus cereus. Scanning electron microscopy revealed that the films had a smooth surface, but showed increased roughness with addition of liposomes and halloysite. Casein films were thinner and slightly yellowish, less rigid and very elastic as compared with gelatin films. Thermogravimetric analysis showed a decrease of the degradation temperature for casein films added with liposomes. The glass transition temperature decreased with addition of liposomes and halloysite. Gelatin and casein films containing nisin-loaded liposomes and halloysite represent an interesting alternative for development of active food packaging. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. The potential of pectin as a stabilizer for liposomal drug delivery systems.

    PubMed

    Smistad, Gro; Bøyum, Silje; Alund, Siv Jorunn; Samuelsen, Anne Berit C; Hiorth, Marianne

    2012-10-15

    The aim of the present study was to investigate the potential of different types of pectin as stabilizers for liposomal drug delivery systems. Positively charged liposomes were coated with commercially available and purified low-methoxylated (LM), high-methoxylated (HM) and amidated (AM) pectins. The samples were stored for up to 12 weeks at 4°C, at room temperature and at 35°C. The change in liposomal size and size distribution, zeta potential, pH, leakage of encapsulated carboxyfluorescein (CF), and lipid degradation were studied. All the types of pectin were found to protect the liposomes against aggregation during storage. The pectin coat did not affect the permeability of the liposome membrane. HM and LM pectin seemed to be the most promising types of pectin due to minimal changes in the zeta potentials during storage for these samples and no detectable lipid degradation. It is concluded that pectin may be used for stabilizing liposomal drug delivery systems. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Degradation of newly synthesized polypeptides by ribosome-associated RACK1/c-Jun N-terminal kinase/eukaryotic elongation factor 1A2 complex.

    PubMed

    Gandin, Valentina; Gutierrez, Gustavo J; Brill, Laurence M; Varsano, Tal; Feng, Yongmei; Aza-Blanc, Pedro; Au, Qingyan; McLaughlan, Shannon; Ferreira, Tiago A; Alain, Tommy; Sonenberg, Nahum; Topisirovic, Ivan; Ronai, Ze'ev A

    2013-07-01

    Folding of newly synthesized polypeptides (NSPs) into functional proteins is a highly regulated process. Rigorous quality control ensures that NSPs attain their native fold during or shortly after completion of translation. Nonetheless, signaling pathways that govern the degradation of NSPs in mammals remain elusive. We demonstrate that the stress-induced c-Jun N-terminal kinase (JNK) is recruited to ribosomes by the receptor for activated protein C kinase 1 (RACK1). RACK1 is an integral component of the 40S ribosome and an adaptor for protein kinases. Ribosome-associated JNK phosphorylates the eukaryotic translation elongation factor 1A isoform 2 (eEF1A2) on serines 205 and 358 to promote degradation of NSPs by the proteasome. These findings establish a role for a RACK1/JNK/eEF1A2 complex in the quality control of NSPs in response to stress.

  3. [Preparation and quality evaluation of Iohexol liposomes].

    PubMed

    Zhou, Rongli; Zhu, Xiali; Hung, Guihua; Zhang, Na; Zhang, Bingjie

    2007-08-01

    The liposomes were prepared by reverse-phase evaporation technique. The morphology of the liposomes, the entrapment efficiency and the particle size distribution were evaluated. The CT signals of Iohexol liposomes in rabbits were compared with those of Iohexol injection in rabbits. The entrapment efficiency of Iohexol liposomes was 82.35% +/- 1.82%. The liposmes were spherical or ellipsoidal shape in shape. The mean diameter of the Iohexol liposomes was 207 7 nm. The polydispersity index was 0.355. The Zeta potential was--1.83 mV. The drug was highly entrapped into the liposomes with good reproduction and stability. The in vitro release of Iohexol liposomes was significantly slower than that of Iohexol,and was 98.57% at 24 h. Iohexol liposomes may reduce the dosage, prolong the effective time of the developing agent, and could reduce the side effects of Iohexol on the blood vessels and cerebral nerves.

  4. Preparation and characterization of gemcitabine liposome injections.

    PubMed

    Zhou, Qinmei; Liu, Liucheng; Zhang, Dengshan; Fan, Xingfeng

    2012-10-01

    Gemcitabine liposome injection (stealth liposomes) has facilitated the targeting of gemcitabine for cancer treatment. We systemically review liposome-based drug-delivery systems, which can improve pharmacokinetics, reduce side effects and potentially increase tumor uptake, for pancreatic cancer therapy. A novel liposomal formulation, which allows for higher tumor targeting efficiencies and can be used in current clinical trials to treat this challenging disease, has gained great popularity and attention. In this study, since extrusion technology was used to make sterile preparation of liposomes, the process included aseptic production process and sterile filtration. During the preparation, it has been found that the lipid concentration, emulsification speed and time, the homogenization times and pattern, the lipid solution temperature are all critical parameters for the character of the gemcitabine liposome injection. The particle size method and zeta potential method to characterize a PEGylated liposomal drug formulation of the anti-cancer agent gemcitabine was developed. The methods are specific, precise, reproducible and sensitive, therefore they are suitable for the determination of particle size and zeta potential of gemcitabine liposome injection. Negative staining technology of transmission electron microscopy revealed that gemcitabine liposome injection has a typical morphology, which enables liposomal surfaces could be seen so additional visual information on the stealth liposome can be routinely obtained in a fast and reliable manner. Moreover, the above three methods are simple, fast and would be used for continuous quality control of gemcitabine liposome injection when it moves to cGMP production scale.

  5. [Liposomal amphotericin B].

    PubMed

    Fukasawa, Masatomo

    2005-01-01

    Liposomal amphotericin B (AmBisome) is a DDS (drug delivery system) formulation of amphotericin B (AMPH-B), and has been developed in an attempt to reduce the toxicity of AMPH-B while retaining its therapeutic efficacy. AMPH-B has been the "gold standard" of antifungal therapy over the past four decades. It has a broad spectrum of fungicidal activity against a number of clinically important pathogens including Aspergillus and Candida. The mechanism of action of AMPH-B involves binding to ergosterol, the principal sterol in fungal cell membranes. Binding to ergosterol causes an increase in fungal membrane permeability, electrolyte leakage, and cell death. AMPH-B has affinity for cholesterol in mammalian membranes, which leads to severe side-effects including kidney damage. AmBisome is a unilamellar vesicle composed of AMPH-B and phospholipid. Upon administration, AmBisome remains intact in the blood and distributes to the tissues where fungal infection may occur, and is disrupted after attachment to the outside of fungal cells, resulting in fungal cell death. AmBisome and AMPH-B show similar in vitro and in vivo antifungal activity and clinical efficacy. However, AmBisome has less infusion-related toxicity and nephrotoxicity than AMPH-B.

  6. Omi/HtrA2 promotes cell death by binding and degrading the anti-apoptotic protein ped/pea-15.

    PubMed

    Trencia, Alessandra; Fiory, Francesca; Maitan, Maria Alessandra; Vito, Pasquale; Barbagallo, Alessia Paola Maria; Perfetti, Anna; Miele, Claudia; Ungaro, Paola; Oriente, Francesco; Cilenti, Lucia; Zervos, Antonis S; Formisano, Pietro; Beguinot, Francesco

    2004-11-05

    ped/pea-15 is a ubiquitously expressed 15-kDa protein featuring a broad anti-apoptotic function. In a yeast two-hybrid screen, the pro-apoptotic Omi/HtrA2 mitochondrial serine protease was identified as a specific interactor of the ped/pea-15 death effector domain. Omi/HtrA2 also bound recombinant ped/pea-15 in vitro and co-precipitated with ped/pea-15 in 293 and HeLa cell extracts. In these cells, the binding of Omi/HtrA2 to ped/pea-15 was induced by UVC exposure and followed the mitochondrial release of Omi/HtrA2 into the cytoplasm. Upon UVC exposure, cellular ped/pea-15 protein expression levels decreased. This effect was prevented by the ucf-101 specific inhibitor of the Omi/HtrA2 proteolytic activity, in a dose-dependent fashion. In vitro incubation of ped/pea-15 with Omi/HtrA2 resulted in ped/pea-15 degradation. In intact cells, the inhibitory action of ped/pea-15 on UVC-induced apoptosis progressively declined at increasing Omi/HtrA2 expression. This further effect of Omi/HtrA2 was also inhibited by ucf-101. In addition, ped/pea-15 expression blocked Omi/HtrA2 co-precipitation with the caspase inhibitor protein XIAP and caspase 3 activation. Thus, in part, apoptosis following Omi/HtrA2 mitochondrial release is mediated by reduction in ped/pea-15 cellular levels. The ability of Omi/HtrA2 to relieve XIAP inhibition on caspases is modulated by the relative levels of Omi/HtrA2 and ped/pea-15.

  7. Liposomes for entrapping local anesthetics: a liposome electrokinetic chromatographic study.

    PubMed

    Lokajová, Jana; Laine, Jaana; Puukilainen, Esa; Ritala, Mikko; Holopainen, Juha M; Wiedmer, Susanne K

    2010-05-01

    Bupivacaine is a lipophilic, long-acting, amide class local anesthetic commonly used in clinical practice to provide local anesthesia during surgical procedures. Several cases of accidental overdose with cardiac arrest and death have been reported since bupivacaine was introduced to human use. Recent case reports have suggested that Intralipid (Fresenius Kabi) is an effective therapy for cardiac toxicity from high systemic concentrations of, e.g. bupivacaine, even though the mechanism behind the interaction is not fully clear yet. Our long-term aim is to develop a sensitive, efficient, and non-harmful lipid-based formulation to specifically trap harmful substances in vivo. In this study, the in vitro interaction of local anesthetics (bupivacaine, prilocaine, and lidocaine) with Intralipid or lipid vesicles containing phosphatidylglycerol, phosphatidylcholine, cardiolipin, cholesterol, and N-palmitoyl-D-erythro-sphingosine (ceramide) was determined by liposome electrokinetic chromatography. The interactions were evaluated by calculating the retention factors and distribution constants. Atomic force microscopy measurements were carried out to confirm that the interaction mechanism was solely due to interactions between the analytes and the moving pseudostationary phase and not by interactions with a stationary lipid phase adsorbed to the fused-silica wall. The heterogeneity of the liposomes was also studied by atomic force microscopy. The liposome electrokinetic chromatography results demonstrate that there is higher interaction between the drugs and negatively charged liposome dispersion than with the commercial Intralipid dispersion.

  8. Liposome-like Nanostructures for Drug Delivery

    PubMed Central

    Gao, Weiwei; Hu, Che-Ming J.; Fang, Ronnie H.; Zhang, Liangfang

    2013-01-01

    Liposomes are a class of well-established drug carriers that have found numerous therapeutic applications. The success of liposomes, together with recent advancements in nanotechnology, has motivated the development of various novel liposome-like nanostructures with improved drug delivery performance. These nanostructures can be categorized into five major varieties, namely: (1) polymer-stabilized liposomes, (2) nanoparticle-stabilized liposomes, (3) core-shell lipid-polymer hybrid nanoparticles, (4) natural membrane-derived vesicles, and (5) natural membrane coated nanoparticles. They have received significant attention and have become popular drug delivery platforms. Herein, we discuss the unique strengths of these liposome-like platforms in drug delivery, with a particular emphasis on how liposome-inspired novel designs have led to improved therapeutic efficacy, and review recent progress made by each platform in advancing healthcare. PMID:24392221

  9. Polymerization of actin by positively charged liposomes

    PubMed Central

    1988-01-01

    By cosedimentation, spectrofluorimetry, and electron microscopy, we have established that actin is induced to polymerize at low salt concentrations by positively charged liposomes. This polymerization occurs only at the surface of the liposomes, and thus monomers not in direct contact with the liposome remain monomeric. The integrity of the liposome membrane is necessary to maintain actin in its polymerized state since disruption of the liposome depolymerizes actin. Actin polymerized at the surface of the liposome is organized into two filamentous structures: sheets of parallel filaments in register and a netlike organization. Spectrofluorimetric analysis with the probe N- pyrenyl-iodoacetamide shows that actin is in the F conformation, at least in the environment of the probe. However, actin assembly induced by the liposome is not accompanied by full ATP hydrolysis as observed in vitro upon addition of salts. PMID:3360852

  10. Chapter 17 - Engineering cationic liposome siRNA complexes for in vitro and in vivo delivery.

    PubMed

    Podesta, Jennifer E; Kostarelos, Kostas

    2009-01-01

    RNA interference, the sequence-specific silencing of gene expression by introduction of short interfering RNA (siRNA) is a powerful tool that that the potential to act as a therapeutic agent and the advantage of decreasing toxic effects on normal tissue sometimes seen with conventional treatments i.e. small molecule inhibitors. Naked, unmodified siRNA is poorly taken up by cells and is subject to degradation when exposed to blood proteins during systemic administration. It has also been shown to produce non-specific immune response as well as having the potential to generate 'off-target' effects. Therefore there is a requirement for a delivery system to not only protect the siRNA and facilitate its uptake, but additionally to offer the potential for targeted delivery with an aim of exploiting the high specificity afforded by RNA interference. Cationic liposomes are the most studied, non-viral delivery system used for nucleic acid delivery. As such, the use of cationic liposomes is promising for siRNA for delivery. Furthermore, polyethylene glycol (PEG) can be incorporated into the liposome formulation to create sterically stabilized or 'stealth' liposomes. Addition of PEG can reduce recognition by the reticuloendothelial system (RES) thereby prolonging circulation time. Here we describe a methodology for the complexation of siRNA with cationic liposomes and PEGylated liposomes using two protocols: mixing and encapsulation. Moreover, the different formulations are compared head to head to demonstrate their efficacy for gene silencing.

  11. In vivo Stability of Ester- and Ether-Linked Phospholipid-Containing Liposomes as Measured by Perturbed Angular Correlation Spectroscopy

    NASA Astrophysics Data System (ADS)

    Derksen, Johannes T.; Baldeschwieler, John D.; Scherphof, Gerrit L.

    1988-12-01

    To evaluate liposome formulations for use as intracellular sustained-release drug depots, we have compared the uptake and degradation in rat liver and spleen of liposomes of various compositions, containing as their bulk phospholipid an ether-linked phospholipid or one of several ester-linked phospholipids, by perturbed angular correlation spectroscopy. Multilamellar and small unilamellar vesicles (MLVs and SUVs), composed of egg phosphatidylcholine, sphingomyelin, distearoyl phosphatidylcholine (DSPC), dipalmitoyl phosphatidylcholine (DPPC) or its analog dihexadecylglycerophosphorylcholine (DHPC), and cholesterol plus phosphatidylserine, and containing 111In complexed to nitrilotriacetic acid, were injected intravenously in rats. Recovery of 111In-labeled liposomes in blood, liver, and spleen was assessed at specific time points after injection and the percentage of liposomes still intact in liver and spleen was determined by measurement of the time-integrated angular perturbation factor 111In of the [G22(∞ )] label. We found that MLVs but not SUVs, having DHPC as their bulk phospholipid, showed an increased resistance against lysosomal degradation as compared to other phospholipid-containing liposomes. The use of diacyl phospholipids with a high gel/liquid-crystalline phase-transition temperature, such as DPPC and DSPC, also retarded degradation of MLV, but not of SUV in the dose range tested, while the rate of uptake of these liposomes by the liver was lower.

  12. In vivo stability of ester- and ether-linked phospholipid-containing liposomes as measured by perturbed angular correlation spectroscopy.

    PubMed Central

    Derksen, J T; Baldeschwieler, J D; Scherphof, G L

    1988-01-01

    To evaluate liposome formulations for use as intracellular sustained-release drug depots, we have compared the uptake and degradation in rat liver and spleen of liposomes of various compositions, containing as their bulk phospholipid an ether-linked phospholipid or one of several ester-linked phospholipids, by perturbed angular correlation spectroscopy. Multilamellar and small unilamellar vesicles (MLVs and SUVs), composed of egg phosphatidylcholine, sphingomyelin, distearoyl phosphatidylcholine (DSPC), dipalmitoyl phosphatidylcholine (DPPC) or its analog dihexadecylglycerophosphorylcholine (DHPC), and cholesterol plus phosphatidylserine, and containing 111In complexed to nitrilotriacetic acid, were injected intravenously in rats. Recovery of 111In-labeled liposomes in blood, liver, and spleen was assessed at specific time points after injection and the percentage of liposomes still intact in liver and spleen was determined by measurement of the time-integrated angular perturbation factor [G22(infinity)] of the 111In label. We found that MLVs but not SUVs, having DHPC as their bulk phospholipid, showed an increased resistance against lysosomal degradation as compared to other phospholipid-containing liposomes. The use of diacyl phospholipids with a high gel/liquid-crystalline phase-transition temperature, such as DPPC and DSPC, also retarded degradation of MLV, but not of SUV in the dose range tested, while the rate of uptake of these liposomes by the liver was lower. PMID:3200855

  13. Bio-Inspired Liposomal Thrombomodulin Conjugate through Bio-Orthogonal Chemistry

    PubMed Central

    Zhang, Hailong; Weingart, Jacob; Jiang, Rui; Peng, Jianhao; Wu, Qingyu

    2013-01-01

    We report the synthesis of bio-inspired liposomal thrombomodulin (TM) conjugates by chemoselective and site-specific liposomal conjugation of recombinant TM at C-terminus. TM is an endothelial cell membrane protein that acts as a major cofactor in the protein C anticoagulant pathway. To closely mimic membrane protein structural features of TM, we proposed membrane-mimetic re-expression of recombinant TM onto liposome. A recombinant TM containing the EGF-like 456 domains and an azidohomoalanine at C-terminus was expressed in E. coli.. Conjugation of the recombinant TM onto liposome via Staudinger ligation and copper-free click chemistry were investigated as an optimal platform for exploring membrane protein TM's activity, respectively. The bio-inspired liposomal TM conjugates were confirmed with Western blotting and protein C activation activity. The recombinant TM-liposome conjugates showed a 2-fold higher kcat/Km value for protein C activation than that of the recombinant TM alone, which indicated that the lipid membrane has a beneficiary effect on the recombinant TM's activity. The reported liposomal protein conjugate approach provides a rationale design strategy for both studying membrane protein TM's functions and generating a membrane protein TM-based anticoagulant agent. PMID:23458546

  14. Endocytosis and intracellular traffic of cholesterol-PDMAEMA liposome complexes in human epithelial-like cells.

    PubMed

    Szymanowski, F; Hugo, A A; Alves, P; Simões, P N; Gómez-Zavaglia, A; Pérez, Pablo F

    2017-08-01

    Liposomes are generally used as delivery systems, as they are capable of encapsulating a wide variety of molecules (i.e. plasmids, recombinant proteins, therapeutic drugs). However, liposomal drug delivery have to fulfill different requirements, such as the effective internalization by the target cells and avoidance of the degradative activity of the intracellular compartments. The use of polymer lipid complexes (PLCs), by including different polymers in the liposome formulation, could improve internalization and intracellular release of drugs. The aim of the present work is to study the mechanisms of cellular uptaking and the intracellular trafficking of PLCs formed with cholesterol-poly(2-(dimethylamino)ethyl methacrylate) CHO-PDMAEMA and lecithin (LC CHO-PD). Calcein-loaded liposomes were used to determine cellular uptake and intracellular localization by flow cytometry and confocal microscopy. Incorporation of CHO-PDMAEMA to lecithin liposomes enhanced the internalization capacity of PLCs. Internalization of PLCs by human epithelial-like cells (HEK-293) diminished at 4°C, suggesting uptake by endocytosis. PLCs showed no co-localization with acidic compartments after internalization. Experiments with endocytosis inhibitors and co-localization of liposomes and albumin, suggested the caveolae endocytic pathway as the most probable route for intracellular trafficking of PLCs. In this work, we demonstrated an efficient uptake of LC CHO-PDs by human epithelial-like cells (HEK-293) through the non-degradative caveolae endocytic pathway. The mode of internalization and the intracellular fate of liposomes under study, suggest a promising use of LC CHO-PDs as drug delivery systems. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Capacious and programmable multi-liposomal carriers

    NASA Astrophysics Data System (ADS)

    Yaroslavov, Alexander A.; Sybachin, Andrey V.; Zaborova, Olga V.; Migulin, Vasiliy A.; Samoshin, Vyacheslav V.; Ballauff, Matthias; Kesselman, Ellina; Schmidt, Judith; Talmon, Yeshayahu; Menger, Fredric M.

    2015-01-01

    Spherical polycationic brushes (SPBs) were synthesized by grafting polycationic chains onto 100 nm polystyrene particles. These particles were exposed to unilamellar egg-lecithin (EL) liposomes with a mean diameter of 40 nm that had been rendered anionic via the presence of 10 molar% of phosphatidylserine (PS1-). The liposomes also contained 30 mole% of a morpholinocyclohexanol-based lipid (MOCH) that undergoes a conformational flip when the pH is decreased from 7.0 to 5.0. Mixtures of SPBs and liposomes at pH 7 gave an electrostatically-driven complex possessing, on average, about 40 liposomes for each SPB particle. It was found that the bound liposomes rapidly release much of their contents when the pH is reduced from 7.0 to 5.0 owing mostly to a MOCH conformational change that creates defects in the bilayer membrane. The drop in pH does not, however, induce a separation of the liposomes from the SPBs. Around 50-60% of the liposome contents escape before, it is reasoned, lateral and transmembrane motion of the membrane components heals the defects and prevents further release. Remarkably, the liposomes complexed with SPB release their cargo much faster than the identical but non-complexed liposomes.Spherical polycationic brushes (SPBs) were synthesized by grafting polycationic chains onto 100 nm polystyrene particles. These particles were exposed to unilamellar egg-lecithin (EL) liposomes with a mean diameter of 40 nm that had been rendered anionic via the presence of 10 molar% of phosphatidylserine (PS1-). The liposomes also contained 30 mole% of a morpholinocyclohexanol-based lipid (MOCH) that undergoes a conformational flip when the pH is decreased from 7.0 to 5.0. Mixtures of SPBs and liposomes at pH 7 gave an electrostatically-driven complex possessing, on average, about 40 liposomes for each SPB particle. It was found that the bound liposomes rapidly release much of their contents when the pH is reduced from 7.0 to 5.0 owing mostly to a MOCH conformational

  16. Radionuclide imaging of liposomal drug delivery.

    PubMed

    van der Geest, Tessa; Laverman, Peter; Metselaar, Josbert M; Storm, Gert; Boerman, Otto C

    2016-09-01

    Ever since their discovery, liposomes have been radiolabeled to monitor their fate in vivo. Despite extensive preclinical studies, only a limited number of radiolabeled liposomal formulations have been examined in patients. Since they can play a crucial role in patient management, it is of importance to enable translation of radiolabeled liposomes into the clinic. Liposomes have demonstrated substantial advantages as drug delivery systems and can be efficiently radiolabeled. Potentially, radiolabeled drug-loaded liposomes form an elegant theranostic system, which can be tracked in vivo using single-photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging. In this review, we discuss important aspects of liposomal research with a focus on the use of radiolabeled liposomes and their potential role in drug delivery and monitoring therapeutic effects. Radiolabeled drug-loaded liposomes have been poorly investigated in patients and no radiolabeled liposomes have been approved for use in clinical practice. Evaluation of the risks, pharmacokinetics, pharmacodynamics and toxicity is necessary to meet pharmaceutical and commercial requirements. It remains to be demonstrated whether the results found in animal studies translate to humans before radiolabeled liposomes can be implemented into clinical practice.

  17. Liposomal Indocyanine Green for Enhanced Photothermal Therapy.

    PubMed

    Yoon, Hwan-Jun; Lee, Hye-Seong; Lim, Ji-Young; Park, Ji-Ho

    2017-02-22

    In this study, we engineered liposomal indocyanine green (ICG) to maximize its photothermal effects while maintaining the fluorescence intensity. Various liposomal formulations of ICG were prepared by varying the lipid composition and the molar ratio between total lipid and ICG, and their photothermal characteristics were evaluated under near-infrared irradiation. We showed that the ICG dispersity in the liposomal membrane and its physical interaction with phospholipids were the main factors determining the photothermal conversion efficiency. In phototherapeutic studies, the optimized formulation of liposomal ICG showed greater anticancer effects in a mouse tumor model compared with other liposomal formulations and the free form of ICG. Furthermore, we utilized liposomal ICG to visualize the metastatic lymph node around the primary tumor under fluorescence imaging guidance and ablate the lymph node with the enhanced photothermal effect, indicating the potential for selective treatment of metastatic lymph node.

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

    PubMed

    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.

  19. Analysis of interaction between liposome membranes induced by stress condition: utilization of liposomes immobilized on indium tin oxide electrode.

    PubMed

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

    2009-11-01

    NBD-cholesterol (NBD-Ch)-modified liposome was immobilized on indium tin oxide (ITO) electrode via the covalent binding method. The transfer of NBD-Ch between the immobilized liposomes and the target liposomes was observed by using a fluorescent microscope. The addition of liposome suspension co-incubated with alpha-chymotrypsin or stimuli-responsive polymer to the surface of the above ITO electrode, enhanced the liposome-liposome interaction, resulting in the promotion of NBD-Ch transfer. The apparent transfer rate constant of NBD-Ch was found to be correlated with the index for the liposome-liposome interaction evaluated by an immobilized liposome chromatography. This suggests that the present method using the liposome-immobilized ITO electrode was effective to evaluate the liposome-liposome interaction induced by the protein or the stimuli-responsive polymer under stress conditions.

  20. Pharmacokinetics and therapeutics of sterically stabilized liposomes in mice bearing C-26 colon carcinoma.

    PubMed

    Huang, S K; Mayhew, E; Gilani, S; Lasic, D D; Martin, F J; Papahadjopoulos, D

    1992-12-15

    Three different liposome types were compared for blood clearance and tissue uptake in mice bearing C-26 colon carcinoma growing either s.c. or in liver. Therapeutic experiments were performed with the liposome preparation showing the highest tumor uptake. Liposomes were composed of solid-phase phosphatidylcholine, either distearoyl phosphatidylcholine or hydrogenated soy phosphatidylcholine, and cholesterol at a 2:1 molar ratio. These liposomes were compared with similar but sterically stabilized liposomes (SL) which, in addition, contained either GM1 ganglioside or phosphatidylethanolamine derivatized with poly(ethylene glycol). Pharmacokinetic analysis of drug disposition was based on the areas under the curve for liposome-entrapped 67Ga uptake per gram of tissue up to 96 h following i.v. injection. The highest tissue area under the curve values with both liposome types were obtained in spleen, liver, and tumor. However, the sterically stabilized liposomes gave an area under the curve value 2-3-fold higher in the s.c. tumor and about 2-fold lower in liver and spleen. The therapeutic efficacy of doxorubicin (DOX) and epirubicin (EPI) encapsulated in poly(ethylene glycol)-derivatized phosphatidylethanolamine-containing liposomes was compared with that of free drug at two doses, 6 and 9 (or 10) mg/kg animal weight. Liposomes containing drug were injected either as a single dose, at different times following tumor implantation, or as three weekly doses starting 10 days after implantation. When injected as a single dose, liposome-encapsulated DOX had the maximal effect on tumor growth when injected 6 to 9 days after tumor implantation. When injected as three weekly doses, with treatment starting with a delay of 10 days, tumors which had grown to a size of approximately 0.05-0.1 cm3 regressed in groups of animals treated with either liposome-encapsulated drug (SL-DOX or SL-EPI) but continued to grow unabated in untreated mice and in mice receiving either of the free

  1. Evaluation of Extrusion Technique for Nanosizing Liposomes

    PubMed Central

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

    2016-01-01

    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, reproducible for

  2. Evaluation of Extrusion Technique for Nanosizing Liposomes.

    PubMed

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

    2016-12-21

    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, reproducible for

  3. Pegylated liposomal doxorubicin in ovarian cancer

    PubMed Central

    Green, Andrew E; Rose, Peter G

    2006-01-01

    Pegylated liposomal doxorubicin is a formulation of doxorubicin in which the molecule itself is packaged in a liposome made of various lipids with an outer coating of polyethylene glycol. Liposomal technology is being used in increasing amounts in the therapy of a variety of cancers, including ovarian cancers. This article reviews the mechanistic actions of this formulation, the Phase II and Phase III data that helped define the role of pegylated liposomal doxorubicin in recurrent ovarian cancer, as well as a discussion of some of the side-effects and their management. PMID:17717964

  4. Interactions of liposomes with dental restorative materials.

    PubMed

    Nguyen, Sanko; Adamczak, Malgorzata; Hiorth, Marianne; Smistad, Gro; Kopperud, Hilde Molvig

    2015-12-01

    The in vitro adsorption and retention of liposomes onto four common types of dental restorative materials (conventional and silorane-based resin composites as well as conventional and resin-modified glass ionomer cements (GIC)) have been investigated due to their potential use in the oral cavity. Uncoated liposomes (positively and negatively charged) and pectin (low- and high-methoxylated) coated liposomes were prepared and characterized in terms of particle size and zeta potential. The adsorption of liposomes was performed by immersion, quantified by fluorescence detection, and visualized by fluorescence imaging and atomic force microscopy. Positive liposomes demonstrated the highest adsorption on all four types of materials likely due to their attractive surface charge. They also retained well (minimum 40% after 60 min) on both conventional resin composite and GIC even when exposed to simulated salivary flow. Although an intermediate initial level of adsorption was found for the pectin coated liposomes, at least 70% high methoxylated-pectin coated liposomes still remained on the conventional resin composite after 60 min flow exposure. This indicates significant contribution of hydrophobic interactions in the prolonged binding of liposomes to resin composites. Based on these results, the present paper suggests two new possible applications of liposomes in the preservation of dental restorations.

  5. Tumor targeting using liposomal antineoplastic drugs

    PubMed Central

    Huwyler, Jörg; Drewe, Jürgen; Krähenbühl, Stephan

    2008-01-01

    During the last years, liposomes (microparticulate phospholipid vesicles) have been used with growing success as pharmaceutical carriers for antineoplastic drugs. Fields of application include lipid-based formulations to enhance the solubility of poorly soluble antitumor drugs, 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. PMID:18488413

  6. Liposome adhesion generates traction stress

    NASA Astrophysics Data System (ADS)

    Murrell, Michael P.; Voituriez, Raphaël; Joanny, Jean-François; Nassoy, Pierre; Sykes, Cécile; Gardel, Margaret L.

    2014-02-01

    Mechanical forces generated by cells modulate global shape changes required for essential life processes, such as polarization, division and spreading. Although the contribution of the cytoskeleton to cellular force generation is widely recognized, the role of the membrane is considered to be restricted to passively transmitting forces. Therefore, the mechanisms by which the membrane can directly contribute to cell tension are overlooked and poorly understood. To address this, we directly measure the stresses generated during liposome adhesion. We find that liposome spreading generates large traction stresses on compliant substrates. These stresses can be understood as the equilibration of internal, hydrostatic pressures generated by the enhanced membrane tension built up during adhesion. These results underscore the role of membranes in the generation of mechanical stresses on cellular length scales and that the modulation of hydrostatic pressure due to membrane tension and adhesion can be channelled to perform mechanical work on the environment.

  7. Liposomal formulations of cytotoxic drugs.

    PubMed

    Janknegt, R

    1996-07-01

    Liposomes are microscopic particles of lipid bilayer membrane that enclose aqueous internal compartments. These drug-delivery systems offer a very interesting opportunity for delivering cytotoxic drugs with equal or improved clinical efficacy and reduced toxicity. The most important clinical application of liposomes until now has been the inclusion of amphotericin B. At the same dose level, liposomal amphotericin B is as effective or slightly less effective than the conventional formulation, but much higher dosages, up to 5-7 mg kg-1day-1, can be given with acceptable toxicity. There are three preparations of cytotoxic drugs in an advanced stage of commercial development. Two of these (Doxil and TLD D99) contain doxorubicin and the other (DaunoXome) contains daunorubicin. The cardiac toxicity of the three preparations under clinical evaluation appears to be low in comparison with conventional doxorubicin or daunorubicin. No direct comparisons between the new formulations are available, so it is not yet possible to make any statements concerning their relative efficacy and toxicity. DaunoXome is the only drug that is approved in any country, and is also the best documented. It is too early to make recommendations concerning the place of these drugs in therapy. The marked increase in concentrations at the site of the tumour has yet to lead to increased therapeutic efficacy. These findings need further investigation. The efficacy of liposomal preparations in Kaposi's sarcoma appears to be similar to that of standard therapy and the clinical tolerance is good. Perhaps combination therapy with other cytotoxic agents could result in improved clinical efficacy. Their cost will probably be high in comparison with standard therapies.

  8. Stereochemistry of enzymatic transformations of (+)β- and (-)β-HBCD with LinA2--a HCH-degrading bacterial enzyme of Sphingobium indicum B90A.

    PubMed

    Heeb, Norbert V; Wyss, Simon A; Geueke, Birgit; Fleischmann, Thomas; Kohler, Hans-Peter E; Bernd Schweizer, W; Moor, Heidi; Lienemann, Peter

    2015-03-01

    LinA2, a bacterial enzyme expressed in various Sphingomonadaceae, catalyzes the elimination of HCl from hexachlorocyclohexanes (HCHs) and, as discussed here, the release of HBr from certain hexabromocyclododecanes (HBCDs). Both classes of compounds are persistent organic pollutants now regulated under the Stockholm Convention. LinA2 selectively catalyzes the transformation of β-HBCDs; other stereoisomers like α-, γ-, and δ-HBCDs are not converted. The transformation of (-)β-HBCD is considerably faster than that of its enantiomer. Here, we present the XRD crystal structure of 1E,5S,6S,9R,10S-pentabromocyclododecene (PBCDE) and demonstrate that its enantiomer with the 1E,5R,6R,9S,10R-configuration is the only metabolite formed during LinA2-catalyzed dehydrobromination of (-)β-HBCD. Formation of this product can be rationalized by HBr elimination at C5 and C6. A reasonable enzyme-substrate complex with the catalytic dyad His-73 and Asp-25 approaching the hydrogen at C6 and a cationic pocket of Lys-20, Try-42 and Arg-129 binding the leaving bromine at C5 was found from in silico docking experiments. A second PBCDE of yet unknown configuration was obtained from (+)β-HBCD. We predicted its stereochemistry to be 1E,5S,6S,9S,10R-PBCDE from docking experiments. The enzyme-substrate complex obtained from LinA2 and an activated conformation of (+)β-HBCD allows the HBr elimination at C9 and C10 leading to the predicted product. Both modeled enzyme-substrate complexes are in line with 1,2-diaxial HBr eliminations. In conclusion, LinA2, a bacterial enzyme of the HCH-degrading strain Sphingobium indicum B90A was able to stereoselectively convert β-HBCDs. Configurations of both PBCDE metabolites were predicted by molecular docking experiments and confirmed in one case by XRD data.

  9. Radioprotective effect of transferrin targeted citicoline liposomes.

    PubMed

    Suresh Reddy, Jannapally; Venkateswarlu, Vobalaboina; Koning, Gerben A

    2006-01-01

    The high level of expression of transferrin receptors (Tf-R) on the surface of endothelial cells of the blood-brain-barrier (BBB) had been widely utilized to deliver drugs to the brain. The primary aim of this study was to use transferrin receptor mediated endocytosis as a pathway for the rational development of holo-transferrin coupled liposomes for drug targeting to the brain. Citicoline is a neuroprotective agent used clinically to treat for instance Parkinson disease, stroke, Alzheimer's disease and brain ischemia. Citicoline does not readily cross the BBB because of its strong polar nature. Hence, citicoline was used as a model drug. (Citicoline liposomes have been prepared using dipalmitoylphosphatidylcholine (DPPC) or distearoylphosphatidylcholine (DSPC) by dry lipid film hydration-extrusion method). The effect of the use of liposomes composed of DPPC or DSPC on their citicoline encapsulation efficiency and their stability in vitro were studied. Transferrin was coupled to liposomes by a technique which involves the prevention of scavenging diferric iron atoms of transferrin. The coupling efficiency of transferrin to the liposomes was studied. In vitro evaluation of transferrin-coupled liposomes was performed for their radioprotective effect in radiation treated cell cultures. In this study, OVCAR-3 cells were used as a model cell type over-expressing the Tf-R and human umbilical vein endothelial cells (HUVEC) as BBB endothelial cell model. The average diameter of DPPC and DSPC liposomes were 138 +/- 6.3 and 79.0 +/- 3.2 nm, respectively. The citicoline encapsulation capacity of DPPC and DSPC liposomes was 81.8 +/- 12.8 and 54.9 +/- 0.04 microg/micromol of phospholipid, respectively. Liposomes prepared from DSPC showed relatively better stability than DPPC liposomes at 37 degrees C and in the presence of serum. Hence, DSPC liposomes were used for transferrin coupling and an average of 46-55 molecules of transferrin were present per liposome. Free citicoline

  10. Disposition of aerosolized liposomal amphotericin B.

    PubMed

    Lambros, M P; Bourne, D W; Abbas, S A; Johnson, D L

    1997-09-01

    Amphotericin B (AmB) is an important drug for the treatment of fungal infection, but toxicity limits the lung tissue doses which may be achieved through intravenous administration. Although incorporation of AmB in liposomes reduces these effects and increases the therapeutic index for intravenous administration, targeted delivery to lung tissues via inhaled liposomal AmB aerosol may be a more effective approach. Aerosolization of liposomal amphotericin B targets the lungs, the organs first infested by many fungi. Development of optimal aerosolized liposomal AmB therapies requires a better understanding of the effect that liposome surface charge has on lung clearance kinetics. In this work we evaluated the clearance kinetics and organ distribution of inhaled liposomal AmB in male Balb/C mice. Mice were exposed via nose only to AmB-containing liposomal aerosols having positive, negative, or neutral surface charge characteristics. The formulations were aerosolized using a Collison nebulizer. Groups of animals were euthanized at predetermined times and the lungs and other organs were analyzed for AmB. AmB was not detected in serum and other organs such as kidneys, liver, and brain. The disposition of neutral and positive liposomal amphotericin B in lungs followed biexponential kinetics. The alpha and beta phase half-lives for positive liposomes were 1.3 and 15.1 days, respectively, and 2.3 and 22 days for neutral liposomes. AmB delivered via negative liposomes exhibited monoexponential clearance with a half-life of 4.5 days. These results suggest that toxic side effects in nontarget tissues are minimal and may indicate a potential for long term protection against fungal infections.

  11. Nanoparticle Stabilized Liposomes for Acne Therapy

    NASA Astrophysics Data System (ADS)

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

    PubMed

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

    2013-11-04

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

  13. Polymer-associated liposomes for the oral delivery of grape pomace extract.

    PubMed

    Manconi, Maria; Marongiu, Francesca; Castangia, Ines; Manca, Maria Letizia; Caddeo, Carla; Tuberoso, Carlo Ignazio Giovanni; D'hallewin, Guy; Bacchetta, Gianluigi; Fadda, Anna Maria

    2016-10-01

    The pomaces from red grapes were used as a source of phenolic antioxidants, which are known to have health-promoting effects. Environmentally-friendly extraction strategies were investigated to improve the rate and recovery of an extract with high phenolic content and antioxidant activity, which were evaluated by the Folin-Ciocalteu, DPPH, ABTS(+), CUPRAC and FRAP assays. The extract was incorporated in liposomes, which were stabilized by the addition of a natural polysaccharide, sodium alginate or arabic gum, widely used in pharmaceutical and food industries as thickeners and stabilizers. Results showed that the polymer-associated liposomes were approximately 300nm in size, spherical in shape, and with high entrapment efficiency. The polymers prevented vesicle degradation in the gastric environment, and played a key role in improving liposomes' performances, especially arabic gum. The polymer-associated liposomes were biocompatible and protected Caco-2 cells against oxidative stress. The achieved results suggest a potential application of the polymer-associated liposomes loaded with the grape pomace extract in the nutraceutical field. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Plasmon resonant gold-coated liposomes for spectrally controlled content release

    NASA Astrophysics Data System (ADS)

    Leung, Sarah J.; Bobnick, Michael C.; Romanowski, Marek

    2010-02-01

    We recently demonstrated that liposome-supported plasmon resonant gold nanoshells are degradable into components of a size compatible with renal clearance, potentially enabling their use as multifunctional agents in applications in nanomedicine, including imaging, diagnostics, therapy, and drug delivery (Troutman et al., Adv. Mater. 2008, 20, 2604-2608). When illuminated with laser light at the wavelength matching their plasmon resonance band, gold-coated liposomes rapidly release their encapsulated substances, which can include therapeutic and diagnostic agents. The present research demonstrates that release of encapsulated agents from gold-coated liposomes can be spectrally controlled by varying the location of the plasmon resonance band; this spectral tuning is accomplished by varying the concentration of gold deposited on the surface of liposomes. Furthermore, the amount of laser energy required for release is qualitatively explained using the concept of thermal confinement (Jacques, Appl. Opt. 1993, 32(3), 2447-2454). Overlapping thermal confinement zones can be avoided by minimizing the laser pulse width, resulting in lower energy requirements for liposomal content release and less global heating of the sample. Control of heating is especially important in drug delivery applications, where it enables spatial and spectral control of delivery and prevents thermal damage to tissue.

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

    PubMed Central

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

    2012-01-01

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

  16. Liposome retention in size exclusion chromatography

    PubMed Central

    Ruysschaert, Tristan; Marque, Audrey; Duteyrat, Jean-Luc; Lesieur, Sylviane; Winterhalter, Mathias; Fournier, Didier

    2005-01-01

    Background Size exclusion chromatography is the method of choice for separating free from liposome-encapsulated molecules. However, if the column is not presaturated with lipids this type of chromatography causes a significant loss of lipid material. To date, the mechanism of lipid retention is poorly understood. It has been speculated that lipid binds to the column material or the entire liposome is entrapped inside the void. Results Here we show that intact liposomes and their contents are retained in the exclusion gel. Retention depends on the pore size, the smaller the pores, the higher the retention. Retained liposomes are not tightly fixed to the beads and are slowly released from the gels upon direct or inverted eluent flow, long washing steps or column repacking. Further addition of free liposomes leads to the elution of part of the gel-trapped liposomes, showing that the retention is transitory. Trapping reversibility should be related to a mechanism of partitioning of the liposomes between the stationary phase, water-swelled polymeric gel, and the mobile aqueous phase. Conclusion Retention of liposomes by size exclusion gels is a dynamic and reversible process, which should be accounted for to control lipid loss and sample contamination during chromatography. PMID:15885140

  17. The protein corona of circulating PEGylated liposomes.

    PubMed

    Palchetti, Sara; Colapicchioni, Valentina; Digiacomo, Luca; Caracciolo, Giulio; Pozzi, Daniela; Capriotti, Anna Laura; La Barbera, Giorgia; Laganà, Aldo

    2016-02-01

    Following systemic administration, liposomes are covered by a 'corona' of proteins, and preserving the surface functionality is challenging. Coating the liposome surface with polyethylene glycol (PEG) is the most widely used anti-opsonization strategy, but it cannot fully preclude protein adsorption. To date, protein binding has been studied following in vitro incubation to predict the fate of liposomes in vivo, while dynamic incubation mimicking in vivo conditions remains largely unexplored. The main aim of this investigation was to determine whether shear stress, produced by physiologically relevant dynamic flow, could influence the liposome-protein corona. The corona of circulating PEGylated liposome was thoroughly compared with that formed by incubation in vitro. Systematic comparison in terms of size, surface charge and quantitative composition was made by dynamic light scattering, microelectrophoresis and nano-liquid chromatography tandem mass spectrometry (nanoLC-MS/MS). Size of coronas formed under static vs. dynamic incubation did not appreciably differ from each other. On the other side, the corona of circulating liposomes was more negatively charged than its static counterpart. Of note, the variety of protein species in the corona formed in a dynamic flow was significantly wider. Collectively, these results demonstrated that the corona of circulating PEGylated liposomes can be considerably different from that formed in a static fluid. This seems to be a key factor to predict the biological activity of a liposomal formulation in a physiological environment.

  18. Liposome-Encapsulated Hemoglobin for Emergency Resuscitation.

    DTIC Science & Technology

    1984-10-01

    have infused liposome -encapsulated amphotericin B to treat patients with systemic fungal infections. Their formulation includes 30% dimyristoyl...procedure, including exploring new industrial-scale methodologies for liposome manufacture. In addition we have focused on basic problems of biophysics...circulation persistance of this new formulation , as produced by the Microfluidizer, is obviously necessary. The influence of negatively-charged lipids on

  19. Methods for using redox liposome biosensors

    DOEpatents

    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.

  20. Structure of DNA-liposome complexes

    SciTech Connect

    Lasic, D.D.; Strey, H.; Podgornik, R.; Stuart, M.C.A.; Frederik, P.M.

    1997-01-29

    Despite numerous studies and commericially available liposome kits, however, the structure of DNA-cationic liposome complexes is still not yet well understood. We have investigated the structure of these complexes using high-resolution cryo electron microscopy (EM) and small angle X-ray scattering (SAXS). 14 refs., 3 figs.

  1. Transfer mechanism of temoporfin between liposomal membranes.

    PubMed

    Hefesha, Hossam; Loew, Stephan; Liu, Xiangli; May, Sylvio; Fahr, Alfred

    2011-03-30

    The transfer kinetics of temoporfin, a classic photosensitizer, was analyzed by investigating the influence of total lipid content, temperature, as well as charge, acyl chain length, and saturation of the lipids in donor vesicles using a mini ion exchange column technique. The obtained results are consistent with an apparent first order kinetics in which the transfer proceeds through both liposome collisions and through the aqueous phase. We present a corresponding theoretical model that accounts for the detailed distribution of drug molecules in donor and acceptor liposomes and predicts the transfer rates as a function of drug concentration and number of donor and acceptor liposomes. The experimentally observed transfer rates depended strongly on the temperature and comply with the Arrhenius equation. Thermodynamic calculations indicate the transfer process to be entropically controlled. In terms of the charge of donor liposomes, positively charged liposomes showed transfer rates faster than negatively charged liposomes whereas the maximum amount transferred was almost the same. A more rigid structure of the donor liposomes increases the transfer rate of temoporfin, which is caused by expelling the drug from the membrane interior, as proposed in former work. In summary, our combined theoretical/experimental approach offers a systematic way to study the mechanism of drug release from liposome-based delivery systems. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. Intravesical liposome therapy for interstitial cystitis.

    PubMed

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

    2017-04-01

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

  3. "Smart" liposomal nanocontainers in biology and medicine.

    PubMed

    Tarahovsky, Y S

    2010-07-01

    The perspectives of using liposomes for delivery of drugs to desired parts of the human body have been intensively investigated for more than 30 years. During this time many inventions have been suggested and different kinds of liposomal devices developed, and a number of them have reached the stages of preclinical or clinical trials. The latest techniques can be used to develop biocompatible nano-sized liposomal containers having some abilities of artificial intellect, such as the presence of sensory and responsive units. However, only a few have been clinically approved. Further improvements in this area depend on our knowledge of the interactions of drugs with the lipid bilayer of liposomes. Further studies on liposomal transport through the human body, their targeting of cells requiring therapeutic treatment, and finally, the development of techniques for controlled drug delivery to desired acceptors on cell surfaces or in cytoplasm are still required.

  4. Neuronal chemotaxis by optically manipulated liposomes

    NASA Astrophysics Data System (ADS)

    Pinato, G.; Lien, L. T.; D'Este, E.; Torre, V.; Cojoc, D.

    2011-08-01

    We probe chemotaxis of single neurons, induced by signalling molecules which were optically delivered from liposomes in the neighbourhood of the cells. We implemented an optical tweezers setup combined with a micro-dissection system on an inverted microscope platform. Molecules of Netrin-1 protein were encapsulated into micron-sized liposomes and manipulated to micrometric distances from a specific growth cone of a hippocampal neuron by the IR optical tweezers. The molecules were then released by breaking the liposomes with UV laser pulses. Chemotaxis induced by the delivered molecules was confirmed by the migration of the growth cone toward the liposome position. Since the delivery can be manipulated with high temporal and spatial resolution and the number of molecules released can be controlled quite precisely by tuning the liposome size and the solution concentration, this technique opens new opportunities to investigate the effect of physiological active compounds as Netrin-1 to neuronal signalling and guidance, which represents an important issue in neurobiology.

  5. Pharmacokinetics of temoporfin-loaded liposome formulations: correlation of liposome and temoporfin blood concentration.

    PubMed

    Decker, Christiane; Schubert, Harald; May, Sylvio; Fahr, Alfred

    2013-03-28

    Liposomal formulations of the highly hydrophobic photosensitizer temoporfin were developed in order to overcome solubility-related problems associated with the current therapy scheme. We have incorporated temoporfin into liposomes of varying membrane composition, cholesterol content, and vesicle size. Specifically, two phosphatidyl oligoglycerols were compared to PEG2000-DSPE with respect to the ability to prolong circulation half life of the liposomal carrier. We measured the resulting pharmacokinetic profile of the liposomal carrier and the incorporated temoporfin in a rat model employing a radioactive lipid label and (14)C-temoporfin. The data for the removal of liposomes and temoporfin were analyzed in terms of classical pharmacokinetic theory assuming a two-compartment model. This model, however, does not allow in a straightforward manner to distinguish between temoporfin eliminated together with the liposomal carrier and temoporfin that is first transferred to other blood components (e. g. plasma proteins) before being eliminated from the blood. We therefore additionally analyzed the data based on two separate one-compartment models for the liposomes and temoporfin. The model yields the ratio of the rate constant of temoporfin elimination together with the liposomal carrier and the rate constant of temoporfin elimination following the transfer to e. g. plasma proteins. Our analysis using this model demonstrates that a fraction of temoporfin is released from the liposomes prior to being eliminated from the blood. In case of unmodified liposomes this temoporfin release was observed to increase with decreasing bilayer fluidity, indicating an accelerated temoporfin transfer from gel-phase liposomes to e. g. plasma proteins. Interestingly, liposomes carrying either one of the three investigated surface-modifying agents did not adhere to the tendencies observed for unmodified liposomes. Although surface-modified liposomes exhibited improved pharmacokinetic

  6. Application of Various Types of Liposomes in Drug Delivery Systems

    PubMed Central

    Alavi, Mehran; Karimi, Naser; Safaei, Mohsen

    2017-01-01

    Liposomes, due to their various forms, require further exploration. These structures can deliver both hydrophilic and hydrophobic drugs for cancer, antibacterial, antifungal, immunomodulation, diagnostics, ophtalmica, vaccines, enzymes and genetic elements. Preparation of liposomes results in different properties for these systems. In addition, based on preparation methods, liposomes types can be unilamellar, multilamellar and giant unilamellar; however, there are many factors and difficulties that affect the development of liposome drug delivery structure. In the present review, we discuss some problems that impact drug delivery by liposomes. In addition, we discuss a new generation of liposomes, which is utilized for decreasing the limitation of the conventional liposomes. PMID:28507932

  7. Application of Various Types of Liposomes in Drug Delivery Systems.

    PubMed

    Alavi, Mehran; Karimi, Naser; Safaei, Mohsen

    2017-04-01

    Liposomes, due to their various forms, require further exploration. These structures can deliver both hydrophilic and hydrophobic drugs for cancer, antibacterial, antifungal, immunomodulation, diagnostics, ophtalmica, vaccines, enzymes and genetic elements. Preparation of liposomes results in different properties for these systems. In addition, based on preparation methods, liposomes types can be unilamellar, multilamellar and giant unilamellar; however, there are many factors and difficulties that affect the development of liposome drug delivery structure. In the present review, we discuss some problems that impact drug delivery by liposomes. In addition, we discuss a new generation of liposomes, which is utilized for decreasing the limitation of the conventional liposomes.

  8. Preparation of quercetin and rutin-loaded ceramide liposomes and drug-releasing effect in liposome-in-hydrogel complex system.

    PubMed

    Park, Soo Nam; Lee, Min Hye; Kim, Su Ji; Yu, Eun Ryeong

    2013-06-07

    In this study, we developed a 2-step delivery system to enhance transdermal permeation of quercetin and its glycoside rutin, an antioxidant. Liposome-in-hydrogel complex systems were prepared by incorporating ceramide liposomes, which consist of biocompatible lipid membranes, into cellulose hydrogel. We evaluated the encapsulation efficiency, in vitro release behavior, and skin permeability of formulations that remained stable for over 3 weeks. Rutin had greater encapsulation efficiency and better in vitro release properties than quercetin. However, quercetin demonstrated greater skin permeability than rutin. We also found that liposome-in-hydrogel complex systems (quercetin, 67.42%; rutin 59.82%) improved skin permeability of quercetin and rutin compared to control (phosphate buffer, pH 7.4) (quercetin, 2.48%; rutin, 1.89%) or single systems of hydrogel (quercetin, 31.77%; rutin, 26.35%) or liposome (quercetin, 48.35%; rutin, 37.41%). These results indicate that liposome-in-hydrogel systems can function as potential drug delivery systems to enhance transdermal permeation of the water-insoluble antioxidants quercetin and rutin.

  9. [A liposomal form of diamidine: reduced toxicity].

    PubMed

    Timofeev, B A; Bolotin, I M; Stepanova, L P; Bogdanov, A A; Georgiu, Kh; Malyshev, S N; Petrovskiĭ; Klibanov, A L; Torchilin, V P

    1991-09-01

    The cultures of Nuttalia eque mainly develop in the reticuloendothelial organs and so in treatment of nuttaliosis in horses and the Nuttalia carriers diamidine, an analog of imidocarb or imidozoline, was used encapsulated in liposomes. The liposomes were prepared with a modification of the phase inversion method (the lipids were dissolved in a mixture of freon-11 and chloroform). The content of the organic solvents in the preparation, as evidenced by gas liquid chromatography, was less than 0.2 per cent. The main fraction consisted of particles 1.5 to 2.5 microns in diameter. The tests on animals of various species revealed a significant decrease in the toxicity of diamidine when used encapsulated in liposomes as compared to the use of the free diamidine. The LD50 of the liposome encapsulated diamidine administered intravenously and intramuscularly was for albino mice 52 and 6000 mg/kg, respectively whereas that of the free diamidine was 0.8 and 84 mg/kg, respectively. In a dose of 10 mg/kg administered intramuscularly the free diamidine induced death in 100 per cent of the horses while in a dose of 10 mg/kg the liposome encapsulated diamidine was satisfactorily tolerated by the animals. The liposome encapsulated diamidine had no unfavourable effect on hepatic antitoxic and metabolic functions. One should hope that the low toxicity of the liposome-encapsulated diamidine will provide its higher chemotherapeutic index.

  10. Oral peptide delivery by tetraether lipid liposomes.

    PubMed

    Parmentier, Johannes; Thewes, Bernhard; Gropp, Felix; Fricker, Gert

    2011-08-30

    The aim of this study is to improve of oral peptide delivery by a novel type of liposomes containing tetraether lipids (TELs) derived from archaea bacteria. Liposomes were used for the oral delivery of the somatostatin analogue octreotide. TELs were extracted from Sulfolobus acidocaldarius and subsequently purified to single compounds. Liposomes were prepared by the film method followed by extrusion. Vesicles in size between 130 and 207 nm were obtained as confirmed by photon correlation spectroscopy. The pharmacokinetics of radiolabeled TELs in liposomes was investigated after oral administration to rats. 1.6% of the applied radioactivity in fed and 1.5% in fasted rats was recovered in the blood and inner organs after 2h, while most of the radioactivity remained in the gastro-intestinal tract. After 24h the percentage of radioactivity in inner organs was reduced to 0.6% in fed rats, respectively 1.0% in fasted animals. Several liposomal formulations containing dipalmitoyl phosphatidylcholine (DPPC) and TELs in different ratios were loaded with octreotide and orally administered. Liposomes with 25% TEL could improve the oral bioavailability of octreotide 4.1-fold and one formulation with a cationic TEL derivative 4.6-fold. TEL-liposomes probably act by protecting the peptide in the gastro-intestinal tract.

  11. Unilamellar liposomes with enhanced boron content.

    PubMed

    Li, Tiejun; Hamdi, Julie; Hawthorne, M Frederick

    2006-01-01

    A new type of boron-rich, DSPC-free, unilamellar liposomes was formed using the novel dual-chain, ionic, nido-carborane lipid, K[nido-7-(C16H33OCH2)2CHOCH2-7,8-C2B9H11] (DAC-16), and cholesterol for encapsulation of an aqueous buffer core. Since DSPC was not necessary for the formation of stable DAC-16 liposomes, the boron concentration of these vesicles was increased dramatically to approximately 8.8 wt % in the dry lipid; these liposomes had a high bilayer boron incorporation efficiency of 98%. DSPC-free liposomes exhibited a size distribution pattern of 40-60 nm, which was in the range normally associated with selective tumor uptake. This size distribution was maintained throughout storage at room temperature for several months. Additionally, optimized liposome formulations incorporating DAC-16, DSPC, and cholesterol were identified having stable size distribution patterns after storage for more than two months at a variety of temperatures. Although animal studies indicate that DAC-16 liposomes are toxic, this new ionic nido-carborane lipid allows the formation of liposomes of high boron content for in vitro applications that require the delivery of large amounts of boron.

  12. New generation of liposomal drugs for cancer.

    PubMed

    Minko, Tamara; Pakunlu, Refika I; Wang, Yang; Khandare, Jayant J; Saad, Maha

    2006-11-01

    This review is focused on liposomes as a delivery system for anticancer agents and more specifically on the advantages of using liposomes as drug nanocarrier in cancer chemotherapy. The main advantages of liposomal drugs over the non-encapsulated drugs include: (1) improved pharmacokinetics and drug release, (2) enhanced intracellular penetration, (3) tumor targeting and preventing adverse side effects and (4) ability to include several active ingredients in one complex liposomal drug delivery system (DDS). The review also includes our recent data on advanced liposomal anticancer drug delivery systems. As a conclusion we propose a novel liposomal DDS which includes inhibitors of pump resistance combined in one liposomal drug delivery system with an inhibitor of antiapoptotic cellular defense, an apoptosis inducer (a traditional anticancer drug) and a targeting moiety. The proposed drug delivery system utilizes a novel three tier approach, simultaneously targeting three molecular targets: (1) extracellular receptors or antigen expressed on the surface of plasma membrane of cancer cells in order to direct the whole system specifically to the tumor, preventing adverse side effects on healthy tissues; (2) drug efflux pumps in order to inhibit them and enhance drug retention by cancer cells, increasing intracellular drug accumulation and thereby limiting the need for prescribed high drug doses that cause adverse drug side effects; and (3) intracellular controlling mechanisms of apoptosis in order to suppress cellular antiapoptotic defense.

  13. Preparation of connexin43-integrated giant Liposomes by a baculovirus expression-liposome fusion method.

    PubMed

    Kamiya, Koki; Tsumoto, Kanta; Arakawa, Satoko; Shimizu, Shigeomi; Morita, Ikuo; Yoshimura, Tetsuro; Akiyoshi, Kazunari

    2010-12-01

    Connexin-43 (Cx43) containing giant liposomes (GL) were prepared by a baculovirus expression-liposome fusion method. Recombinant budded viruses expressing Cx43 were prepared and then fused with GLs containing DOPG/DOPC at pH 4.5. Connexon formation on the GL membrane was observed by transmission electron microscope. Hydrophilic fluorescent dye transfers were observed through a Cx43-mediated pathway not only between Sf9 (Spodoptera frugiperda) cells with Cx43 but also from giant Cx43 liposomes to Cx43-expressing U2OS cells (human osteosarcoma cell). The functional connexin-containing liposome is expected to be useful for cellular cytosolic delivery systems. The original orientation and function of Cx43 was maintained after integration into the liposomes. The liposome fusion method will create new opportunities as a tool for analysis of channel membrane proteins.

  14. Helicobacter pylori TlyA agglutinates liposomes and induces fusion and permeabilization of the liposome membranes.

    PubMed

    Lata, Kusum; Chattopadhyay, Kausik

    2014-06-10

    Helicobacter pylori TlyA is a pore-forming hemolysin with potent cytotoxic activity. To explore the potential membrane-damaging activity of H. pylori TlyA, we have studied its interaction with the synthetic liposome vesicles. In our study, H. pylori TlyA shows a prominent ability to associate with the liposome vesicles without displaying an obligatory requirement for any protein receptor on the liposome membranes. Interaction of TlyA triggers agglutination of the liposome vesicles. Such agglutinating activity of TlyA could also be observed with erythrocytes before the induction of its pore-forming hemolytic activity. In addition to its agglutinating activity against liposomes, TlyA also induces fusion and disruption of the liposome membranes. Altogether, our study highlights novel membrane-damaging properties of H. pylori TlyA that have not been documented previously with any other TlyA family protein.

  15. The Role of Cavitation in Liposome Formation

    PubMed Central

    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 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. PMID:17766335

  16. Long-term stability of sterically stabilized liposomes by freezing and freeze-drying: Effects of cryoprotectants on structure.

    PubMed

    Stark, Brigitte; Pabst, Georg; Prassl, Ruth

    2010-11-20

    Liposomes are widely investigated for their use as drug delivery systems, where they have to meet strict stability criteria. Hence, it is of common interest to establish appropriate storage conditions to improve the shelf life of liposomes. In general, long-term stability can be achieved by freezing as well as freeze-drying, and different carbohydrates or polyalcohols, such as mannitol or glycerol are considered as cryoprotective agents to inhibit liposomal fusion or degradation during freezing procedures. Here, we determined the impact of different cryoprotectants on physicochemical parameters of sterically stabilized PEGylated liposomes, which become increasingly important for pharmaceutical applications. We investigated particle stability in terms of size, lamellarity and thickness of the lipid bilayer using photon correlation spectroscopy and small angle X-ray scattering. Besides, we evaluated the impact of cryoprotectants on the thermal lipid phase behavior of either frozen/thawn or lyophilised/rehydrated PEGylated liposome formulations by differential scanning calorimetry. Optimal results for the preservation of the average size of the extruded unilamellar liposomes during freezing were achieved using a mixture of glycerol and carbohydrate concentrations of about 1% (w/v), irrespective of the carbohydrate used. We found no significant changes in the bilayer organisation, and the transition behavior of lipids was almost uneffected by freezing. In case of freeze-drying, similar carbohydrate concentrations as used for freezing were sufficient to maintain the size of PEGylated liposomes after reconstitution of the dried lyophilised cakes, but our small angle X-ray scattering data provide strong evidence that the lyophilisation/rehydration process affects lipid membrane reorganisation on a molecular level such that a swelling of the bilayer might occur. These internal structural changes, which are not detected by standard particle size analysis, might well

  17. Efficacy of liposomal curcumin in a human pancreatic tumor xenograft model: inhibition of tumor growth and angiogenesis.

    PubMed

    Ranjan, Amalendu P; Mukerjee, Anindita; Helson, Lawrence; Gupta, Rohan; Vishwanatha, Jamboor K

    2013-09-01

    Liposome-based drug delivery has been successful in the past decade, with some formulations being Food and Drug Administration (FDA)-approved and others in clinical trials around the world. The major disadvantage associated with curcumin, a potent anticancer agent, is its poor aqueous solubility and hence low systemic bioavailability. However, curcumin can be encapsulated into liposomes to improve systemic bioavailability. We determined the antitumor effects of a liposomal curcumin formulation against human MiaPaCa pancreatic cancer cells both in vitro and in xenograft studies. Histological sections were isolated from murine xenografts and immunohistochemistry was performed. The in vitro (IC50) liposomal curcumin proliferation-inhibiting concentration was 17.5 μM. In xenograft tumors in nude mice, liposomal curcumin at 20 mg/kg i.p. three-times a week for four weeks induced 42% suppression of tumor growth compared to untreated controls. A potent antiangiogenic effect characterized by a reduced number of blood vessels and reduced expression of vascular endothelial growth factor and annexin A2 proteins, as determined by immunohistochemistry was observed in treated tumors. These data clearly establish the efficacy of liposomal curcumin in reducing human pancreatic cancer growth in the examined model. The therapeutic curcumin-based effects, with no limiting side-effects, suggest that liposomal curcumin may be beneficial in patients with pancreatic cancer.

  18. Targeted Magnetic Liposomes Loaded with Doxorubicin.

    PubMed

    Pradhan, Pallab; Banerjee, Rinti; Bahadur, Dhirendra; Koch, Christian; Mykhaylyk, Olga; Plank, Christian

    2017-01-01

    Targeted delivery systems for anticancer drugs are urgently needed to achieve maximum therapeutic efficacy by site-specific accumulation and thereby minimizing adverse effects resulting from systemic distribution of many potent anticancer drugs. We have prepared folate receptor-targeted magnetic liposomes loaded with doxorubicin, which are designed for tumor targeting through a combination of magnetic and biological targeting. Furthermore, these liposomes are designed for hyperthermia-induced drug release to be mediated by an alternating magnetic field and to be traceable by magnetic resonance imaging (MRI). Here, detailed preparation and relevant characterization techniques of targeted magnetic liposomes encapsulating doxorubicin are described.

  19. Liposome-encapsulated actinomycin for cancer chemotherapy

    DOEpatents

    Rahman, Yueh-Erh; Cerny, Elizabeth A.

    1976-01-01

    An improved method is provided for chemotherapy of malignant tumors by injection of antitumor drugs. The antitumor drug is encapsulated within liposomes and the liposomes containing the encapsulated drug are injected into the body. The encapsulated drug penetrates into the tumor cells where the drug is slowly released and induces degeneration and death of the tumor cells, while any toxicity to the host body is reduced. Liposome encapsulation of actinomycin D has been found to be particularly effective in treating cancerous abdominal tumors, while drastically reducing the toxicity of actinomycin D to the host.

  20. Multifunctional gold coated thermo-sensitive liposomes for multimodal imaging and photo-thermal therapy of breast cancer cells

    NASA Astrophysics Data System (ADS)

    Rengan, Aravind Kumar; Jagtap, Madhura; de, Abhijit; Banerjee, Rinti; Srivastava, Rohit

    2013-12-01

    Plasmon resonant gold nanoparticles of various sizes and shapes have been extensively researched for their applications in imaging, drug delivery and photothermal therapy (PTT). However, their ability to degrade after performing the required function is essential for their application in healthcare. When combined with biodegradable liposomes, they appear to have better degradation capabilities. They degrade into smaller particles of around 5 nm that are eligible candidates for renal clearance. Distearoyl phosphatidyl choline : cholesterol (DSPC : CHOL, 8 : 2 wt%) liposomes have been synthesized and coated with gold by in situ reduction of chloro-auric acid. These particles of size 150-200 nm are analyzed for their stability, degradation capacity, model drug-release profile, biocompatibility and photothermal effects on cancer cells. It is observed that when these particles are subjected to low power continuous wave near infra-red (NIR) laser for more than 10 min, they degrade into small gold nanoparticles of size 5 nm. Also, the gold coated liposomes appear to have excellent biocompatibility and high efficiency to kill cancer cells through photothermal transduction. These novel materials are also useful in imaging using specific NIR dyes, thus exhibiting multifunctional properties for theranostics of cancer.Plasmon resonant gold nanoparticles of various sizes and shapes have been extensively researched for their applications in imaging, drug delivery and photothermal therapy (PTT). However, their ability to degrade after performing the required function is essential for their application in healthcare. When combined with biodegradable liposomes, they appear to have better degradation capabilities. They degrade into smaller particles of around 5 nm that are eligible candidates for renal clearance. Distearoyl phosphatidyl choline : cholesterol (DSPC : CHOL, 8 : 2 wt%) liposomes have been synthesized and coated with gold by in situ reduction of chloro-auric acid. These

  1. Are PEGylated liposomes better than conventional liposomes? A special case for vincristine.

    PubMed

    Wang, Xuling; Song, Yanzhi; Su, Yuqing; Tian, Qingjing; Li, Boqun; Quan, Jingjing; Deng, Yihui

    2016-05-01

    Cancer poses a significant threat to human health worldwide, and many therapies have been used for its palliative and curative treatments. Vincristine has been extensively used in chemotherapy. However, there are two major challenges concerning its applications in various tumors: (1) Vincristine's antitumor mechanism is cell-cycle-specific, and the duration of its exposure to tumor cells can significantly affect its antitumor activity and (2) Vincristine is widely bio-distributed and can be rapidly eliminated. One solution to these challenges is the encapsulation of vincristine into liposomes. Vincristine can be loaded into conventional liposomes, but it quickly leak out owing to its high membrane permeability. Numerous approaches have been attempted to overcome this problem. Vincristine has been loaded into PEGylated liposomes to prolong circulation time and improve tumor accumulation. These liposomes indeed prolong circulation time, but the payout characteristic of vincristine is severer, resulting in a compromised outcome rather than a better efficacy compared to conventional sphingomyelin (SM)/cholesterol (Chol) liposomes. In 2012, the USA Food and Drug Administration (FDA) approved SM/Chol liposomal vincristine (Marqibo®) for commercial use. In this review, we mainly focus on the drug's rapid leakage problem and the potentially relevant solutions that can be applied during the development of liposomal vincristine and the reason for conventional liposomal vincristine rather than PEGylated liposomes has access to the market.

  2. Liposomes for targeting of antigens and drugs: immunoadjuvant activity and liposome-mediated depletion of macrophages.

    PubMed

    van Rooijen, Nico

    2008-08-01

    Liposomes have proven their use as a tool in various immunological studies. In our own studies, both their application as antigen carriers and as drug carriers appeared to be useful. Immune responses were elicited against free soluble protein antigens and against the same antigens in a liposome-associated (particulate) form, in order to compare both types of response. Since we were especially interested in the role of splenic macrophages in both types of response, we developed a liposome-mediated macrophage suicide approach, based on the liposome-mediated internalization of the small hydrophilic molecule clodronate in macrophages. This molecule has a very short half life when released in the circulation, but does not easily cross phospholipid bilayers of liposomes or cell membranes. As a consequence, once ingested by a macrophage in a liposome-encapsulated form, it will be accumulated within the cell as soon as the liposomes are digested with the help of its lysosomal phospholipases. At a certain intracellular clodronate concentration, the macrophage is eliminated by apoptosis. Given the fact that neither the liposomal phospholipids chosen nor clodronate are toxic to other (non-phagocytic) cells, this method has proven its efficacy for depletion of macrophage subsets in various organs. In several cases, organ-specific depletion can be obtained by choosing the right administration route for the clodronate liposomes.

  3. The buckling of spherical liposomes.

    PubMed

    Pamplona, D C; Greenwood, J A; Calladine, C R

    2005-12-01

    In the classical "first approximation" theory of thin-shell structures, the constitutive relations for a generic shell element--i.e. the elastic relations between the bending moments and membrane stresses and the corresponding changes in curvature and strain, respectively-are written as if an element of the shell is flat, although in reality it is curved. In this theory it is believed that discrepancies on account of the use of "flat" constitutive relations will be negligible provided the ratio shell-radius/thickness is of sufficiently large order. In the study of drawing of narrow, cylindrical "tethers" from liposomes it has been known for many years that it is necessary to use instead a constitutive law which explicitly describes a curved element in order to make sense of the mechanics; and indeed such tethers are generally of "thick-walled" proportions. In this paper we show that the proper constitutive relations for a curved element must also be used in the study, by means of shell equations, of the buckling of initially spherical thin-walled giant liposomes under exterior pressure: these involve the inclusion of what we call the "Mkappa" terms, which are not present in the standard "first-approximation" theory. We obtain analytical expressions for both the bifurcation buckling pressure and the slope of the post-buckling path, in terms of the dimensions and elastic constants of the lipid bi-layer, and also the initial state of bending moment in the vesicle. We explain physically how the initial bending moment can affect the bifurcation pressure, whereas it cannot in "first-approximation" theory. We use these results to map the conditions under which the vesicle buckles into an oblate, as distinct from a prolate ("rugby-ball") shape. Some of our results were obtained long ago by the use of energy methods; but our aim here has been to identify precisely what is lacking in "first-approximation" theory in relation to liposomes, and so to put the "shell equations

  4. Vaginal Delivery of Benzydamine Hydrochloride through Liposomes Dispersed in Mucoadhesive Gels.

    PubMed

    Tuğcu-Demiröz, Fatmanur

    2017-07-01

    Liposomal vaginal drug delivery systems are important strategy in the treatment of both topical and systemic diseases. The aim of this study was to develop a vaginal delivery system for benzydamine hydrochloride (BNZ) loaded liposomes dispersed into mucoadhesive gels. The delivery system was also designed for a once a day dosage and to obtain controlled release of the BNZ. For this purpose BNZ containing gel formulations using hydroxypropyl methylcellulose (HPMC) K100M and Carbopol(®) 974P, which are composed of polymers that show promising potential as mucoadhesive vaginal delivery systems, were developed. In addition, a BNZ containing liposome formulation was developed for vaginal administration. To improve the vaginal retention time, liposome was incorporated in HPMC K100M and Carbopol(®) 974P gel formulations. This system is called lipogel. The developed BNZ liposomes have a slightly negative zeta potential (-1.50±0.16 mV), a 2.25±0.009 µm particle size and a 34% entrapment efficiency. These gels and lipogels have appropriate pH, viscosity, textural properties and mucoadhesive value for vaginal administration. Lipogels were found to be the best formulations for in vitro diffusion and ex vivo mucoadhesion. The work of mucoadhesion obtained from liposomes was in the range of 0.027±0.045 and 0.030±0.017 mJ/cm(2), while the value obtained from lipogels was between 0.176±0.037 and 0.243±0.53 mJ/cm(2). N1 and N2 lipogel formulations diffused 57 and 67% of BNZ respectively at the end of 24 h. Moreover, a higher mucoadhesion, which increases drug residence time in comparison to liposomes, could improve BNZ efficacy. In conclusion, BNZ mucoadhesive vaginal lipogel formulations can be promising alternatives to traditional dosage forms for vaginal topical therapy.

  5. Liposomes as Advanced Delivery Systems for Nutraceuticals

    PubMed Central

    Shade, Christopher W.

    2016-01-01

    Liposomes are delivery vehicles for transporting substances into the body effectively via facilitating absorption directly in the mouth or by preventing breakdown by stomach acid. Since the 1970s, liposomes have been investigated as potential drug delivery systems because of their biocompatibility and ability to incorporate both hydrophilic and hydrophobic therapeutic agents. Despite early promise, it was decades later, in the late 1990s to the present, that liposome technologies could create successful commercial products. Oral deliveries are recently emerging as availability of quality phospholipids and reliable homogenization and sizing equipment have become routinely available. Nutritional industry use of liposomes will grow rapidly in the next 5–10 y. High-quality products with more complex mixtures of pure compounds and complex botanical mixtures will offer clinicians less-invasive options for dosing and delivery of these actives. PMID:27053934

  6. Liposomes as delivery systems for antineoplastic drugs

    NASA Astrophysics Data System (ADS)

    Medina, Luis Alberto

    2014-11-01

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

  7. [The entrapped efficiency of BSA liposome].

    PubMed

    Hou, Dong-Zhi; Liu, Chang-Ke; Ping, Qi-Neng; Liang, Xiao-Hui

    2007-05-01

    BSA liposomes were prepared with approximately 100 nm mean particle size under rather gentle experiment conditions, and two-colorimetric coomassie brilliant blue protein was employed to measure the free drug in the entrapped efficiency (EE%) determination of BSA liposomes. Gel filtration was used to measure the EE%, and several Sephadex gels were examined by the separation of liposomes and free drug. To determine the free drug, three methods were compared on two-colorimetric UV spectrophotography, Bradford and two-colorimetric coomassie brilliant blue, separately. Two-colorimetric coomassie brilliant blue process increased the accuracy and improved the sensitivity of the assay about 20-fold comparing with the Bradford method. Two-colorimetric coomassie brilliant blue assay appeared to be more sensitive and showed broader dynamic range to measure the free BSA in the EE% determination of BSA liposome.

  8. Liposomal curcumin and its application in cancer.

    PubMed

    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.

  9. Surface fractals in liposome aggregation.

    PubMed

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

    2009-01-01

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

  10. Status of liposomes as MR contrast agents.

    PubMed

    Unger, E C; Shen, D K; Fritz, T A

    1993-01-01

    Recent work on the development of liposomal magnetic resonance (MR) contrast agents has yielded structures with higher overall relaxivity than that of other nanoparticles of similar diameter. Liposomes incorporating membrane-bound complexes of manganase ("memsomes") produce greater hepatic enhancement per micromole of metal ion than either ferrite particles or paramagnetic chelates. Memsomes also hold promise for targeting of sites outside the liver. Work is in progress to take these agents into clinical trials.

  11. Intradermal and follicular delivery of adapalene liposomes.

    PubMed

    Kumar, Vijay; Banga, Ajay K

    2016-01-01

    Adapalene is a widely used topical anti-acne drug; however, it has many side effects. Liposomal drug delivery can play a major role by targeting delivery to pilosebaceous units, reducing side effects and offering better patient compliance. To prepare and evaluate adapalene-encapsulated liposomes for their physiochemical and skin permeation properties. A liposomal formulation of adapalene was prepared by the film hydration method and characterized for shape, size, polydispersity index (PDI), encapsulation efficiency and thermal behavior by techniques such as Zetasizer®, differential scanning calorimetry and transmission electron microscopy. Stability of the liposomes was evaluated for three months at different storage conditions. In vitro skin permeation studies and confocal laser microscopy were performed to evaluate adapalene permeation in pig ear skin and hair follicles. The optimized process and formulation parameters resulted in homogeneous population of liposomes with a diameter of 86.66 ± 3.5 nm in diameter and encapsulation efficiency of 97.01 ± 1.84% w/w. In vitro permeation studies indicated liposomal formulation delivered more drug (6.72 ± 0.83 μg/cm(2)) in hair follicles than gel (3.33 ± 0.26 μg/cm(2)) and drug solution (1.62 ± 0.054 μg/cm(2)). Drug concentration delivered to the skin layers was also enhanced compared to other two formulations. Confocal microscopy images confirmed drug penetration in the hair follicles when delivered using the liposomal formulation. Adapalene was efficiently encapsulated in liposomes and led to enhanced delivery in hair follicles, the desired target site for acne.

  12. Ehrlich tumor inhibition using doxorubicin containing liposomes.

    PubMed

    Elbialy, Nihal Saad; Mady, Mohsen Mahmoud

    2015-04-01

    Ehrlich tumors were grown in female balb mice by subcutaneous injection of Ehrlich ascites carcinoma cells. Mice bearing Ehrlich tumor were injected with saline, DOX in solution or DOX encapsulated within liposomes prepared from DMPC/CHOL/DPPG/PEG-PE (100:100:60:4) in molar ratio. Cytotoxicity assay showed that the IC50 of liposomes containing DOX was greater than that DOX only. Tumor growth inhibition curves in terms of mean tumor size (cm(3)) were presented. All the DOX formulations were effective in preventing tumor growth compared to saline. Treatment with DOX loaded liposomes displayed a pronounced inhibition in tumor growth than treatment with DOX only. Histopathological examination of the entire tumor sections for the various groups revealed marked differences in cellular features accompanied by varying degrees in necrosis percentage ranging from 12% for saline treated mice to 70% for DOX loaded liposome treated mice. The proposed liposomal formulation can efficiently deliver the drug into the tumor cells by endocytosis (or passive diffusion) and lead to a high concentration of DOX in the tumor cells. The study showed that the formulation of liposomal doxorubicin improved the therapeutic index of DOX and had increased anti-tumor activity against Ehrlich tumor models.

  13. Octanol-assisted liposome assembly on chip

    PubMed Central

    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. PMID:26794442

  14. Liposomal Formulation of Amphiphilic Fullerene Antioxidants

    PubMed Central

    Zhou, Zhiguo; Lenk, Robert P.; Dellinger, Anthony; Wilson, Stephen R.; Sadler, Robert; Kepley, Christopher L.

    2010-01-01

    Novel amphiphilic fullerene[70] derivatives that are rationally designed to intercalate in lipid bilayers are reported, as well as its vesicular formulation with surprisingly high loading capacity up to 65% by weight. The amphiphilic C70 bisadduct forms uniform and dimensionally stable liposomes with auxiliary natural phospholipids as demonstrated by buoyant density test, particle size distribution and 31P NMR. The antioxidant property of fullerenes is retained in the bipolarly functionalized C70 derivative, Amphiphilic Liposomal Malonylfullerene[70] (ALM) as well as in its liposomal formulations, as shown by both electron paramagnetic resonance (EPR) studies and in vitro reactive oxygen species (ROS) inhibition experiments. The liposomally formulated ALM efficiently quenched hydroxyl radicals and superoxide radicals. In addition, the fullerene liposome inhibited radical-induced lipid peroxidation and maintained the integrity of the lipid bilayer structure. This new class of liposomally formulated, amphipathic fullerene compounds represents a novel drug delivery system for fullerenes and provides a promising pathway to treat oxidative stress-related diseases. PMID:20839887

  15. Octanol-assisted liposome assembly on chip

    NASA Astrophysics Data System (ADS)

    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.

  16. Octanol-assisted liposome assembly on chip.

    PubMed

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

    2016-01-22

    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 amphotericin B: clinical experience and perspectives.

    PubMed

    Gibbs, Winter J; Drew, Richard H; Perfect, John R

    2005-04-01

    While amphotericin B deoxycholate (Fungizone, Apothecon Pharmaceuticals) has been considered by many to be the gold standard for the treatment for numerous invasive fungal infections for over 45 years, toxicities associated with its use often necessitate treatment modification or discontinuation. Lipid-based formulations, including liposomal amphotericin B (AmBisome, Fujisawa Healthcare, Inc.), were developed to decrease many of these toxicities while retaining broad antifungal spectrum and potency of amphotericin B. In clinical trials, liposomal amphotericin B has demonstrated efficacy comparable to that of amphotericin B deoxycholate while reducing the incidence of treatment-related nephrotoxicity, electrolyte-wasting, and infusion-related reactions. In addition, recent clinical trials have also compared liposomal amphotericin B with other antifungal classes. Acquisition costs of liposomal amphotericin B are substantially higher than those of amphotericin B deoxycholate and other antifungals. While pharmacoeconomic analyses consider outcomes and other treatment-related costs, they have yet to clearly demonstrate the cost-effectiveness of liposomal amphotericin B when compared with amphotericin B deoxycholate or other antifungal agents. This review will focus primarily on recent liposomal amphotericin B experience and attempt to put its use into perspective considering other available antifungal agents.

  18. Improving solubility and chemical stability of natural compounds for medicinal use by incorporation into liposomes.

    PubMed

    Coimbra, Maria; Isacchi, Benedetta; van Bloois, Louis; Torano, Javier Sastre; Ket, Aldo; Wu, Xiaojie; Broere, Femke; Metselaar, Josbert M; Rijcken, Cristianne J F; Storm, Gert; Bilia, Rita; Schiffelers, Raymond M

    2011-09-20

    compound could be stably encapsulated without chemical degradation. Despite the instability of liposome-association of 3-oxo-C(12)-homoserine lactone and resveratrol, intravenous administration of these compounds inhibited tumor growth for approximately 70% in a murine tumor model, showing that simple solubilization can have important therapeutic benefits.

  19. Skin delivery of hydrophilic molecules from liposomes and polysaccharide-coated liposomes.

    PubMed

    Belhaj, Nabila; Arab-Tehrany, Elmira; Loing, Estelle; Bézivin, Carine

    2017-03-07

    Liposomes are commonly used in cosmetic formulations to increase the bioavailability of active ingredients. We have previously shown that polysaccharide coating of liposomes improves their resistance to surfactants and electrolytes. In the current study, we have assessed the impact of coating on the skin penetration enhancer properties of liposomes. The physicochemical properties of coated liposomes (Ionosomes(™) ) were evaluated before and after encapsulation of two different hydrophilic molecules (caffeine and a hexapeptide), and compared to those observed with non-coated liposomes. Moreover, in vitro permeation experiments were performed using Franz(™) -modified diffusion cells, with normal human skin as membranes. Results showed that both coated and non-coated liposomes significantly improved the bioavailability of hydrophilic active molecules in skin, compared to reference solutions. Although liposome coating slightly reduced entrapment efficiency, the delivery of active molecules was not adversely affected by the process. In conclusion, polysaccharide coating of liposomes allows for better protection of their integrity without compromising the skin bioavailability of the active molecules that they convoy. This article is protected by copyright. All rights reserved.

  20. Anticancer activity of all-trans retinoic acid-loaded liposomes on human thyroid carcinoma cells.

    PubMed

    Cristiano, Maria Chiara; Cosco, Donato; Celia, Christian; Tudose, Andra; Mare, Rosario; Paolino, Donatella; Fresta, Massimo

    2017-02-01

    All-trans retinoic acid (ATRA) is an anti-tumor compound, exerting different anti-cancer effects on different types of cancer cells. Unfortunately, retinoids are also characterized by certain side effects following systemic administration, such as the burning of skin and general malaise. The highly variable degree of bioavailability of ATRA plus its tendency to induce its own destruction through metabolic degradation following oral treatment necessitate the development of alternative formulations. The aim of this work is to evaluate the physico-chemical properties of unilamellar, ATRA-containing liposomes and to investigate the cytotoxic activity of this potential nanomedicine on human thyroid carcinoma cells. Liposomes made up of DPPC/Chol/DSPE-mPEG2000 (6:3:1 molar ratio), characterized by a mean diameter of ∼200nm, a polydispersity index of 0.1 and a negative surface charge, were used as ATRA-carriers and their antiproliferative efficacy was investigated in comparison with the free drug on three different human thyroid carcinoma cell lines (PTC-1, B-CPAP, and FRO) through MTT-testing. The liposomes protected the ATRA against photodegradation and increased its antiproliferative properties due to the improvement of its cellular uptake. ATRA-loaded liposomes could be a novel formulation useful for the treatment of anaplastic thyroid carcinoma. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Impedimetric toxicity assay in microfluidics using free and liposome-encapsulated anticancer drugs.

    PubMed

    Caviglia, Claudia; Zór, Kinga; Montini, Lucia; Tilli, Valeria; Canepa, Silvia; Melander, Fredrik; Muhammad, Haseena B; Carminati, Marco; Ferrari, Giorgio; Raiteri, Roberto; Heiskanen, Arto; Andresen, Thomas L; Emnéus, Jenny

    2015-02-17

    In this work, we have developed a microfluidic cytotoxicity assay for a cell culture and detection platform, which enables both fluid handling and electrochemical/optical detection. The cytotoxic effect of anticancer drugs doxorubicin (DOX), oxaliplatin (OX) as well as OX-loaded liposomes, developed for targeted drug delivery, was evaluated using real-time impedance monitoring. The time-dependent effect of DOX on HeLa cells was monitored and found to have a delayed onset of cytotoxicity in microfluidics compared with static culture conditions based on data obtained in our previous study. The result of a fluorescent microscopic annexin V/propidium iodide assay, performed in microfluidics, confirmed the outcome of the real-time impedance assay. In addition, the response of HeLa cells to OX-induced cytotoxicity proved to be slower than toxicity induced by DOX. A difference in the time-dependent cytotoxic response of fibrosarcoma cells (HT1080) to free OX and OX-loaded liposomes was observed and attributed to incomplete degradation of the liposomes, which results in lower drug availability. The matrix metalloproteinase (MMP)-dependent release of OX from OX-loaded liposomes was also confirmed using laryngopharynx carcinoma cells (FaDu). The comparison and the observed differences between the cytotoxic effects under microfluidic and static conditions highlight the importance of comparative studies as basis for implementation of microfluidic cytotoxic assays.

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

    PubMed

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

    2016-01-01

    The aim of this study is to develop and evaluate food-grade liposomal delivery systems for the antifungal compound natamycin. Liposomes made of various soybean lecithins are prepared by solvent injection, leading to small unilamellar vesicles (<130 nm) with controlled polydispersity, able to encapsulate natamycin without significant modification of their size characteristics. Presence of charged phospholipids and reduced content of phosphatidylcholine in the lecithin mixture are found to be beneficial for natamycin encapsulation, indicating electrostatic interactions of the preservative with the polar head of the phospholipids. The chemical instability of natamycin upon storage in these formulations is however significant and proves that uncontrolled leakage out of the liposomes occurs. Efficient prevention of natamycin degradation is obtained by incorporation of sterols (cholesterol, ergosterol) in the lipid mixture and is linked to higher entrapment levels and reduced permeability of the phospholipid membrane provided by the ordering effect of sterols. Comparable action of ergosterol is observed at concentrations 2.5-fold lower than cholesterol and attributed to a preferential interaction of natamycin-ergosterol as well as a higher control of membrane permeability. Fine-tuning of sterol concentration allows preparation of liposomal suspensions presenting modulated in vitro release kinetics rates and enhanced antifungal activity against the model yeast Saccharomyces cerevisiae.

  3. [Assemble of magnetic nanoparticles into the structure of cisplatin liposome].

    PubMed

    Wang, Lu; Yang, Cai-qin; Wang, Jing

    2011-05-01

    Effects of different procedures of magnetic nanoparticles into the liposome structure on the distribution of magnetic particles in the liposome were investigated. Magnetic liposomes with high-encapsulating rate of cisplatin (CDDP) were obtained. Fe3O4 magnetic nanoparticles which was modified by organic functional group on surface was synthesized by an one-step modified hydrothermal method. The CDDP magnetic liposomes were prepared by a film scattering-ultrasonic technique and the concentrations of CDDP in the liposomes were measured by graphite furnace atomic absorbance spectroscopy. Magnetic liposomes with different microstructure were prepared by the two different procedures, where the magnetic particles were combined with phospholipid before the film preparation to form liposome in procedure I, and drug solution and the magnetic particles were mixed before hydrating the lipids film to form liposome in procedure II. The liposome structure was observed by transmission electron microscope (TEM). The CDDP magnetic liposomes were prepared by the optimized method which was selected by orthogonal test. Encapsulation rate of the magnetic particles distributed in the phospholipid bilayer through the procedure I was 34.90%. While liposome, produced by the procedure II technique, contained magnetic particles in the interior aqueous compartment, which encapsulation rate was 28.34%. Encapsulation rates of both I and II were higher than that of conventional liposome. The release profile of all the three different liposomes in vitro fitted with a first-order equation. Because of distribution of magnetic particles in the phospholipid bilayer, the skeleton of phospholipid bilayer was changed. The releasing tl/2 of magnetic liposomes produced by the procedure I technique is 9 h, which is shorter than that of the other two liposomes. Assemble of magnetic nanoparticles into the structure of liposome was succeeded by the procedure I, which showed superiority than by procedure II

  4. Entrapment of nucleic acids in liposomes.

    PubMed

    Monnard, P A; Oberholzer, T; Luisi, P

    1997-10-02

    The entrapment efficiency of three main methods used in the literature for the encapsulation of nucleic acids in liposomes were studied using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) liposomes. In particular the reverse phase method, the dehydration/rehydration method, and the freeze/thawing method were compared to each other under standardised conditions, i.e. using in every case the same concentration of guest molecules (DNA, tRNA and ATP as low molecular weight analogue) and equally extruded liposomes. The percentage of entrapment strictly referred to the material localized inside the liposomes, i.e. particular care was devoted to ruling out the contribution of the nucleic acid material bound to the outer surface of the liposomes: this was eliminated by extensive enzymatic digestion prior to column chromatography. Depending on the conditions used, the percentage of the entrapped material varied between 10 and 54% of the initial amount. Further, the encapsulation efficiency was markedly affected by the salt concentration, by the size of liposomes, but to a lower degree by the molecular weight of the guest molecules. In general, we observed that the freeze/thawing encapsulation procedure was the most efficient one. In a second part of the work the freeze/thawing method was applied to encapsulate DNA (369 bp and 3368 bp, respectively) using liposomes obtained from POPC mixed with 1-10% charged cosurfactant, i.e. phosphatidylserine (PS) or didodecyldimethylammonium bromide (DDAB), respectively. Whereas PS had no significant effect, the entrapment efficiency went up to 60% in POPC/DDAB (97.5:2.5) liposomes. The large entrapment efficiency of DNA permits spectroscopic investigations of the DNA encapsulated in the water pool of the liposomes. UV absorption and circular dichroism spectra were practically the same as in water, indicating no appreciable perturbation of the electronic transitions or of the conformation of the entrapped biopolymer. This was

  5. New drug candidates for liposomal delivery identified by computer modeling of liposomes' remote loading and leakage.

    PubMed

    Cern, Ahuva; Marcus, David; Tropsha, Alexander; Barenholz, Yechezkel; Goldblum, Amiram

    2017-02-16

    Remote drug loading into nano-liposomes is in most cases the best method for achieving high concentrations of active pharmaceutical ingredients (API) per nano-liposome that enable therapeutically viable API-loaded nano-liposomes, referred to as nano-drugs. This approach also enables controlled drug release. Recently, we constructed computational models to identify APIs that can achieve the desired high concentrations in nano-liposomes by remote loading. While those previous models included a broad spectrum of experimental conditions and dealt only with loading, here we reduced the scope to the molecular characteristics alone. We model and predict API suitability for nano-liposomal delivery by fixing the main experimental conditions: liposome lipid composition and size to be similar to those of Doxil® liposomes. On that basis, we add a prediction of drug leakage from the nano-liposomes during storage. The latter is critical for having pharmaceutically viable nano-drugs. The "load and leak" models were used to screen two large molecular databases in search of candidate APIs for delivery by nano-liposomes. The distribution of positive instances in both loading and leakage models was similar in the two databases screened. The screening process identified 667 molecules that were positives by both loading and leakage models (i.e., both high-loading and stable). Among them, 318 molecules received a high score in both properties and of these, 67 are FDA-approved drugs. This group of molecules, having diverse pharmacological activities, may be the basis for future liposomal drug development.

  6. Temoporfin-loaded liposomes: physicochemical characterization.

    PubMed

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

    2010-07-11

    Temoporfin (mTHPC) is a potent but highly hydrophobic second-generation photosensitizer and has been approved for the palliative treatment of patients with advanced head and neck cancer by photodynamic therapy. Liposome formulations have been evaluated as carrier system for this drug to overcome some problems associated with the commercial formulation Foscan where the drug is dissolved in a mixture of water-free ethanol and propylene glycol. The present study focuses on the physicochemical characterization of different liposome formulations with special emphasis on the influence of drug incorporation on the thermal phase behavior of the liposomes. In addition to conventional liposomes, pegylated lipids were used for the preparation of "stealth" liposomes. The dispersions as well as freeze-dried formulations were characterized by photon correlation spectroscopy, differential scanning calorimetry and cryo-electron microscopy. Incorporation of temoporfin resulted in a distinct concentration dependent decrease of the main phase transition of the liposomes. In case of liposomes based on dipalmitoylphosphatidylcholine/-glycerol, phase transition was close or even below body temperature. In contrast, if phospholipids with longer fatty acid chains (distearoylphosphatidylcholine/-glycerol) were used, phase transitions were well above body temperature even at high drug load. Size and thermal behavior were not distinctly influenced by the addition of pegylated lipids but cryo-electron microscopic investigations indicate the presence of micellar structures in addition to vesicles. Lyophilization and reconstitution led to an alteration in the morphology but had overall no distinct influence on the colloidal stability. 2010 Elsevier B.V. All rights reserved.

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

    PubMed Central

    Mufamadi, Maluta S.; Pillay, Viness; Choonara, Yahya E.; Du Toit, Lisa C.; Modi, Girish; Naidoo, Dinesh; Ndesendo, Valence M. K.

    2011-01-01

    The combination of liposomes with polymeric scaffolds could revolutionize the current state of drug delivery technology. Although liposomes have been extensively studied as a promising drug delivery model for bioactive compounds, there still remain major drawbacks for widespread pharmaceutical application. Two approaches for overcoming the factors related to the suboptimal efficacy of liposomes in drug delivery have been suggested. The first entails modifying the liposome surface with functional moieties, while the second involves integration of pre-encapsulated drug-loaded liposomes within depot polymeric scaffolds. This attempts to provide ingenious solutions to the limitations of conventional liposomes such as short plasma half-lives, toxicity, stability, and poor control of drug release over prolonged periods. This review delineates the key advances in composite technologies that merge the concepts of depot polymeric scaffolds with liposome technology to overcome the limitations of conventional liposomes for pharmaceutical applications. PMID:21490759

  8. Use of liposomes as injectable-drug delivery systems.

    PubMed

    Ostro, M J; Cullis, P R

    1989-08-01

    The formation of liposomes and their application as delivery systems for injectable drugs are described. Liposomes are microscopic vesicles composed of one or more lipid membranes surrounding discrete aqueous compartments. These vesicles can encapsulate water-soluble drugs in their aqueous spaces and lipid-soluble drugs within the membrane itself. Liposomes release their contents by interacting with cells in one of four ways: adsorption, endocytosis, lipid exchange, or fusion. Liposome-entrapped drugs are distributed within the body much differently than free drugs; when administered intravenously to healthy animals and humans, most of the injected vesicles accumulate in the liver, spleen, lungs, bone marrow, and lymph nodes. Liposomes also accumulate preferentially at the sites of inflammation and infection and in some solid tumors; however, the reason for this accumulation is not clear. Four major factors influence liposomes' in vivo behavior and biodistribution: (1) liposomes tend to leak if cholesterol is not included in the vesicle membrane, (2) small liposomes are cleared more slowly than large liposomes, (3) the half-life of a liposome increases as the lipid dose increases, and (4) charged liposomal systems are cleared more rapidly than uncharged systems. The most advanced application of liposome-based therapy is in the treatment of systemic fungal infections, especially with amphotericin B. Liposomes are also under investigation for treatment of neoplastic disorders. Liposomes' uses in cancer therapy include encapsulation of known antineoplastic agents such as doxorubicin and methotrexate, delivery of immune modulators such as N-acetylmuramyl-L-alanine-D-isoglutamine, and encapsulation of new chemical entities that are synthesized with lipophilic segments tailored for insertion into lipid bilayers. Liposomal formulations of injectable antimicrobial agents and antineoplastic agents already are undergoing clinical testing, and most probably will receive

  9. A 2,4-dichlorophenoxyacetic acid degradation plasmid pM7012 discloses distribution of an unclassified megaplasmid group across bacterial species.

    PubMed

    Sakai, Yoriko; Ogawa, Naoto; Shimomura, Yumi; Fujii, Takeshi

    2014-03-01

    Analysis of the complete nucleotide sequence of plasmid pM7012 from 2,4-dichlorophenoxyacetic-acid (2,4-D)-degrading bacterium Burkholderia sp. M701 revealed that the plasmid had 582 142 bp, with 541 putative protein-coding sequences and 39 putative tRNA genes for the transport of the standard 20 aa. pM7012 contains sequences homologous to the regions involved in conjugal transfer and plasmid maintenance found in plasmids byi_2p from Burkholderia sp. YI23 and pBVIE01 from Burkholderia sp. G4. No relaxase gene was found in any of these plasmids, although genes for a type IV secretion system and type IV coupling proteins were identified. Plasmids with no relaxase gene have been classified as non-mobile plasmids. However, nucleotide sequences with a high level of similarity to the genes for plasmid transfer, plasmid maintenance, 2,4-D degradation and arsenic resistance contained on pM7012 were also detected in eight other megaplasmids (~600 or 900 kb) found in seven Burkholderia strains and a strain of Cupriavidus, which were isolated as 2,4-D-degrading bacteria in Japan and the United States. These results suggested that the 2,4-D degradation megaplasmids related to pM7012 are mobile and distributed across various bacterial species worldwide, and that the plasmid group could be distinguished from known mobile plasmid groups.

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

    NASA Astrophysics Data System (ADS)

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

    2013-07-01

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

  11. Temperature-dependent stability and DPPH scavenging activity of liposomal curcumin at pH 7.0.

    PubMed

    Niu, Yumeng; Ke, Dan; Yang, Qianqian; Wang, Xiaoyong; Chen, Zhiyun; An, Xueqin; Shen, Weiguo

    2012-12-01

    This paper investigated the influences of temperature on the stability and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity of curcumin encapsulated in liposome at pH 7.0. Liposomal curcumin showed higher stability and DPPH scavenging activity than free curcumin at 25°C. When temperature increased from 25 to 80°C, liposomal curcumin degraded more pronouncedly above the phase transition temperature (T(m)=45.7°C) of liposome than lower temperatures, suggesting a weaker curcumin protection from the liquid crystalline phase of phospholipid bilayer than that from the gel phase. Moreover, the presence of remarkable "jump" increases around T(m) in the values of observed pseudo-first-order rate constant and the percent of DPPH scavenging activity of liposomal curcumin indicated that the liquid crystalline phase of phospholipid bilayer is more beneficial for curcumin to reduce DPPH. This study reveals that changing the microstructure of encapsulation carrier may effectively control the properties of phytochemicals like curcumin. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Encapsulation, with high efficiency, of radioactive metal ions in liposomes.

    PubMed

    Hwang, K J; Merriam, J E; Beaumier, P L; Luk, K F

    1982-05-05

    The encapsulation of radioactive metalic cations, such as 111In3+ or 67Ga3+, in the internal aqueous compartment of liposomes can be achieved with an efficiency of about 90%. The efficient loading of a high specific activity of cations into liposomes involves the transport of 111In3+ or 67Ga3+ through the lipid bilayer to an encapsulated strong chelate, such as nitrilotriacetic acid, by 8-hydroxyquinoline, in conjunction with an efficient anion-exchange resin technique for the removal of the external cations. The efficiency of loading cations to liposomes is affected markedly by the concentration of 8-hydroxyquinoline-metal, and the presence of the chelating agents in the loading incubation mixture. However, the loading efficiency is not affected by the pH of the internal aqueous compartment of liposomes over a range of pH 5-9, the concentration of the liposomes, the method of liposomal preparation, the lamellar structure of the liposomes, and the composition of liposomes. Furthermore, the loading procedures do not appear to affect the size and the permeability of liposomes. There is a good agreement in the tissue distributions of the liposomes prepared by the present loading methods and those by the conventional method of encapsulation by sonication. Liposomes entrapping high specific activity of 67Ga3+ or 111In3+ will be useful for future studies of the in vivo kinetics of liposomes by the combined techniques of scintigraphic imaging and the gamma-ray perturbed angular correlation.

  13. Surface Engineering of Liposomes for Stealth Behavior

    PubMed Central

    Nag, Okhil K.; Awasthi, Vibhudutta

    2013-01-01

    Liposomes are used as a delivery vehicle for drug molecules and imaging agents. The major impetus in their biomedical applications comes from the ability to prolong their circulation half-life after administration. Conventional liposomes are easily recognized by the mononuclear phagocyte system and are rapidly cleared from the blood stream. Modification of the liposomal surface with hydrophilic polymers delays the elimination process by endowing them with stealth properties. In recent times, the development of various materials for surface engineering of liposomes and other nanomaterials has made remarkable progress. Poly(ethylene glycol)-linked phospholipids (PEG-PLs) are the best representatives of such materials. Although PEG-PLs have served the formulation scientists amazingly well, closer scrutiny has uncovered a few shortcomings, especially pertaining to immunogenicity and pharmaceutical characteristics (drug loading, targeting, etc.) of PEG. On the other hand, researchers have also begun questioning the biological behavior of the phospholipid portion in PEG-PLs. Consequently, stealth lipopolymers consisting of non-phospholipids and PEG-alternatives are being developed. These novel lipopolymers offer the potential advantages of structural versatility, reduced complement activation, greater stability, flexible handling and storage procedures and low cost. In this article, we review the materials available as alternatives to PEG and PEG-lipopolymers for effective surface modification of liposomes. PMID:24300562

  14. Treatment of Digital Ischemia with Liposomal Bupivacaine

    PubMed Central

    Raul Soberón, José; Duncan, Scott F.; Sternbergh, W. Charles

    2014-01-01

    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. PMID:24653844

  15. Comparison between liposomal formulations of amphotericin B.

    PubMed

    Adler-Moore, Jill P; Gangneux, Jean-Pierre; Pappas, Peter G

    2016-03-01

    Given the clinical success of commercial amphotericin B lipid products, investigators have begun making generic formulations of liposomal amphotericin B. Generic medicines are an attractive approach to help decrease the cost and accessibility to healthcare, provided that appropriate studies are performed to ensure bioequivalence with the parent product. This is of particular concern for liposomal drugs such as amphotericin B where liposomes are used as a carrier system to reduce the toxicity of the active agent. A favorable therapeutic profile for this form of the drug has to include the proper chemical composition along with strictly controlled manufacturing processes. Studies have shown that a comparison of liposomal amphotericin B products with different or the same chemical compositions, using different methods of production, will vary in size, and have significantly dissimilar in vitro and in vivo toxicities along with reduced efficacy. These results underscore the importance of establishing appropriate bioequivalence testing for liposome products to ensure uniformity of their therapeutic index. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Remotely controlled diffusion from magnetic liposome microgels.

    PubMed

    Hanuš, Jaroslav; Ullrich, Martin; Dohnal, Jiří; Singh, Mandeep; Stěpánek, František

    2013-04-02

    The reversible, temperature-dependent change in the permeability of a phospholipid bilayer has been used for controlling the diffusion rate of encapsulated molecular payload from liposomes. Liposomes were preloaded with a fluorescent dye and immobilized in calcium alginate hydrogel microparticles that also contained iron oxide nanoparticles. The composite microparticles were produced by a drop-on-demand inkjet method. The ability of iron oxide nanoparticles to locally dissipate heat upon exposure to a radio-frequency (RF) alternating magnetic field was used to control the local temperature and therefore diffusion from the liposomes in a contactless way using an RF coil. Several different release patterns were realized, including repeated on-demand release. The internal structure of the composite alginate-liposome-magnetite microparticles was investigated, and the influence of microparticle concentration on the heating rate was determined. In order to achieve a temperature rise required for the liposome membrane melting, the concentration of alginate beads should be at least 25% of their maximum packing density for the nanoparticle concentration and specific absorption rate used.

  17. Magnetic nanoparticles for "smart liposomes".

    PubMed

    Nakayama, Yoshitaka; Mustapić, Mislav; Ebrahimian, Haleh; Wagner, Pawel; Kim, Jung Ho; Hossain, Md Shahriar Al; Horvat, Joseph; Martinac, Boris

    2015-12-01

    Liposomal drug delivery systems (LDDSs) are promising tools used for the treatment of diseases where highly toxic pharmacological agents are administered. Currently, destabilising LDDSs by a specific stimulus at a target site remains a major challenge. The bacterial mechanosensitive channel of large conductance (MscL) presents an excellent candidate biomolecule that could be employed as a remotely controlled pore-forming nanovalve for triggered drug release from LDDSs. In this study, we developed superparamagnetic nanoparticles for activation of the MscL nanovalves by magnetic field. Synthesised CoFe2O4 nanoparticles with the radius less than 10 nm were labelled by SH groups for attachment to MscL. Activation of MscL by magnetic field with the nanoparticles attached was examined by the patch clamp technique showing that the number of activated channels under ramp pressure increased upon application of the magnetic field. In addition, we have not observed any cytotoxicity of the nanoparticles in human cultured cells. Our study suggests the possibility of using magnetic nanoparticles as a specific trigger for activation of MscL nanovalves for drug release in LDDSs.

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

    NASA Astrophysics Data System (ADS)

    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.

  19. [Evaluating thrombolytic efficacy and thrombus targetability of RGDS-liposomes encapsulating subtilisin FS33 in vivo].

    PubMed

    Wang, Chengtao; Ji, Baoping; Cao, Yanping; Sun, Baoguo; Liu, Xudong

    2010-04-01

    A novel fibrinolytic enzyme subtilisin FS33, which exhibits much higher activity for decomposing fibrin than urokinase, was purified from Douchi, a traditional soybean-fermented food in China. In order to increase bio-utilization and thrombus targetability of subtilisin FS33 labeled by fluorescein isothiocyanate (FITC), the surface modified liposomes encapsulating subtilisin FS33 and FITC with a synthetic peptide Arg-Gly-Asp-Ser (RGDS), being putatively a specific antagonist of fibrinogen receptor on platelet membrane, were prepared and used to evaluate the therapeutic efficacy in a rat model thrombotic carotid artery. The arterial thrombosis was induced by applying two pieces of filter paper (1 x 2 cm) saturated with 10% of ferric chloride (FeCl3). The rats were infused via the jugular vein with either liposomes carrying BSA (control group) or RGDS-liposomes carrying subtilisin FS33 at doses of 2000 and 4000 U/kg. The plasma of the group infused with RGDS-liposomes showed higher antithrombotic and fibrinolytic activity than did the control group within 15-120 min after infusing. The higher the dose was gived, the higher the activity was shown. APTT(activiated partial thromboplastin time), PT (prothrombin time) and TT (thrombin time) were extended remarkably (P < 0.05, P < 0.01), and FDP (fibrinogen degradation products) also increased greatly (P < 0.01), while ELT (euglobulinlysis time) decreased obviously (P < 0.05). FITC content in heart and brain evidently increased (P < 0.05), and results of D-dimer test were all positive. In addition, the venous thrombi in brain and kidney were dissolved totally or partly as observed by patholgical section. All these indicated that subtilisin FS33 enhanced the antithrombotic and fibrinolytic activities in rat, and RGDS-liposomes improved, in a certain degree, the thrombolytic specificity for targeting to thrombus.

  20. Dressing liposomal particles with chitosan and poly(vinylic alcohol) for oral vaccine delivery.

    PubMed

    Rescia, Vanessa C; Takata, Célia S; de Araujo, Pedro S; Bueno da Costa, Maria H

    2011-03-01

    Liposomes have been used as adjuvants since 1974. One major limitation for the use of liposomes in oral vaccines is the lipid structure instability caused by enzyme activities. Our aim was to combine liposomes that could encapsulate antigens (i.e., Dtxd, diphtheria toxoid) with chitosan, which protects the particles and promotes mucoadhesibility. We employed physical techniques to understand the process by which liposomes (SPC: Cho, 3:1) can be sandwiched with chitosan (Chi) and stabilized by PVA (poly-vinylic alcohol), which are biodegradable, biocompatible polymers. Round, smooth-surfaced particles of REVs-Chi (reversed-phase vesicles sandwiched by Chi) stabilized by PVA were obtained. The REVs encapsulation efficiencies (Dtxd was used as the antigen) were directly dependent on the Chi and PVA present in the formulation. Chi adsorption on the REVs surface was accompanied by an increase of ζ-potential. In contrast, PVA adsorption on the REVs-Chi surface was accompanied by a decrease of ζ-potential. The presence of Dtxd increased the Chi surface-adsorption efficiency. The PVA affinity by mucine was 2,000 times higher than that observed with Chi alone and did not depend on the molecule being in solution or adsorbed on the liposomal surface. The liberation of encapsulated Dtxd was retarded by encapsulation within REVs-Chi-PVA. These results lead us to conclude that these new, stabilized particles were able to be adsorbed by intestinal surfaces, resisted degradation, and controlled antigen release. Therefore, REVs-Chi-PVA particles can be used as an oral delivery adjuvant.

  1. Comparative effect and fate of non-entrapped and liposome-entrapped neuraminidase injected into rats

    PubMed Central

    Gregoriadis, Gregory; Putman, Daphne; Louis, Loizos; Neerunjun, Diane

    1974-01-01

    Non-entrapped and liposome-entrapped Clostridium perfringens neuraminidase (0.5–0.6 unit) was injected into rats and its fate as well as its effect on plasma and erythrocyte N-acetylneuraminic acid was investigated. The following observations were made. (1) Although removal of both non-entrapped and liposome-entrapped neuraminidase from the circulation was completed within 5h after injection, their recovery in tissues was distinctly different; 7–10% of the injected non-entrapped enzyme was found in the liver and none in the liver lysosomal fraction or the spleen. In contrast, 20–26% of the liposome-entrapped enzyme was found in the liver of which 60–69% was in the lysosomal fraction. Spleen contained 3.6–5.0% of the enzyme. (2) The presence of the non-entrapped neuraminidase in blood led to the extensive desialylation of plasma and to a decrease in the concentration or total removal from the circulation of some of the plasma glycoproteins. (3) Injection of non-entrapped neuraminidase also led to the partial desialylation of erythrocytes the life span of which was diminished and their uptake by the liver and spleen augmented. (4) Entrapment of neuraminidase in liposomes before its injection prevented the enzyme from acting on its substrate in plasma or on the erythrocyte surface, and values obtained for plasma glycoproteins and erythrocyte survival were similar to those observed in control rats. (5) Entrapment in liposomes of therapeutic hydrolases intended for the degradation of substances stored within the tissue lysosomes of patients with storage diseases could prevent the potentially hazardous enzymic action of hydrolases in blood and at the same time direct the enzymes to the intracellular sites where they are needed. ImagesPLATE 1PLATE 2 PMID:4375965

  2. Imaging-based analysis of liposome internalization to macrophage cells: Effects of liposome size and surface modification with PEG moiety.

    PubMed

    Lee, Jae Sun; Hwang, Sang Youn; Lee, E K

    2015-12-01

    Liposome is one of the frequently used carriers for active targeting systems in vivo. Such parameters as its size, surface charge, and surface modifiers are known to influence the liposome uptake by macrophage cells. In this study, we investigated the effects of liposome size and polyethylene glycol (PEG) surface modifier on the liposomal internalization to murine macrophage (RAW-264.7), by using an imaging analysis technique. Three different sized liposomes (100, 200, and 400 nm in nominal diameter) labeled with rhodamine fluorescence were used. Liposome internalization appeared to reach a pseudo-steady plateau in about 5h incubation, and most of the internalized liposomes were seen to accumulate in the cytosol including cellular extensions. The maximum fluorescent density from the internalized liposomes was similar between 100 nm and 200 nm liposomes. However, that of the larger 400 nm liposome was approximately 1.7 times higher than the others, confirming the previous report that the larger the liposomes are the higher the degree of internalization is. When the outside of the 200 nm liposomes was modified with biocompatible anchor molecule (BAM) consisting of PEG (ca. 2kD molecular weight) moiety, the endocytosis was indeed reduced by about 2.1-fold, despite the increase of the hydrodynamic size due to BAM conjugation. This fluorescence-based cellular imaging analysis can be used to quantitatively monitor and optimize cellular internalization systems.

  3. Liposomes targeted by fusion phage proteins.

    PubMed

    Jayanna, Prashanth K; Torchilin, Vladimir P; Petrenko, Valery A

    2009-03-01

    Targeting of nanocarriers has long been sought after to improve the therapeutic indices of anticancer drugs. Here we provide the proof of principle for a novel approach of nanocarrier targeting through their fusion with target-specific phage coat proteins. The source of the targeted phage coat proteins are landscape phage libraries--collections of recombinant filamentous phages with foreign random peptides fused to all 4000 copies of the major coat protein. We exploit in our approach the intrinsic physicochemical properties of the phage major coat protein as a typical membrane protein. Landscape phage peptides specific for specific tumors can be obtained by affinity selection, and purified fusion coat proteins can be assimilated into liposomes to obtain specific drug-loaded nanocarriers. As a paradigm for inceptive experiments, a streptavidin-specific phage peptide selected from a landscape phage library was incorporated into approximately 100-nm liposomes. Targeting of liposomes was proved by their specific binding to streptavidin-coated beads.

  4. Dehydration resistance of liposomes containing trehalose glycolipids

    NASA Astrophysics Data System (ADS)

    Nyberg, Kendra; Goulding, Morgan; Parthasarathy, Raghuveer

    2010-03-01

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

  5. Bioavailability of Polyphenol Liposomes: A Challenge Ahead

    PubMed Central

    Mignet, Nathalie; Seguin, Johanne; Chabot, Guy G.

    2013-01-01

    Dietary polyphenols, including flavonoids, have long been recognized as a source of important molecules involved in the prevention of several diseases, including cancer. However, because of their poor bioavailability, polyphenols remain difficult to be employed clinically. Over the past few years, a renewed interest has been devoted to the use of liposomes as carriers aimed at increasing the bioavailability and, hence, the therapeutic benefits of polyphenols. In this paper, we review the causes of the poor bioavailability of polyphenols and concentrate on their liposomal formulations, which offer a means of improving their pharmacokinetics and pharmacodynamics. The problems linked to their development and their potential therapeutic advantages are reviewed. Future directions for liposomal polyphenol development are suggested. PMID:24300518

  6. Prolonged blood circulation of methotrexate by modulation of liposomal composition.

    PubMed

    Hong, M S; Lim, S J; Lee, M K; Kim, Y B; Kim, C K

    2001-01-01

    Prolonged circulation by liposomal incorporation has been shown to enhance the therapeutic efficacy of drugs in many cases. The purpose of this study was to investigate whether the prolonged circulation of methotrexate (MTX) can be achieved by modulating the liposomal compositions. Various compositions of liposomes were prepared with 2:1 of phosphatidylcholine (PC) and cholesterol (CH) with or without distearoylphosphatidyl-ethanolamine-N-poly(ethyleneglycol) 2000 (DSPE-PEG). The MTX encapsulation efficiency depended on the type of PC used. It also appeared to increase by inclusion of DSPE-PEG. The size of liposomes decreased by the inclusion of DSPE-PEG. The inclusion of DSPE-PEG lowered the plasma-induced release of MTX from EggPC/CH and DPPC/CH liposomes, suggesting its enhancement effect on the liposomal stability. After intravenous injection to rats, the pharmacokinetics and biodistribution of MTX were significantly changed by liposomal incorporation and also by the composition of liposomes. The total body clearance of MTX incorporated in EggPC/CH, DPPC/CH, EggPC/CH/DSPE-PEG, and DPPC/CH/DSPE-PEG liposomes decreased 4.4-, 14.9-, 24.5-, and 53.1-fold, compared with that of free MTX. The ratio of MTX concentration in blood to liver and spleen after injection of DPPC/CH, EggPC/CH/DSPE-PEG, and DPPC/CH/DSPE-PEG liposomes was 5.4-, 8.5-, and 13.5-fold higher than that of EggPC/CH liposomes. Furthermore, the accumulation of MTX in the kidney, one of the organs in which MTX exhibits its toxicity, was significantly lowered by liposomal incorporation, especially by DSPE-PEG-containing liposomes. Taken together, DPPC/CH/DSPE-PEG liposomes most effectively prolonged the blood circulation, and reduced hepatosplenic and kidney uptake of MTX. DPPC/CH/DSPE-PEG liposomes may have potential as an efficient delivery system for MTX.

  7. Compartmentalization of Gd liposomes: the quenching effect explained.

    PubMed

    Guenoun, Jamal; Doeswijk, Gabriela N; Krestin, Gabriel P; Bernsen, Monique R

    2016-01-01

    Cationic liposomes carrying high [Gd] can be used as efficient cell-labeling agents. In a compartmentalized state, Gd can cause signal loss (relaxivity quenching). The contributions of liposomal [Gd], size and compartmentalization state to relaxivity quenching were assessed. The dependency of signal intensity (SI) on intraliposomal [Gd] was assessed comparing three different [Gd] (0.3, 0.6 and 1.0 M Gd) in both small (80 nm) and large (120 nm) cationic liposomes. In addition, five compartmentalization states were compared: free Gd, intact Gd liposomes, ruptured Gd liposomes, Gd liposomes in intact cells and Gd liposomes in ruptured cells (simulating cell death). Gd also causes R2 effects, which is often overlooked. Therefore, both R1 and R2 relaxation rates of a dilution range were measured by T1 and T2 mapping on a 7 T clinical scanner. Less is more. As the unidirectional water efflux rate (outbound across the liposome membrane, κle) is proportional to the surface:volume ratio, smaller liposomes yielded a consistently higher R1 than larger liposomes. For equal voxel [Gd] less concentrated liposomes (0.3 M Gd) yielded higher R1/R2 ratio because of the higher extraliposomal water fraction (vl ). Gd exhibits a dualistic behavior: from hypointensity to hyperintensity to hypointensity, with decreasing [Gd]. Regarding compartmentalization, fewer membrane barriers means a higher R1 /R2 ratio. Gd liposomes exhibit a versatile contrast behavior, dependent on the compartmentalization state, liposomal size, intraliposomal [Gd] and liposome number. Both R1 and R2 effects contribute to this. The versatility allows one to tailor the optimal liposomal formulation to desired goals in cell labeling and tracking.

  8. Liposomal boron delivery for neutron capture therapy.

    PubMed

    Nakamura, Hiroyuki

    2009-01-01

    Tumor cell destruction in boron neutron capture therapy (BNCT) is due to the nuclear reaction between (10)B and thermal neutrons. The thermal neutrons have an energy of 0.025 eV, clearly below the threshold energy required to ionize tissue components. However, neutron capture by (10)B produces lithium ion and helium (alpha-particles), which are high linear energy transfer (LET) particles, and dissipate their kinetic energy before traveling one cell diameter (5-9 microm) in biological tissues, ensuring their potential for precise cell killing. BNCT has been applied clinically for the treatment of malignant brain tumors, malignant melanoma, head and neck cancer, and hepatoma using two boron compounds: sodium borocaptate (Na(2)(10)B(12)H(11)SH; Na(2)(10)BSH) and l-p-boronophenylalanine (l-(10)BPA). These low molecular weight compounds are cleared easily from the cancer cells and blood. Therefore, high accumulation and selective delivery of boron compounds into tumor tissues are most important to achieve effective BNCT and to avoid damage of adjacent healthy cells. Much attention has been focused on the liposomal drug delivery system (DDS) as an attractive, intelligent technology of targeting and controlled release of (10)B compounds. Two approaches have been investigated for incorporation of (10)B into liposomes: (1) encapsulation of (10)B compounds into liposomes and (2) incorporation of (10)B-conjugated lipids into the liposomal bilayer. Our laboratory has developed boron ion cluster lipids for application of the latter approach. In this chapter, our boron lipid liposome approaches as well as recent developments of the liposomal boron delivery system are summarized.

  9. Recent Trends of Polymer Mediated Liposomal Gene Delivery System

    PubMed Central

    Lee, Sang-Soo; George Priya Doss, C.; Yagihara, Shin; Kim, Do-Young

    2014-01-01

    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. PMID:25250340

  10. Method of encapsulating polyaminopolycarboxylic acid chelating agents in liposomes

    DOEpatents

    Rahman, Yueh Erh

    1977-11-10

    A method is provided for transferring a polyaminopolycarboxylic acid chelating agent across a cellular membrane by encapsulating the charged chelating agent within liposomes, which liposomes will be taken up by the cells, thereby transferring the chelating agent across the cellular membrane. The chelating agent is encapsulated within liposomes by drying a lipid mixture to form a thin film and wetting the lipid film with a solution containing the chelating agent. Mixing then results in the formation of a suspension of liposomes encapsulating the chelating agent, which liposomes can then be separated.

  11. Microfluidic-Enabled Liposomes Elucidate Size-Dependent Transdermal Transport

    PubMed Central

    Junqueira, Mariana; Vreeland, Wyatt N.; Quezado, Zenaide; Finkel, Julia C.; DeVoe, Don L.

    2014-01-01

    Microfluidic synthesis of small and nearly-monodisperse liposomes is used to investigate the size-dependent passive transdermal transport of nanoscale lipid vesicles. While large liposomes with diameters above 105 nm are found to be excluded from deeper skin layers past the stratum corneum, the primary barrier to nanoparticle transport, liposomes with mean diameters between 31–41 nm exhibit significantly enhanced penetration. Furthermore, multicolor fluorescence imaging reveals that the smaller liposomes pass rapidly through the stratum corneum without vesicle rupture. These findings reveal that nanoscale liposomes with well-controlled size and minimal size variance are excellent vehicles for transdermal delivery of functional nanoparticle drugs. PMID:24658111

  12. Optimization of liposomal encapsulation for ceftazidime for developing a potential eye drop formulation.

    PubMed

    Wijesooriya, Chamari; Budai, Marianna; Budai, Lívia; Szilasi, Magdolna E; Petrikovics, Ilona

    2013-06-01

    Ceftazidime is a broad spectrum third generation cephalosporin antibiotic which is effective mainly against Gram-negative bacteria such as Pseudomonas aeruginosa, Acinetobacter and Enterobacteriaceae, the pathogens which most often cause ophthalmological infections. Unlike other commonly used beta lactam antibiotics, ceftazidime is resistant to several types of beta lactamases (e.g., TEM, SHV and PSE-1). Because of these advantages, ceftazidime is used in the treatment of eye infections. However, ceftazidime undergoes rapid degradation in aqueous solutions therefore eye drops containing ceftazidime in aqueous solutions are not commercially manufactured. In the present study, liposomal encapsulations of ceftazidime with various lipid compositions, hydrating solutions and pH-values have been studied in order to optimize liposomal composition for a potential eye drop formulation.

  13. Ultrasound-mediated intracellular drug delivery using microbubbles and temperature-sensitive liposomes.

    PubMed

    Yudina, A; de Smet, M; Lepetit-Coiffé, M; Langereis, S; Van Ruijssevelt, L; Smirnov, P; Bouchaud, V; Voisin, P; Grüll, H; Moonen, C T W

    2011-11-07

    A novel two-step protocol for intracellular drug delivery has been evaluated in vitro. As a first step TO-PRO-3 (a cell-impermeable dye that displays a strong fluorescence enhancement upon binding to nucleic acids) encapsulated in thermosensitive liposomes was released after heating to 42°C. A second step consisted of ultrasound-mediated local permeabilization of cell membrane allowing TO-PRO-3 internalization observable as nuclear staining. Only the combination of two consecutive steps - heating and sonication in the presence of SonoVue microbubbles led to the model drug TO-PRO-3 release from the thermosensitive liposomes and its intracellular uptake. This protocol is potentially beneficial for the intracellular delivery of cell impermeable drugs that suffer from rapid clearance and/or degradation in blood and are not intrinsically taken up by cells.

  14. Photostabilization of 1,4-dihydropyridine antihypertensives by incorporation into beta-cyclodextrin and liposomes.

    PubMed

    Ragno, G; Risoli, A; Ioele, G; Cione, E; De Luca, M

    2006-01-01

    Inclusion compounds of eleven dihydropyridine drugs were formed and investigated for protection against photo-induced drug degradation. Formulations of cyclodextrins and liposomes were prepared and their photoprotective ability for the encapsulated drug was monitored. Drug photodegradation was spectrophotometrically followed during exposure of the formulations to light of a Xenon lamp. ICH guidelines for photostability testing were applied. A comparison with common pharmaceutical formulations revealed optimal protection for both formulations. The use of the liposome and cyclodextrin inclusion complexes resulted in a mean drug recovery of 77 and more then 90% respectively, after a light exposure until to 30 minutes with an intensity of 21 kJ x min(-1) m(-2). Lercanidipine and Manidipine only did not show a satisfactory increase of photostabilization in the studied supramolecular complexes, due to their low inclusion in both the systems.

  15. Gene transfection efficiency into dendritic cells is influenced by the size of cationic liposomes/DNA complexes.

    PubMed

    Inoh, Yoshikazu; Nagai, Mie; Matsushita, Kayo; Nakanishi, Mamoru; Furuno, Tadahide

    2017-05-01

    Cationic liposomes have attracted recent attention as DNA vaccine carriers that can target dendritic cells (DCs). In general, cationic liposome/DNA complexes (lipoplexes) are taken up by various cells via clathrin-mediated endocytosis, caveolae-mediated endocytosis, macropinocytosis, or phagocytosis, with the mode of endocytosis determining further intracellular trafficking pathways. Moreover, the physicochemical properties of cationic lipoplexes, including lipid composition, shape, size, and charge, influence transfection efficiency, affecting uptake and subsequent intracellular pathways. To develop cationic liposomes as potential DNA vaccine carriers, the objective of this study was to study the effect of lipoplex size on DNA transfection efficiency in DCs. We explored the size-dependent endocytosis pathway and the intracellular trafficking of cationic lipoplexes using bone marrow derived dendritic cells (BMDCs). Our results indicated that small-sized lipoplexes (approximately 270nm diameter) were taken up by BMDCs via caveolae-mediated endocytosis, which led to a non-degradative pathway, whereas larger-sized lipoplexes (approximately 500nm diameter) were taken up by BMDCs via clathrin-mediated endocytosis and micropinocytosis, which led to a lysosomal degradation pathway. These findings suggest that, by regulating the size of lipoplexes, it may be possible to develop cationic liposomes as DNA vaccine therapies for targeting DCs. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Liposomes from hydrogenated soya lecithin formed in sintered glass pores.

    PubMed

    Zawada, Zygmunt H

    2012-01-01

    Possible complete closure of hydrophilic drug solutions in liposomes with required dimensions is the aim of variety liposome techniques. The ease of separating medication-loaded liposomes from liposome suspension to achieve an appropriate drug concentration in the final preparation is also desired. This paper describes the use of liposome preparation method, called reverse-phase evaporation, which leads to practical achievement of the earlier mentioned objectives. Preparation process is performed in an appropriately designed device. In optimal conditions of liposome preparation the final encapsulation efficiency of hydrophilic drug solution amounted to 50% in liposomes with a diameter in the range of a few micrometers up to 250 nm. The diameter of terminal liposomes is a simple function of relative amount of the lipid used and the degree of emulsion emulsification w/o at the beginning of liposome preparation. The density of the concentrated drug solution trapped in liposomes is usually higher than that of the buffer. Therefore, the loaded liposomes may be easily separated from non-trapped material by using of a simple sedimentation at 30000 x g. Density of aqueous drug solution insufficient to effective centrifugation can be magnified with an appropriate quantity of sucrose solution before encapsulation.

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

    NASA Astrophysics Data System (ADS)

    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.

  18. Liposomes as signal amplification reagents for bioassays in microfluidic channels.

    PubMed

    Locascio, Laurie E; Hong, Jennifer S; Gaitan, Michael

    2002-03-01

    Liposomes with encapsulated carboxyfluorescein were used in an affinity-based assay to provide signal amplification for small-volume fluorescence measurements. Microfluidic channels were fabricated by imprinting in a plastic substrate material, poly(ethylene terephthalate glycol) (PETG), using a silicon template imprinting tool. Streptavidin was linked to the surface through biotinylated-protein for effective immobilization with minimal nonspecific adsorption of the liposome reagent. Lipids derivatized with biotin were incorporated into the liposome membrane to make the liposomes reactive for affinity assays. Specific binding of the liposomes to microchannel walls, dependence of binding on incubation time, and nonspecific adsorption of the liposome reagent were evaluated. The results of a competitive assay employing liposomes in the microchannels are presented.

  19. Determination of liposome size: a tool for protein reconstitution.

    PubMed

    Vojta, Aleksandar; Scheuring, Johannes; Neumaier, Nikolaus; Mirus, Oliver; Weinkauf, Sevil; Schleiff, Enrico

    2005-12-01

    Reconstitution of proteins into liposomes is a widespread approach to analyzing their biological function. Many protocols exist for this procedure and for the subsequent analysis of proteins. Here, we establish a procedure for preparation and analysis of liposomes with a lipid composition reflecting the outer envelope of chloroplasts. First, the stability of the liposomes in different buffer systems was investigated to provide information for the storage of the reconstituted system. Then, the size of the liposomes created by filtration through a polycarbonate filter dependent on the lipid composition was analyzed. Subsequently, solubilization of the liposomes composed of lipids with the outer envelope composition by dodecylmaltoside and octylglucoside as a preceding step of reconstitution was studied. Finally, we developed a straightforward method to determine the size of liposomes by absorption spectroscopy. The described setup allows the construction of reconstitution protocols, including the final determination of the liposome size.

  20. Characterisation of gene delivery using liposomal bubbles and ultrasound

    NASA Astrophysics Data System (ADS)

    Koshima, Risa; Suzuki, Ryo; Oda, Yusuke; Hirata, Keiichi; Nomura, Tetsuya; Negishi, Yoichi; Utoguchi, Naoki; Kudo, Nobuki; Maruyama, Kazuo

    2011-09-01

    The combination of nano/microbubbles and ultrasound is a novel technique for a non-viral gene deliver. We have previously developed novel ultrasound sensitive liposomes (Bubble liposomes) which contain the ultrasound imaging gas perfluoropropane. In this study, Bubble liposomes were compared with cationic lipid (CL)-DNA complexes as potential gene delivery carriers into tumors in vivo. The delivery of genes by bubble liposomes depended on the intensity of the applied ultrasound. The transfection efficiency plateaued at 0.7 W/cm2 ultrasound intensity. Bubble liposomes efficiently transferred genes into cultured cells even when the cells were exposed to ultrasound for only 1 s. In addition, bubble liposomes were able to introduce the luciferase gene more effectively than CL-DNA complexes into mouse ascites tumor cells. We conclude that the combination of Bubble liposomes and ultrasound is a good method for gene transfer in vivo.

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

    PubMed

    Janicki, Joseph J; Chancellor, Michael B; Kaufman, Jonathan; Gruber, Michele A; Chancellor, David D

    2016-03-18

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

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

    PubMed Central

    Janicki, Joseph J.; Chancellor, Michael B.; Kaufman, Jonathan; Gruber, Michele A.; Chancellor, David D.

    2016-01-01

    Bladder drug delivery via catheter instillation is a widely used treatment for recurrence of superficial bladder cancer. Intravesical instillation of liposomal botulinum toxin has recently shown promise in the treatment of overactive bladder and interstitial cystitis/bladder pain syndrome, and studies of liposomal tacrolimus instillations show promise in the treatment of hemorrhagic cystitis. Liposomes are lipid vesicles composed of phospholipid bilayers surrounding an aqueous core that can encapsulate hydrophilic and hydrophobic drug molecules to be delivered to cells via endocytosis. This review will present new developments on instillations of liposomes and liposome-encapsulated drugs into the urinary bladder for treating lower urinary tract dysfunction. PMID:26999210

  3. Steric stabilization of fusogenic liposomes by a low-pH sensitive PEG--diortho ester--lipid conjugate.

    PubMed

    Guo, X; Szoka, F C

    2001-01-01

    We describe the synthesis and characterization of a pH-sensitive poly(ethylene glycol)-diortho ester-distearoyl glycerol conjugate (POD). POD was prepared by a one-step synthesis, and its acid sensitivity characterized by TLC. The conjugate was found to be stable at neutral pH for greater than 3 h but degraded completely within 1 h at pH 5. Liposomes composed of 10% of POD and 90% of a fusogenic lipid, dioleoyl phosphatidylethanolamine (DOPE) were readily prepared and remained stable for up to 12 h in neutral buffer as shown by photon correlation spectrometry and a liposome contents leakage assay. However, when POD/DOPE liposomes were incubated in acidic pH as mild as 5.5, they aggregated and released most of their contents within 30 min. The kinetics of content release from POD/DOPE liposomes consisted of two phases, a lag phase, and a burst phase. The lag phase is inversely correlated with pH and the logarithm of the length of lag phase showed a linear relationship with the buffer pH. When the POD/DOPE liposomes were incubated in 75% of fetal bovine serum at 37 degrees C, they remained as stable as traditional PEG-grafted liposomes for 12 h but released 84% of the encapsulated ANTS in the following 4 h. Upon intravenous administration into mice, liposomes composed of 10% POD and 90% DOPE were cleared from circulation by a one-compartment kinetics with a half-life of about 200 min. POD is an example for the design of a novel category of pH sensitive lipids composed of a headgroup, an acid-labile diortho ester linker and a hydrophobic tail. The uniquely fast degradation kinetics of POD at pH 5-6 and its ability to stabilize liposomes in serum make the conjugate suitable for applications for triggered drug release systems targeted to mildly acidic bio-environments such as endosomes, solid tumors, and inflammatory tissues.

  4. Targeting anti-transferrin receptor antibody (OX26) and OX26-conjugated liposomes to brain capillary endothelial cells using in situ perfusion.

    PubMed

    Gosk, Sara; Vermehren, Charlotte; Storm, Gert; Moos, Torben

    2004-11-01

    Brain capillary endothelial cells (BCECs) express transferrin receptors. The uptake of a potential drug vector (OX26, or anti-transferrin receptor antibody IgG2a) conjugated to polyethyleneglycol-coated liposomes by BCECs was studied using in situ perfusion in 18-day-old rats in which the uptake of OX26 is almost twice as high as in the adult rat. Using radio-labeling, the uptake of OX26 by BCECs after 15-minute perfusion was approximately 16 times higher than that of nonimmune IgG2a (Ni-IgG2a). OX26 and OX26-conjugated liposomes selectively distributed to BCECs, leaving choroid plexus epithelium, neurons, and glia unlabeled. Ni-IgG2a and unconjugated liposomes did not reveal any labeling of BCECs. The labeling of BCECs by OX26 was profoundly higher than that of transferrin. Perfusion with albumin for 15 minutes did not reveal any labeling of neurons or glia, thus confirming the integrity of the blood-brain barrier. The failure to label neurons and glia shows that OX26 and OX26-conjugated liposomes did not pass through BCECs. The expression of transferrin receptors by endothelial cells selective to the brain qualifies OX26 as a candidate for blood-to-endothelium transport. A specifically designed formulation of liposomes may allow for their degradation within BCECs, leading to subsequent transport of liposomal cargo further into the brain.

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

    PubMed

    Franzen, Ulrik; Østergaard, Jesper

    2012-12-07

    Liposomes are self-assembled phospholipid vesicles and have numerous research and therapeutic applications. In the pharmaceutical and biomedical sciences liposomes find use as models of biological membranes, partitioning medium and as drug carriers. The present review addresses the use of capillary electrophoresis and liposome electrokinetic chromatography for the characterization of liposomes in a pharmaceutical context. Capillary electrophoretic techniques have been used for the measurement of electrophoretic mobility, which provides information on liposome surface charge, size and membrane permeability of liposomes. The use of liposome electrokinetic chromatography and capillary electrophoresis for determination of liposome/water partitioning and characterization of drug-liposome interactions is reviewed. A number of studies indicate that capillary electrophoresis may have a role in the characterization of liposome drug delivery systems, e.g., for the investigation of encapsulation efficiency and drug leakage. The well-known characteristics of capillary electrophoresis, i.e., low sample volume requirement, high separation efficiency in aqueous media without a stationary phase, minimal sample preparation, and a high degree of automation, makes it an attractive approach in liposome research.

  6. Predicting the influence of liposomal lipid composition on liposome size, zeta potential and liposome-induced dendritic cell maturation using a design of experiments approach.

    PubMed

    Soema, Peter C; Willems, Geert-Jan; Jiskoot, Wim; Amorij, Jean-Pierre; Kersten, Gideon F

    2015-08-01

    In this study, the effect of liposomal lipid composition on the physicochemical characteristics and adjuvanticity of liposomes was investigated. Using a design of experiments (DoE) approach, peptide-containing liposomes containing various lipids (EPC, DOPE, DOTAP and DC-Chol) and peptide concentrations were formulated. Liposome size and zeta potential were determined for each formulation. Moreover, the adjuvanticity of the liposomes was assessed in an in vitro dendritic cell (DC) model, by quantifying the expression of DC maturation markers CD40, CD80, CD83 and CD86. The acquired data of these liposome characteristics were successfully fitted with regression models, and response contour plots were generated for each response factor. These models were applied to predict a lipid composition that resulted in a liposome with a target zeta potential. Subsequently, the expression of the DC maturation factors for this lipid composition was predicted and tested in vitro; the acquired maturation responses corresponded well with the predicted ones. These results show that a DoE approach can be used to screen various lipids and lipid compositions, and to predict their impact on liposome size, charge and adjuvanticity. Using such an approach may accelerate the formulation development of liposomal vaccine adjuvants.

  7. Properties of liposomal membranes containing lysolecithin.

    PubMed

    Kitagawa, T; Inoue, K; Nojima, S

    1976-06-01

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

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

    PubMed Central

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

    2016-01-01

    The objective of the present study was to investigate the influence of the encapsulation efficiency and size of liposome on the oral bioavailability of griseofulvin-loaded liposomes. Griseofulvin-loaded liposomes with desired characteristics were prepared from pro-liposome using various techniques. To study the effect of encapsulation efficiency, three preparations of griseofulvin, namely, griseofulvin aqueous suspension and two griseofulvin-loaded liposomes with different amounts of 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. PMID:27571096

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

    PubMed

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

    2016-08-26

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

  10. Nanocomposite liposomes containing quantum dots and anticancer drugs for bioimaging and therapeutic delivery: a comparison of cationic, PEGylated and deformable liposomes

    NASA Astrophysics Data System (ADS)

    Wen, Chih-Jen; Sung, Calvin T.; Aljuffali, Ibrahim A.; Huang, Yu-Jie; Fang, Jia-You

    2013-08-01

    Multifunctional liposomes loaded with quantum dots (QDs) and anticancer drugs were prepared for simultaneous bioimaging and drug delivery. Different formulations, including cationic, PEGylated and deformable liposomes, were compared for their theranostic efficiency. We had evaluated the physicochemical characteristics of these liposomes. The developed liposomes were examined using experimental platforms of cytotoxicity, cell migration, cellular uptake, in vivo melanoma imaging and drug accumulation in tumors. The average size of various nanocomposite liposomes was found to be 92-134 nm. Transmission electron microscopy confirmed the presence of QDs within liposomal bilayers. The incorporation of polyethylene glycol (PEG) and Span 20 into the liposomes greatly increased the fluidity of the bilayers. The liposomes provided sustained release of camptothecin and irinotecan. The cytotoxicity and cell migration assay demonstrated superior activity of cationic liposomes compared with other carriers. Cationic liposomes also showed a significant fluorescence signal in melanoma cells after internalization. The liposomes were intratumorally administered to a melanoma-bearing mouse. Cationic liposomes showed the brightest fluorescence in tumors, followed by classical liposomes. This signal could last for up to 24 h for cationic nanosystems. Intratumoral accumulation of camptothecin from free control was 35 nmol g-1 it could be increased to 50 nmol g-1 after loading with cationic liposomes. However, encapsulation of irinotecan into liposomes did not further increase intratumoral drug accumulation. Cationic liposomes were preferable to other liposomes as nanocarriers in both bioimaging and therapeutic approaches.

  11. Liposomal Encapsulated Rhodomyrtone: A Novel Antiacne Drug

    PubMed Central

    Chorachoo, Julalak; Amnuaikit, Thanaporn; Voravuthikunchai, Supayang P.

    2013-01-01

    Rhodomyrtone isolated from the leaves of Rhodomyrtus tomentosa possesses antibacterial, anti-inflammatory, and anti-oxidant activities. Since rhodomyrtone is insoluble in water, it is rather difficult to get to the target sites in human body. Liposome exhibited ability to entrap both hydrophilic and hydrophobic compounds and easily penetrate to the target site. The present study aimed to develop a novel liposomal encapsulated rhodomyrtone formulations. In addition, characterization of liposome, stability profiles, and their antiacne activity were performed. Three different formulations of total lipid concentrations 60, 80, and 100 μmol/mL were used. Formulation with 60 μmol/mL total lipid (phosphatidylcholine from soybean and cholesterol from lanolin in 4 : 1, w/w) exhibited the highest rhodomyrtone encapsulation efficacy (65.47 ± 1.7%), average particle size (209.56 ± 4.8 nm), and ζ-potential (–41.19 ± 1.3 mV). All formulations demonstrated good stability when stored for 2 months in dark at 4°C as well as room temperature. Minimal inhibitory concentration and minimal bactericidal concentration values of liposomal formulation against 11 clinical bacterial isolates and reference strains ranged from 1 to 4 and from 4 to 64 μg/mL, respectively, while those of rhodomyrtone were 0.25–1 and 0.5–2 μg/mL, respectively. The MIC and MBC values of liposome formulation were more effective than topical drugs against Staphylococcus aureus and Staphylococcus epidermidis. PMID:23762104

  12. Liposomal encapsulated rhodomyrtone: a novel antiacne drug.

    PubMed

    Chorachoo, Julalak; Amnuaikit, Thanaporn; Voravuthikunchai, Supayang P

    2013-01-01

    Rhodomyrtone isolated from the leaves of Rhodomyrtus tomentosa possesses antibacterial, anti-inflammatory, and anti-oxidant activities. Since rhodomyrtone is insoluble in water, it is rather difficult to get to the target sites in human body. Liposome exhibited ability to entrap both hydrophilic and hydrophobic compounds and easily penetrate to the target site. The present study aimed to develop a novel liposomal encapsulated rhodomyrtone formulations. In addition, characterization of liposome, stability profiles, and their antiacne activity were performed. Three different formulations of total lipid concentrations 60, 80, and 100  μ mol/mL were used. Formulation with 60  μ mol/mL total lipid (phosphatidylcholine from soybean and cholesterol from lanolin in 4 : 1, w/w) exhibited the highest rhodomyrtone encapsulation efficacy (65.47 ± 1.7%), average particle size (209.56 ± 4.8 nm), and ζ -potential (-41.19 ± 1.3 mV). All formulations demonstrated good stability when stored for 2 months in dark at 4°C as well as room temperature. Minimal inhibitory concentration and minimal bactericidal concentration values of liposomal formulation against 11 clinical bacterial isolates and reference strains ranged from 1 to 4 and from 4 to 64  μ g/mL, respectively, while those of rhodomyrtone were 0.25-1 and 0.5-2  μ g/mL, respectively. The MIC and MBC values of liposome formulation were more effective than topical drugs against Staphylococcus aureus and Staphylococcus epidermidis.

  13. Liposomes as immune adjuvants: T cell dependence.

    PubMed

    Beatty, J D; Beatty, B G; Paraskevas, F; Froese, E

    1984-08-01

    The T cell dependence of the immune adjuvant action of liposomes containing the soluble antigens bovine serum albumin (BSA) and chicken immunoglobulin (CIgG) was studied with use of a quantitative enzyme-linked immunosorbent assay to measure serum antibody levels. Normal BALB/c mice, adult thymectomized mice, and congenitally athymic (nu+/nu+) mice were intravenously inoculated with liposomes containing BSA (Lip-BSA). The high levels of serum anti-BSA antibody that were seen in the normal group were decreased in the adult thymectomized group and were almost completely abrogated in the nu+/nu+ group. Reconstitution of nu+/nu+ mice with normal thymocytes and cortisone-resistant thymocytes led to a partial restoration of the anti-BSA antibody production after Lip-BSA immunization. Examination of the class of immunoglobulin produced in normal mice, immunized with Lip-BSA, showed an early low IgM response and a sustained higher IgG response that was primarily due to the IgG1 subclass. Trypsin removal of BSA exposed on the liposome surface decreased the resulting serum anti-BSA antibody level by 30% to 50%. Animals could be primed equally with a very low dose (0.2 micrograms) of Lip-BSA or with peritoneal macrophages that had phagocytosed the same dose of Lip-BSA. The adjuvant effect of liposomes containing CIgG on the number and type of specific anti-CIgG antibody-producing cells in the spleen was an early increase in IgM-producing cells followed by a substantially higher increase in IgG-producing cells. These observations suggest that liposome encapsulation of a soluble T-dependent antigen stimulates the helper T cell, not the suppressor T cell population, and that this stimulation involves uptake by macrophages.

  14. The potential of liposomes as dental drug delivery systems.

    PubMed

    Nguyen, Sanko; Hiorth, Marianne; Rykke, Morten; Smistad, Gro

    2011-01-01

    The potential of liposomes as a drug delivery system for use in the oral cavity has been investigated. Specifically targeting for the teeth, the in vitro adsorption of charged liposomal formulations to hydroxyapatite (HA), a common model substance for the dental enamel, has been conducted. The experiments were performed in human parotid saliva to simulate oral-like conditions. It was observed, however, that precipitation occurred in tubes containing DPPC/DPTAP or DPPC/DPPG-liposomes in parotid saliva with no HA present, indicating that constituents of parotid saliva reacted with the liposomes. The aggregation reactions of liposome-parotid saliva mixtures were examined by turbidimetry and by atomic force microscopy. Negatively charged DPPC/DPPS and DPPC/PI-liposomes were additionally included in these experiments. The initial turbidity of positive DPPC/DPTAP-liposomes in parotid saliva was very high, but decreased markedly after 30 min. AFM images showed large aggregates of micelle-like globules known to be present in saliva. The turbidity of the various negatively charged liposome and parotid saliva mixtures stayed relatively constant throughout the measuring time; however, their initial turbidities were different; mixtures with DPPC/DPPG-liposomes were the most turbid and DPPC/DPPA-liposomes the least. Pyrophosphate (PP) was added to the various liposome-parotid saliva mixtures to examine the effect of Ca(2+) on the interactions. The effect of PP treatment of the negatively charged liposome-parotid saliva mixtures was most pronounced with DPPC/DPPG-liposome mixtures where it caused a sudden drop in turbidity. For positive DPPC/DPTAP liposome and parotid saliva mixtures, the effect of PP was minimal. These experiments showed that saliva constituents may interact with liposomes. An appropriate liposomal drug delivery system intended for use in the oral cavity seems to be dependent on the liposomal formulation. Based on the present results, negatively charged DPPC/DPPA-liposomes

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

    PubMed Central

    Luo, Heng-Cong; Li, Na; Yan, Li; Mai, Kai-jin; Sun, Kan; Wang, Wei; Lao, Guo-Juan; Yang, Chuan; Zhang, Li-Ming; Ren, Meng

    2017-01-01

    Several biological barriers must be overcome to achieve efficient nonviral gene delivery. These barriers include target cell uptake, lysosomal degradation, and dissociation from the carrier. In this study, we compared the differences in the uptake mechanism of cationic, star-shaped polymer/MMP-9siRNA complexes (β-CD-(D3)7/MMP-9siRNA complexes: polyplexes) and commercial liposome/MMP-9siRNA complexes (Lipofectamine® 2000/MMP-9siRNA complexes: liposomes). The uptake pathway and transfection efficiency of the polyplexes and liposomes were determined by fluorescence microscopy, flow cytometry, and reverse transcriptase-polymerase chain reaction. The occurrence of intracellular processing was assessed by confocal laser scanning microscopy. Endosomal acidification inhibitors were used to explore the endosomal escape mechanisms of the polyplexes and lysosomes. We concluded that the polyplexes were internalized by non-caveolae- and non-clathrin-mediated pathways, with no lysosomal trafficking, thereby inducing successful transfection, while the majority of liposomes were internalized by clathrin-dependent endocytosis (CDE), caveolae-mediated endocytosis, and macropinocytosis, and only CDE induced successful transfection. Liposomes might escape more quickly than polyplexes, and the digestion effect of acidic organelles on liposomes was faint compared to the polyplexes, although both complexes escaped from endolysosomes via the proton sponge mechanism. This may be the key aspect that leads to the lower transfection efficiency of the β-CD-(D3)7/MMP-9siRNA complexes. The present study may offer some insights for the rational design of novel delivery systems with increased transfection efficiency but decreased toxicity. PMID:28223800

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

    PubMed

    Luo, Heng-Cong; Li, Na; Yan, Li; Mai, Kai-Jin; Sun, Kan; Wang, Wei; Lao, Guo-Juan; Yang, Chuan; Zhang, Li-Ming; Ren, Meng

    2017-01-01

    Several biological barriers must be overcome to achieve efficient nonviral gene delivery. These barriers include target cell uptake, lysosomal degradation, and dissociation from the carrier. In this study, we compared the differences in the uptake mechanism of cationic, star-shaped polymer/MMP-9siRNA complexes (β-CD-(D3)7/MMP-9siRNA complexes: polyplexes) and commercial liposome/MMP-9siRNA complexes (Lipofectamine(®) 2000/MMP-9siRNA complexes: liposomes). The uptake pathway and transfection efficiency of the polyplexes and liposomes were determined by fluorescence microscopy, flow cytometry, and reverse transcriptase-polymerase chain reaction. The occurrence of intracellular processing was assessed by confocal laser scanning microscopy. Endosomal acidification inhibitors were used to explore the endosomal escape mechanisms of the polyplexes and lysosomes. We concluded that the polyplexes were internalized by non-caveolae- and non-clathrin-mediated pathways, with no lysosomal trafficking, thereby inducing successful transfection, while the majority of liposomes were internalized by clathrin-dependent endocytosis (CDE), caveolae-mediated endocytosis, and macropinocytosis, and only CDE induced successful transfection. Liposomes might escape more quickly than polyplexes, and the digestion effect of acidic organelles on liposomes was faint compared to the polyplexes, although both complexes escaped from endolysosomes via the proton sponge mechanism. This may be the key aspect that leads to the lower transfection efficiency of the β-CD-(D3)7/MMP-9siRNA complexes. The present study may offer some insights for the rational design of novel delivery systems with increased transfection efficiency but decreased toxicity.

  17. Formulation of liposome for topical delivery of arbutin.

    PubMed

    Wen, Ai-Hua; Choi, Min-Koo; Kim, Dae-Duk

    2006-12-01

    The aims of this study were to encapsulate arbutin (AR) in liposome to enhance the skin-whitening activity, and to investigate the effect of liposome formulation on the entrapment efficiency (EE%), skin permeation rate and skin deposition. The liposomes were prepared by a film dispersion method with several different formulations and were separated from the solution by using the gel-filtration method. The physical (size distribution, morphology) and chemical (drug entrapment efficiency, hairless mouse skin permeation and deposition) properties of liposomes were characterized. The entrapment efficiency in all liposome formulations varied between 4.35% and 17.63%, and was dependent on the lipid content. The particle sizes of liposomes were in the range of 179.9-212.8 nm in all liposome formulations. Although the permeation rate of AR in the liposome formulations decreased compared with AR solution, the deposition amount of AR in the epidermis/dermis layers increased in AR liposomal formulation. These results suggest that liposomal formulation could enhance the skin deposition of hydrophilic skin-whitening agents, thereby enhancing their activities.

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

    PubMed Central

    Helm, Frieder; Fricker, Gert

    2015-01-01

    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. PMID:25835091

  19. Encapsulation enhancement and stabilization of insulin in cationic liposomes.

    PubMed

    Park, Se-Jin; Choi, Soon Gil; Davaa, Enkhzaya; Park, Jeong-Sook

    2011-08-30

    The purpose of this study was to enhance encapsulation efficiency and sustained-release delivery for parenteral administration of a protein drug. To reduce the administration frequency of protein drugs, it is necessary to develop sustained delivery systems. In this study, protein drug-loaded cationic liposomes were formulated with dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), dioleoyl-3-trimethylammonium-propane (DOTAP), and cholesterol (CH) at a molar ratio of DOPE/DOTAP/CH of 2/1.5/2. Five mol% of distearoylphosphatidyl ethanolamine polyethylene glycol (DSPE-PEG) was added prior to encapsulation of the drug into liposomes. Insulin was chosen as a model protein drug and encapsulation efficiency was evaluated in various liposomes with and without DSPE-PEG. Scanning electron microscopy was used to examine the insulin-loaded cationic liposomes. Structural analysis was performed using spectropolarimetry. Additionally, the stability and cytotoxicity of insulin-loaded cationic liposomes were evaluated. Liposomes coated with DSPE-PEG showed higher insulin encapsulation efficiency than did those without DSPE-PEG, but not significantly. Moreover, among the liposomes coated with DSPE-PEG, those hydrated with 10% sucrose showed higher encapsulation efficiency than did liposomes hydrated in either phosphate-buffered saline or 5% dextrose. In vitro release of insulin was prolonged by cationic liposomes. Our findings suggest that cationic liposomes may be a potential sustained-release delivery system for parenteral administration of protein and peptide drugs to prolong efficacy and improve bioavailability. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Bladder Uptake of Liposomes after Intravesical Administration Occurs by Endocytosis

    PubMed Central

    Rajaganapathy, Bharathi Raja; Chancellor, Michael B.; Nirmal, Jayabalan; Dang, Loan; Tyagi, Pradeep

    2015-01-01

    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. PMID:25811468

  1. Liposomes with polyribonucleotides as model of precellular systems

    NASA Astrophysics Data System (ADS)

    Baeza, Isabel; Ibañez, Miguel; Lazcano, Antonio; Santiago, Carlos; Arguello, Carlos; Wong, Carlos; Oró, J.

    1987-09-01

    A study of the encapsulation of poly(U) and poly(C) within liposomes made from dipalmitoylphosphatidyl choline (DPPC), from egg yold phosphatidyl choline (PC), and from PC with cholesterol (CHOL) was made. The liposomes were prepared under anoxic conditions following the reverse-phase evaporation method. Determinations showed that 36 to 70% of the available lipids form liposomes and 2 to 5% of the polyribonucleotides can be entrapped by liposomes. The encapsulation of polyribonucleotides has also been measured in the presence of urea, cyanamide and Zn++, condensing agents in prebiotic polymerization reactions. DPPC and PC:CHOL liposomes were formed in the presence of 1.0 M urea, although no PC liposomes were formed. The three types of liposomes were readily formed at 0.01 M urea, but in no case an enhancement of encapsulation efficiency of poly(U) was observed due to the presence of urea. Similar results were obtained with cyanamide. An enhanced encapsulation of poly(U) by the three types of liposomes was observed when Zn++ was in the range of 0.001 to 0.01 M. Poly(U) encapsulation was 15 to 25 times higher when liposomes were prepared from DPPC at 0.01 M Zn++. Similar results were obtained with poly(C). The advantages of DPPC-polyribonucleotide liposomes as precellular systems are discussed.

  2. Transformation of actin-encapsulating liposomes induced by cytochalasin D.

    PubMed Central

    Miyata, H; Kinosita, K

    1994-01-01

    Liposomes encapsulating actin filaments were prepared by swelling at 0 degrees C lipid film consisting of a mixture of dimyristoyl phosphatidylcholine and cardiolipin (equal amounts by weight) in 100 microM rabbit skeletal muscle actin and 0.5 mM CaCl2 followed by polymerization of actin at 30 degrees C. Liposomes initially assumed either disk or dumbbell shape, but when cytochalasin D was added to the medium surrounding the liposomes, they were found to become spindle shaped. Liposomes containing bovine serum albumin that were given cytochalasin D and actin-containing liposomes that were given dimethylformamide, the solvent for cytochalasin D, did not transform. These results indicated actin-cytochalasin interaction is involved in the transformation process. Falling-ball viscometry and sedimentation analysis of actin solution indicated that cytochalasin cleaved actin filaments and caused depolymerization. The observation of polarized fluorescence of encapsulated actin labeled with acrylodan indicated that the actin filaments in the transformed liposomes aligned along the long axis of the liposomes. Because the actin filaments in the disk- or dumbbell-shaped liposomes formed bundles running along the liposome contour, the transformation was likely to be accompanied by the change in the actin filament arrangement in the liposomes, which was induced by actin-cytochalasin interaction. Images FIGURE 1 FIGURE 2 FIGURE 3 PMID:7948706

  3. Liposome disposition in vivo. VI: Delivery to the lung

    SciTech Connect

    Abra, R.M.; Hunt, C.A.; Lau, D.T.

    1984-02-01

    The effect of negatively charged liposome components and vesicle size on the time course and dose dependency of liposome disposition in mice was studied with a view to optimizing liposome delivery to the lung. The disposition of large multilamellar liposomes was followed using 125I-labeled p-hydroxybenzamidine phosphatidyl ethanolamine. Of the three negatively charged liposome compositions studied (phosphatidyl choline-X-cholesterol-alpha-tocopherol, molar ratio: 4:1:5:0.1; X . phosphatidyl serine, dipalmitoyl phosphatidic acid, or phosphatidyl glycerol), phosphatidyl serine liposomes resulted in the greatest accumulation in lungs. Lung levels decreased up to 95 h postdose, at which time 6% of the liposome dose present at 2 h still remained. The disposition of phosphatidyl serine-containing liposomes was independent of dose for the range 0.04-21 mumol/animal. When liposomes containing phosphatidyl choline were prepared using a variety of extrusion and dialysis conditions, a strong link between liposome size and lung accumulation was revealed. A maximum lung accumulation of 30.9% of the administered dose was achieved with no detectable gross pathological lung lesions up to 24 h postdose.

  4. Internalization of paramagnetic phosphatidylserine-containing liposomes by macrophages.

    PubMed

    Geelen, Tessa; Yeo, Sin Yuin; Paulis, Leonie E M; Starmans, Lucas W E; Nicolay, Klaas; Strijkers, Gustav J

    2012-08-28

    Inflammation plays an important role in many pathologies, including cardiovascular diseases, neurological conditions and oncology, and is considered an important predictor for disease progression and outcome. In vivo imaging of inflammatory cells will improve diagnosis and provide a read-out for therapy efficacy. Paramagnetic phosphatidylserine (PS)-containing liposomes were developed for magnetic resonance imaging (MRI) and confocal microscopy imaging of macrophages. These nanoparticles also provide a platform to combine imaging with targeted drug delivery. Incorporation of PS into liposomes did not affect liposomal size and morphology up to 12 mol% of PS. Liposomes containing 6 mol% of PS showed the highest uptake by murine macrophages, while only minor uptake was observed in endothelial cells. Uptake of liposomes containing 6 mol% of PS was dependent on the presence of Ca2+ and Mg2+. Furthermore, these 6 mol% PS-containing liposomes were mainly internalized into macrophages, whereas liposomes without PS only bound to the macrophage cell membrane. Paramagnetic liposomes containing 6 mol% of PS for MR imaging of macrophages have been developed. In vitro these liposomes showed specific internalization by macrophages. Therefore, these liposomes might be suitable for in vivo visualization of macrophage content and for (visualization of) targeted drug delivery to inflammatory cells.

  5. Internalization of paramagnetic phosphatidylserine-containing liposomes by macrophages

    PubMed Central

    2012-01-01

    Background Inflammation plays an important role in many pathologies, including cardiovascular diseases, neurological conditions and oncology, and is considered an important predictor for disease progression and outcome. In vivo imaging of inflammatory cells will improve diagnosis and provide a read-out for therapy efficacy. Paramagnetic phosphatidylserine (PS)-containing liposomes were developed for magnetic resonance imaging (MRI) and confocal microscopy imaging of macrophages. These nanoparticles also provide a platform to combine imaging with targeted drug delivery. Results Incorporation of PS into liposomes did not affect liposomal size and morphology up to 12 mol% of PS. Liposomes containing 6 mol% of PS showed the highest uptake by murine macrophages, while only minor uptake was observed in endothelial cells. Uptake of liposomes containing 6 mol% of PS was dependent on the presence of Ca2+ and Mg2+. Furthermore, these 6 mol% PS-containing liposomes were mainly internalized into macrophages, whereas liposomes without PS only bound to the macrophage cell membrane. Conclusions Paramagnetic liposomes containing 6 mol% of PS for MR imaging of macrophages have been developed. In vitro these liposomes showed specific internalization by macrophages. Therefore, these liposomes might be suitable for in vivo visualization of macrophage content and for (visualization of) targeted drug delivery to inflammatory cells. PMID:22929153

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

    PubMed

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

    2011-05-01

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

  7. Co-Encapsulating the Fusogenic Peptide INF7 and Molecular Imaging Probes in Liposomes Increases Intracellular Signal and Probe Retention

    PubMed Central

    Martin, Erik W.; Li, Changqing; Lu, Wuyuan; Kao, Joseph P. Y.

    2015-01-01

    Liposomes are promising vehicles to deliver diagnostic and therapeutic agents to cells in vivo. After uptake into cells by endocytosis, liposomes are degraded in the endolysosomal system. Consequently, the encapsulated cargo molecules frequently remain sequestered in endosomal compartments; this limits their usefulness in many applications (e.g. gene delivery). To overcome this, various fusogenic peptides have been developed to facilitate delivery of liposomally-encapsulated molecules into the cytosol. One such peptide is the pH-sensitive influenza-derived peptide INF7. Liposomal delivery of imaging agents is an attractive approach for enabling cell imaging and cell tracking in vivo, but can be hampered by inadequate intracellular accumulation and retention of probes caused by exocytosis (and possible degradation) of endosome-entrapped probes. Such signal loss could be minimized by facilitating escape of probe molecules from endolysosomal compartments into the cytosol. We investigated the ability of co-encapsulated INF7 to release liposomally-delivered rhodamine fluorophores into the cytosol after endosomal acidification/maturation. We co-encapsulated INF7 and fluorescent rhodamine derivatives having vastly different transport properties to show that after endocytosis by CV1 cells, the INF7 peptide is activated by acidic endosomal pH and facilitates efficient release of the fluorescent tracers into the cytosol. Furthermore, we show that INF7-facilitated escape from endosomes markedly enhanced retention of tracers that cannot be actively extruded from the cytosol. Minimizing loss of intracellular probes improves cellular imaging by increasing the signal-to-noise ratio of images and lengthening the time window that imaging can be performed. In particular, this will enhance in vivo electron paramagnetic resonance imaging, an emergent magnetic resonance imaging modality requires exogenous paramagnetic imaging agents and is highly promising for cellular and molecular

  8. Preparation and evaluation of liposomal formulations of tropicamide for ocular delivery.

    PubMed

    Nagarsenker, M S; Londhe, V Y; Nadkarni, G D

    1999-11-10

    Tropicamide, a mydriatic, cycloplegic drug was entrapped in liposomes. Liposomes were investigated by laser counting studies, transmission electron microscopy and differential scanning calorimetry for characterization. The precorneal clearance of liposomes was compared with solution by gamma-scintigraphy in the rabbit. The neutral liposomes failed to demonstrate significant enhancement in precorneal retention in comparison with aqueous solution. The potential of liposomes as an ophthalmic drug delivery system was investigated by comparing pupil dilatory effect of tropicamide by topical instillation, in the rabbit eye, of the solution and various drug-loaded liposomal forms, i.e. neutral liposomes, positively charged liposomes and neutral liposomes dispersed in 0.25% (w/v) polycarbophil gel. The positively charged liposomal formulation and liposomes dispersed in polycarbophil gel were found to be more effective than neutral liposomal dispersion when data were statistically treated at the 5% level of significance.

  9. The effect of lipid composition and liposome size on the release properties of liposomes-in-hydrogel.

    PubMed

    Hurler, Julia; Žakelj, Simon; Mravljak, Janez; Pajk, Stane; Kristl, Albin; Schubert, Rolf; Škalko-Basnet, Nataša

    2013-11-01

    To study the release of liposome-associated drugs into hydrogels, we designed and synthesized two pH-sensitive rhodamine derivatives to use as model compounds of different lipophilicities. The dyes were fluorescent when in the free form released from liposomes into the chitosan hydrogel, but not when incorporated within liposomes. The effect of liposomal composition, surface charge and vesicle size on the release of those incorporated dyes was evaluated. The lipophilicity of the rhodamine derivatives affected both the amount and rate of release. While liposome size had only a minor effect on the release of dyes into the hydrogel, the surface charge affected the release to a greater extent. By optimizing the characteristics of liposomes we could develop a liposomes-in-hydrogel system for application in wound therapy. We further characterized liposomes-in-hydrogel for their rheological properties, textures and moisture handling, as well as their potential to achieve a controlled release of the dye. The polymer-dependent changes in the hydrogel properties were observed upon addition of liposomes. The charged liposomes exhibited stronger effects on the textures of the chitosan hydrogels than the neutral ones. In respect to the ability of the system to handle wound exudates, chitosan-based hydrogels were found to be superior to Carbopol-based hydrogels.

  10. Preparation, characterization, cytotoxicity and pharmacokinetics of liposomes containing lipophilic gemcitabine prodrugs.

    PubMed

    Immordino, Maria Laura; Brusa, Paola; Rocco, Flavio; Arpicco, Silvia; Ceruti, Maurizio; Cattel, Luigi

    2004-12-10

    Gemcitabine is a known anticancer agent rapidly deaminated to the inactive metabolite 2',2'-difluorodeoxyuridine; it must therefore be administered at very high dose. Many different approaches have been tried to improve the metabolic stability; we synthesized a series of increasingly lipophilic prodrugs of gemcitabine by linking the 4-amino group with valeroyl, heptanoyl, lauroyl and stearoyl linear acyl derivatives. We studied their stability at storage, in plasma and with the lysosomal intracellular enzyme cathepsins. We studied incorporation of these lipophilic prodrugs in liposomes, where their encapsulation efficiency (EE) closely depends on the length of the saturated 4-(N)-acyl chain, the phospholipids chosen and the presence of cholesterol. A maximum EE of 98% was determined for 4-(N)-stearoyl-gemcitabine incorporated in DSPC/DSPG 9:1. This formulation was correlated with the highest stability in vitro and in vivo. Cytotoxicity of gemcitabine prodrugs, free or encapsulated in liposomes, was between two- and sevenfold that of free gemcitabine. Encapsulation of long-chain lipophilic prodrugs of gemcitabine in liposomes protected the drug from degradation in plasma, assuring a long plasma half-time and intracellular release of the free drug.

  11. Liposomal amphotericin B for the treatment of visceral leishmaniasis.

    PubMed

    Bern, Caryn; Adler-Moore, Jill; Berenguer, Juan; Boelaert, Marleen; den Boer, Margriet; Davidson, Robert N; Figueras, Concepcion; Gradoni, Luigi; Kafetzis, Dimitris A; Ritmeijer, Koert; Rosenthal, Eric; Royce, Catherine; Russo, Rosario; Sundar, Shyam; Alvar, Jorge

    2006-10-01

    During the past decade, liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL). The World Health Organization convened a workshop to review current knowledge and to develop guidelines for liposomal amphotericin B use for VL. In Europe, liposomal amphotericin B is widely used to treat VL. In Africa and Asia, the VL disease burden is high and drug access is poor; liposomal amphotericin B is available only through preferential pricing for nonprofit groups in East Africa. Clinical trials and experience demonstrate high efficacy and low toxicity for liposomal amphotericin B (total dose, 20 mg/kg) in immunocompetent patients with VL. Combination trials in areas with antileishmanial drug resistance, and treatment and secondary prophylaxis trials in VL-human immunodeficiency virus-coinfected patients, are important to safeguard the current armamentarium and to optimize regimens. The public health community should work to broaden access to preferential liposomal amphotericin B pricing by public sector VL treatment programs.

  12. Advances and Challenges of Liposome Assisted Drug Delivery

    PubMed Central

    Sercombe, Lisa; Veerati, Tejaswi; Moheimani, Fatemeh; Wu, Sherry Y.; Sood, Anil K.; Hua, Susan

    2015-01-01

    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. PMID:26648870

  13. Recent advances in liposome surface modification for oral drug delivery.

    PubMed

    Nguyen, Thanh Xuan; Huang, Lin; Gauthier, Mario; Yang, Guang; Wang, Qun

    2016-05-01

    Oral delivery via the gastrointestinal (GI) tract is the dominant route for drug administration. Orally delivered liposomal carriers can enhance drug solubility and protect the encapsulated theraputic agents from the extreme conditions found in the GI tract. Liposomes, with their fluid lipid bilayer membrane and their nanoscale size, can significantly improve oral absorption. Unfortunately, the clinical applications of conventional liposomes have been hindered due to their poor stability and availability under the harsh conditions typically presented in the GI tract. To overcome this problem, the surface modification of liposomes has been investigated. Although liposome surface modification has been extensively studied for oral drug delivery, no review exists so far that adequately covers this topic. The purpose of this paper is to summarize and critically analyze emerging trends in liposome surface modification for oral drug delivery.

  14. High performance optical resolution with liposome immobilized hydrogel.

    PubMed

    Ishigami, Takaaki; Sugita, Kazuma; Suga, Keishi; Okamoto, Yukihiro; Umakoshi, Hiroshi

    2015-12-01

    We prepared liposome immobilized hydrogels (LI-gels) for analysis and separation of chiral molecules, to overcome the drawbacks of liposomes such as low stability, and difficulties with handling and isolation from sample solutions. The amounts of liposomes in the hydrogels were larger than those in other solid matrices reported previously. The liposome morphology was intact, and its original properties, such as fluidity and phase transition behaviors, were preserved. We investigated the chiral recognition performance of the LI-gel, as described in our previous paper. Our results indicate that the enantioselectivity of the LI-gel was higher than those of conventional methods and of the liposomes alone. Our prepared LI-gel therefore overcomes the drawbacks of liposomes, and has potential applications in analysis and separation, including chiral separation.

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

    SciTech Connect

    Hawthorne, M. Frederick

    2005-04-07

    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. Use of Liposomes for Directed Drug Delivery Against Entamoeba Histolytica

    DTIC Science & Technology

    1990-01-20

    Classification) Use of Liposomes for Directed Drug Delivery Against Entamoeba histolytica 12. PERSONAL AUTHOR(S) Gordon B. Bailey, Ph.D., Professor of...Liposomes, Entamoeba histolytica , DrugsGlycosphingolipids, 09 03 I Phagocytosis, Lipids. Actin, A ,- 19. ABSTRAC(Continue on reverse if necessary and...identify by block number) The ability of purified glycosphingolipids to enhance liposome stimulated Entamoeba histolytica actin polymerization was

  17. Liposome clusters with shear stress-induced membrane permeability.

    PubMed

    Yoshimoto, Makoto; Tamura, Ryota; Natsume, Tomotaka

    2013-09-01

    Clusters of negatively charged liposomes were prepared by the addition of Ca(2+) and characterized in their structure and membrane permeability under shear stress. The liposomes mainly used were composed of zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 20 mol% negatively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) and 30 mol% cholesterol. The liposomes with mean diameter of 193 nm were aggregated into the clusters with a distribution peak at about 1.5 μm in the 50mM Tris buffer solution of pH 8.5 at the lipid and Ca(2+) concentrations of 1.0mM and 40 mM, respectively. More than 90% of liposomes were redispersed at the Ca(2+) concentration of 80 mM. POPG-rich liposomes (POPC/POPG/cholesterol=5:65:30 [lipid]=1.0mM) were irreversibly aggregated at [Ca(2+)]≥ 10 mM, indicating the significant contribution of POPC to the reversible clustering of liposomes. The membranes of liposome clusters were impermeable to 5(6)-carboxyfluorescein (CF) in the static liquid system at 25°C due to the decrease in specific surface area of the liposomal system. In the shear flow, in clear contrast, continuous membrane permeation of CF was observed at the shear rate of 1.5 × 10(3)s(-1), exhibiting comparable membrane permeability to the non-clustered liposomes. The theoretical analysis of modified DLVO potential indicated that liposome membranes were not in contact with each other within the clusters. Therefore, the liposome clusters are structurally flexible under the applied shear stress, providing sufficient lipid membrane-water interfacial area for the permeation of CF. The results obtained would be important to control the formation of liposome clusters and their permeabilization for biochemical and biomedical applications.

  18. Microfluidic synthesis of multifunctional liposomes for tumour targeting.

    PubMed

    Ran, Rui; Middelberg, Anton P J; Zhao, Chun-Xia

    2016-12-01

    Nanotechnology has started a new era in engineering multifunctional nanoparticles for diagnosis and therapeutics by incorporating therapeutic drugs, targeting ligands, stimuli-responsive release and imaging molecules. However, more functionality requires more complex synthesis processes, resulting in poor reproducibility, low yield and high production cost, hence difficulties in clinical translation. Herein we report a one-step microfluidic method for making multifunctional liposomes. Three formulations were prepared using this simple method, including plain liposomes, PEGylated liposomes and folic acid functionalised liposomes, all with a fluorescence dye encapsulated for imaging. The size and surface properties of these liposomes can be precisely controlled by simply tuning the flow rate ratio and the ratio of the lipids to PEGylated lipid (DSPE-PEG2000) and to the DSPE-PEG2000-Folate, respectively. The synthesised liposomes remained stable under mimic serum conditions. Compared to the plain liposomes and PEGylated liposomes, the targeted folic acid functionalised liposomes exhibited enhanced cellular uptake by the FA receptor positive SKOV3 cells, but not the negative MCF7 cells, and this enhanced uptake could be inhibited by adding excess free folic acid, indicating high specificity of FA ligand-receptor endocytosis. Further evaluation using the 3D tumour spheroid model also showed higher internalisation of the targeted liposome formulation in comparison with the PEGylated one. To the best of our knowledge, this work demonstrates for the first time the versatility of this microfluidic method for making different liposome formulations in a single step, their superior physicochemical properties as well as the enhanced cellular uptake and tumour spheroid uptake of the targeted liposomes.

  19. Preparation and in vitro activity of liposome encapsulated opioids.

    PubMed

    Reig, F; Alsina, M A; Busquets, M A; Valencia, G; Garcia Anton, J M

    1989-01-01

    Four opiate molecules: morphine, naloxone, meperidine and codeine have been encapsulated in liposomes. The encapsulation efficiency has been studied as a function of the following parameters: liposome preparation method, lipid composition and opioid molecule hydrophobicity. The most important parameter as far as the entrapment efficiency is concerned is the liposome preparation method. The opioid activity of these molecules in vitro (Guinea Pig Ileum preparation) has been determined. No differences in the IC50 values could be found between encapsulated and free drug molecules.

  20. In vivo analysis of biodegradable liposome gold nanoparticles as efficient agents for photothermal therapy of cancer.

    PubMed

    Rengan, Aravind Kumar; Bukhari, Amirali B; Pradhan, Arpan; Malhotra, Renu; Banerjee, Rinti; Srivastava, Rohit; De, Abhijit

    2015-02-11

    We report biodegradable plasmon resonant liposome gold nanoparticles (LiposAu NPs) capable of killing cancer cells through photothermal therapy. The pharmacokinetic study of LiposAu NPs performed in a small animal model indicates in situ degradation in hepatocytes and further getting cleared through the hepato-biliary and renal route. Further, the therapeutic potential of LiposAu NPs tested in mouse tumor xenograft model using NIR laser (750 nm) illumination resulted in complete ablation of the tumor mass, thus prolonging disease-free survival.

  1. Small unilamellar liposomes as a membrane model for cell inactivation by cold atmospheric plasma treatment

    NASA Astrophysics Data System (ADS)

    Maheux, S.; Frache, G.; Thomann, J. S.; Clément, F.; Penny, C.; Belmonte, T.; Duday, D.

    2016-09-01

    Cold atmospheric plasma is thought to be a promising tool for numerous biomedical applications due to its ability to generate a large diversity of reactive species in a controlled way. In some cases, it can also generate pulsed electric fields at the zone of treatment, which can induce processes such as electroporation in cell membranes. However, the interaction of these reactive species and the pulse electric field with cells in a physiological medium is very complex, and we still need a better understanding in order to be useful for future applications. A way to reach this goal is to work with model cell membranes such as liposomes, with the simplest physiological liquid and in a controlled atmosphere in order to limit the number of parallel reactions and processes. In this paper, where this approach has been chosen, 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC) small unilamellar vesicles (SUV) have been synthesized in a phosphate buffered aqueous solution, and this solution has been treated by a nanosecond pulsed plasma jet under a pure nitrogen atmosphere. It is only the composition of the plasma gas that has been changed in order to generate different cocktails of reactive species. After the quantification of the main plasma reactive species in the phosphate buffered saline (PBS) solution, structural, surface charge state, and chemical modifications generated on the plasma treated liposomes, due to the interaction with the plasma reactive species, have been carefully characterized. These results allow us to further understand the effect of plasma reactive species on model cell membranes in physiological liquids. The permeation through the liposomal membrane and the reaction of plasma reactive species with molecules encapsulated inside the liposomes have also been evaluated. New processes of degradation are finally presented and discussed, which come from the specific conditions of plasma treatment under the pure nitrogen atmosphere.

  2. The preparation and characterization of gas bubble containing liposomes.

    PubMed

    Liu, Rui; Wei, Xiaohui; Yao, Yanbin; Chai, Qiliang; Chen, Yue; Xu, Yuhong

    2005-01-01

    Liposomes and lipid nano-particles containing gas bubbles have great potentials to be used as ultrasound contrast agents or as drug and gene delivery vehicles. We developed a method to enable in situ CO2gas bubbles formation inside liposomes. The resulted bubbles containing liposomes were shown to be able to effectively echo ultrasound. Their acoustic properties were assessed by ultrasound imaging and intensity analysis. Compared to most other echogenic liposome formulations reported, our method is easier, faster, and more economical. It would be useful for many applications with improvements and optimization.

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

    PubMed

    Jain, Pritesh P; Leber, Regina; Nagaraj, Chandran; Leitinger, Gerd; Lehofer, Bernhard; Olschewski, Horst; Olschewski, Andrea; Prassl, Ruth; Marsh, Leigh M

    2014-01-01

    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 similar pharmacologic efficacy as nonencapsulated iloprost. Cationic liposomes can encapsulate iloprost with high efficacy and can serve as potential iloprost carriers to improve its therapeutic efficacy.

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

    PubMed Central

    Jain, Pritesh P; Leber, Regina; Nagaraj, Chandran; Leitinger, Gerd; Lehofer, Bernhard; Olschewski, Horst; Olschewski, Andrea; Prassl, Ruth; Marsh, Leigh M

    2014-01-01

    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 similar pharmacologic efficacy as nonencapsulated iloprost. Cationic liposomes can encapsulate iloprost with high efficacy and can serve as potential iloprost carriers to improve its therapeutic efficacy. PMID:25045260

  5. Application of long-circulating liposomes to cancer photodynamic therapy.

    PubMed

    Oku, N; Saito, N; Namba, Y; Tsukada, H; Dolphin, D; Okada, S

    1997-06-01

    Photodynamic therapy (PDT) as a cancer treatment is notable for its quite low side effects in comparison with those of chemotherapy and radiotherapy. However, the accumulation of porphyrin derivatives used in PDT into tumor tissues is rather low. Since long-circulating liposomes are known to accumulate passively into tumor tissues, we liposomalized a porphyrin derivative, benzoporphyrin derivative monoacid ring A (BPD-MA), and used these liposomes to investigate the usefulness of PDT for tumor-bearing mice. BPD-MA was liposomalized into glucuronate-modified liposomes, which are known to be long-circulating. These liposomes were injected i.v. into Balb/c mice bearing Meth A sarcoma, and tumor regression and survival time were monitored after irradiation with laser light. Tumor regression and complete curing of tumor (80% cure rate by the treatment with 6 mg/kg BPD-MA) were observed when long circulating liposomalized BPD-MA was injected and laser-irradiated. In contrast, only a 20% cure rate was obtained when the animals were treated with BPD-MA solution or BPD-MA entrapped in conventional liposomes. These results suggest that a long-circulating liposomal formulation of photo-sensitive agents is useful for PDT.

  6. Liposomally encapsulated diclofenac for sonophoresis induced systemic delivery.

    PubMed

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

    1995-01-01

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

  7. Elastic liposomes containing benzophenone-3 for sun protection factor enhancement.

    PubMed

    Severino, Patrícia; Moraes, Lívia Faria; Zanchetta, Beatriz; Souto, Eliana B; Santana, Maria H A

    2012-01-01

    This work was focused on the loading of benzophenone-3 in elastic liposomes composed of egg phosphatidylcholine and cholesterol, prepared by the Bangham method. Samples were characterized in terms of particle size, polydispersity index (PI), zeta potential, encapsulation efficiency and in vitro photoprotection properties. The extrusion of liposomes loading benzophenone-3 produced reduced-size (100 nm) elastic liposomes with a PI of 0.2. The active was loaded with a concentration of 20.34% (m/m) revealing changes in the ultraviolet properties after loading. On the basis of these results, it can be anticipated that liposomes are able to improve sun protector factor in vitro compared the free active.

  8. Liposomal forms of rhenium cluster compounds: enhancement of biological activity.

    PubMed

    Shtemenko, Natalia I; Zabitskaya, Elena D; Berzenina, Oksana V; Yegorova, Dina E; Shtemenko, Alexander V

    2008-08-01

    Liposomal formulations of dinuclear cluster rhenium (Re) compounds were used in biochemical trials. Interaction of liposomal forms of some Re compounds with red blood cells in experiments in vitro showed strong cell-stabilizing properties. In the models of tumor growth and hemolytic anemia in vivo, liposomal forms had better therapeutic effects in comparison with their solutions. The process of formation of liposomes of cluster Re compounds with different organic ligands was investigated by the method of electronic absorption spectra and mechanism of their interactions with lipids is proposed. Encapsulation of cluster Re compounds to lipid coating may have activation significance for the quadruple Re-Re bond.

  9. Liposomes and MTT cell viability assay: an incompatible affair.

    PubMed

    Angius, Fabrizio; Floris, Alice

    2015-03-01

    The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay is commonly used to evaluate the cytotoxicity potential of drugs vehicled by liposomes. However, liposome delivering drugs could produce inconsistent values of MTT absorbance. On the basis of previous experiments demonstrating the MTT affinity for lipid droplets, this paper aims to show that empty-liposomes interfere, per se, on MTT assay due to its lipidic nature. This brings into question the use of MTT testing cytotoxicity when liposomes are involved in delivering drugs.

  10. Complexation-triggerable liposome mixed with silk protein and chitosan.

    PubMed

    Hong, Yeon-Ji; Kim, Jin-Chul

    2015-01-01

    Complexation-triggerable liposomes were prepared by modifying the surface of egg phosphatidylcholine (EPC) liposomes with hydrophobicized silk fibroin (HmSF) and hydrophobicized chitosan (HmCh). Maximum complexation, determined by measuring the diameter of complexation, was found when the ratio of HmSF to HmCh was 14:1, so they were immobilized on the surface of liposomes at the same ratio. The degree of fluorescence quenching of calcein in liposomal suspension was as high as 68% when the ratio of surface modifier (HmSF + HmCh) to EPC was 1:15. When the ratio was increased to 1:5, the degree of quenching decreased to 32%, indicating the inefficient formation of liposome. Liposome mixed with the surface modifier was multi-lamellar vesicle on TEM photo. And, the mean diameter was larger than those of liposome mixed with either HmSF or HmCh, possibly due to insoluble complex on the liposomal surface. The liposome exhibited a pH-sensitive release and triggered the release at pH 5.5 and 6.0. It is believed that complexation is responsible for the promoted release at those pH values.

  11. Distribution of local anesthetics between aqueous and liposome phases.

    PubMed

    Ruokonen, Suvi-Katriina; Duša, Filip; Rantamäki, Antti H; Robciuc, Alexandra; Holma, Paula; Holopainen, Juha M; Abdel-Rehim, Mohamed; Wiedmer, Susanne K

    2017-01-06

    Liposomes were used as biomimetic models in capillary electrokinetic chromatography (EKC) for the determination of distribution constants (KD) of certain local anesthetics and a commonly used preservative. Synthetic liposomes comprised phosphatidylcholine and phosphatidylglycerol phospholipids with and without cholesterol. In addition, ghost liposomes made from red blood cell (RBC) lipid extracts were used as pseudostationary phase to acquire information on how the liposome composition affects the interactions between anesthetics and liposomes. These results were compared with theoretical distribution coefficients at pH 7.4. In addition to 25°C, the distribution constants were determined at 37 and 42°C to simulate physiological conditions. Moreover, the usability of five electroosmotic flow markers in liposome (LEKC) and micellar EKC (MEKC) was studied. LEKC was proven to be a convenient and fast technique for obtaining data about the distribution constants of local anesthetics between liposome and aqueous phase. RBC liposomes can be utilized for more representative model of cellular membranes, and the results indicate that the distribution constants of the anesthetics are greatly dependent on the used liposome composition and the amount of cholesterol, while the effect of temperature on the distribution constants is less significant.

  12. Preparation and evaluation of liposome-encapsulated codrug LMX.

    PubMed

    Zhong, Yan; Wang, Jing; Wang, Yao; Wu, Bin

    2012-11-15

    A novel codrug (LMX) consisting of Lamivudine and Ursolic acid has been shown to possess the dual action of anti-hepatitis B virus activity and hepatoprotective effects against acute liver injury in vivo. Because of the limited water solubility of LMX, our aims were to design and optimize a liposomal formulation that could facilitate its in vivo administration, and to estimate the potential of LMX-loaded liposomes as oral or intravenous delivery system. In this work, LMX-loaded liposomes were prepared by the thin film hydration method coupled with sonication. LMX-loaded liposomes showed spherical morphology under transmission electron microscope (TEM) analysis. The mean particle size of liposomes was about 210 nm, and the drug entrapment efficiency was more than 90%. Stability data indicated that lyophilized liposomes were stable for at least 6 months at 4 °C. In vitro drug release profile of LMX-loaded liposomes showed a sustained release profile of LMX and an initial mild burst was observed. The relative bioavailability of LMX-loaded liposomes was 1074.8% compared with LMX suspension after oral administration, and 135.2% relative to 50% alcohol solution after intravenous (i.v.) administration. These results indicated that LMX-loaded liposomes were valued to develop as a practical preparation for oral or i.v. administration. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Current trends in the use of liposomes for tumor targeting

    PubMed Central

    Deshpande, Pranali P; Biswas, Swati; Torchilin, Vladimir P

    2013-01-01

    The use of liposomes for drug delivery began early in the history of pharmaceutical nanocarriers. These nanosized, lipid bilayered vesicles have become popular as drug delivery systems owing to their efficiency, biocompatibility, nonimmunogenicity, enhanced solubility of chemotherapeutic agents and their ability to encapsulate a wide array of drugs. Passive and ligand-mediated active targeting promote tumor specificity with diminished adverse off-target effects. The current field of liposomes focuses on both clinical and diagnostic applications. Recent efforts have concentrated on the development of multifunctional liposomes that target cells and cellular organelles with a single delivery system. This review discusses the recent advances in liposome research in tumor targeting. PMID:23914966

  14. Liposomes in tissue engineering and regenerative medicine

    PubMed Central

    Monteiro, Nelson; Martins, Albino; Reis, Rui L.; Neves, Nuno M.

    2014-01-01

    Liposomes are vesicular structures made of lipids that are formed in aqueous solutions. Structurally, they resemble the lipid membrane of living cells. Therefore, they have been widely investigated, since the 1960s, as models to study the cell membrane, and as carriers for protection and/or delivery of bioactive agents. They have been used in different areas of research including vaccines, imaging, applications in cosmetics and tissue engineering. Tissue engineering is defined as a strategy for promoting the regeneration of tissues for the human body. This strategy may involve the coordinated application of defined cell types with structured biomaterial scaffolds to produce living structures. To create a new tissue, based on this strategy, a controlled stimulation of cultured cells is needed, through a systematic combination of bioactive agents and mechanical signals. In this review, we highlight the potential role of liposomes as a platform for the sustained and local delivery of bioactive agents for tissue engineering and regenerative medicine approaches. PMID:25401172

  15. Studying mechanosensitive ion channels using liposomes.

    PubMed

    Martinac, Boris; Rohde, Paul R; Battle, Andrew R; Petrov, Evgeny; Pal, Prithwish; Foo, Alexander Fook; Vásquez, Valeria; Huynh, Thuan; Kloda, Anna

    2010-01-01

    Mechanosensitive (MS) ion channels are the primary molecular transducers of mechanical force into electrical and/or chemical intracellular signals in living cells. They have been implicated in innumerable mechanosensory physiological processes including touch and pain sensation, hearing, blood pressure control, micturition, cell volume regulation, tissue growth, or cellular turgor control. Much of what we know about the basic physical principles underlying the conversion of mechanical force acting upon membranes of living cells into conformational changes of MS channels comes from studies of MS channels reconstituted into artificial liposomes. Using bacterial MS channels as a model, we have shown by reconstituting these channels into liposomes that there is a close relationship between the physico-chemical properties of the lipid bilayer and structural dynamics bringing about the function of these channels.

  16. Effect of liposomal fluidity on skin permeation of sodium fluorescein entrapped in liposomes

    PubMed Central

    Subongkot, Thirapit; Ngawhirunpat, Tanasait

    2015-01-01

    The purpose of this study was to investigate the effect of ultradeformable liposome components, Tween 20 and terpenes, on vesicle fluidity. The fluidity was evaluated by electron spin resonance spectroscopy using 5-doxyl stearic acid and 16-doxyl stearic acid as spin labels for phospholipid bilayer fluidity at the C5 atom of the acyl chain near the polar head group (hydrophilic region) and the C16 atom of the acyl chain (lipophilic region), respectively. The electron spin resonance study revealed that Tween 20 increased the fluidity at the C5 atom of the acyl chain, whereas terpenes increased the fluidity at the C16 atom of the acyl chain of the phospholipid bilayer. The increase in liposomal fluidity resulted in the increased skin penetration of sodium fluorescein. Confocal laser scanning microscopy showed that ultradeformable liposomes with terpenes increase the skin penetration of sodium fluorescein by enhancing hair follicle penetration. PMID:26229462

  17. Liposomes as lubricants: beyond drug delivery.

    PubMed

    Goldberg, Ronit; Klein, Jacob

    2012-05-01

    In this paper we review recent work (Goldberg et al., 2011a,b) on a new use for phosphatidylcholine liposomes: as ultra-efficient boundary lubricants at up to the highest physiological pressures. Using a surface force balance, we have measured the normal and shear interactions as a function of surface separation between layers of hydrogenated soy phophatidylcholine (HSPC) small unilamellar vesicles (SUVs) adsorbed from dispersion, at both pure water and physiologically high salt concentrations of 0.15 M NaNO(3). Cryo-Scanning Electron Microscopy shows each surface to be coated by a close-packed HSPC-SUV layer with an over-layer of liposomes on top. The shear forces reveal strikingly low friction coefficients down to 2×10(-5) in pure water system or 6×10(-4) in the 150 mM salt system, up to contact pressures of at least 12 MPa (pure water) or 6 MPa (high salt), comparable with those in the major joints. This low friction is attributed to the hydration lubrication mechanism arising from rubbing of the highly hydrated phosphocholine-headgroup layers exposed at the outer surface of each liposome, and provides support for the conjecture that phospholipids may play a significant role in biological lubrication.

  18. Phototriggerable Liposomes: Current Research and Future Perspectives

    PubMed Central

    Puri, Anu

    2013-01-01

    The field of cancer nanomedicine is considered a promising area for improved delivery of bioactive molecules including drugs, pharmaceutical agents and nucleic acids. Among these, drug delivery technology has made discernible progress in recent years and the areas that warrant further focus and consideration towards technological developments have also been recognized. Development of viable methods for on-demand spatial and temporal release of entrapped drugs from the nanocarriers is an arena that is likely to enhance the clinical suitability of drug-loaded nanocarriers. One such approach, which utilizes light as the external stimulus to disrupt and/or destabilize drug-loaded nanoparticles, will be the discussion platform of this article. Although several phototriggerable nanocarriers are currently under development, I will limit this review to the phototriggerable liposomes that have demonstrated promise in the cell culture systems at least (but not the last). The topics covered in this review include (i) a brief summary of various phototriggerable nanocarriers; (ii) an overview of the application of liposomes to deliver payload of photosensitizers and associated technologies; (iii) the design considerations of photoactivable lipid molecules and the chemical considerations and mechanisms of phototriggering of liposomal lipids; (iv) limitations and future directions for in vivo, clinically viable triggered drug delivery approaches and potential novel photoactivation strategies will be discussed. PMID:24662363

  19. Mannosylated liposomes for bio-film targeting.

    PubMed

    Vyas, S P; Sihorkar, Vaibhav; Jain, Sanyog

    2007-02-07

    Vesicular systems in general are investigated to achieve bacterial bio-film targeting as their architecture mimics bio-membranes in terms of structure and bio-behavior. This paper elaborates upon the role of the inherent characteristics of the carrier system and further envisages the role of anchored ligands in navigating the contents in the vicinity of bio-films. Vesicles in the present study were coated with hydrophobic derivatives of mannan (cholesteryl mannan and sialo-mannan). The prepared vesicles were characterized for size, shape, percentage entrapment and ligand binding specificity and results were compared with the uncoated versions. Using a set of in vitro and in vivo models, the bio-film targeting potential of plain and mannosylated liposomal formulations were compared. Results suggested that mannosylated vesicles could be effectively targeted to the model bacterial bio-films, compared with plain vesicles. Moreover, the sialo-mannan coated liposomes recorded superior targetability as reflected in the significantly higher percentage growth inhibition when compared with cholesteryl mannan coated liposomes. The engineered systems thus have the potential use for the delivery of anti-microbial agents to the bio-films.

  20. Targeting of liposome-associated calcipotriol to the skin: effect of liposomal membrane fluidity and skin barrier integrity.

    PubMed

    Knudsen, Nina Østergaard; Jorgensen, Lene; Hansen, Jens; Vermehren, Charlotte; Frokjaer, Sven; Foged, Camilla

    2011-09-20

    Many dermal diseases like psoriasis are characterized by major changes in skin barrier function, which challenge the reproducible delivery of drugs into specific layers of diseased skin. The purpose of this study was to elucidate how liposomal bilayer fluidity and barrier integrity affected the delivery of liposome-associated calcipotriol to the skin. Calcipotriol-containing gel state and liquid state dipalmitoylphosphatidyl-choline:dilauroylphosphatidylcholine liposomes were prepared by extrusion. Using Langmuir monolayers, calcipotriol was shown to affect the packing of the lipid membrane. The penetration of radioactively labeled lipid and calcipotriol into pig skin was examined using the Franz diffusion cell model, and tape stripping was applied to impose an impaired barrier. Distorting the skin barrier resulted in an enhanced penetration of lipid from both gel and liquid state liposomes. In addition, increased penetration of lipid from liquid state liposomes was observed compared to gel state liposomes into barrier-impaired skin. For barrier-impaired skin, an elevated calcipotriol-to-lipid ratio was found in the receptor fluid for both liposome compositions indicating that calcipotriol is released from the vesicles. This suggests that the liposome-mediated delivery of calcipotriol to the epidermis of diseased skin is affected by the fluidity of the liposomal membrane. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Peritoneal retention of liposomes: Effects of lipid composition, PEG coating and liposome charge.

    PubMed

    Dadashzadeh, S; Mirahmadi, N; Babaei, M H; Vali, A M

    2010-12-01

    In the treatment of peritoneal carcinomatosis, systemic chemotherapy is not quite effective due to the poor penetration of cytotoxic agents into the peritoneal cavity, whereas intraperitoneal administration of chemotherapeutic agents is generally accompanied by quick absorption of the free drug from the peritoneum. Local delivery of drugs with controlled-release delivery systems like liposomes could provide sustained, elevated drug levels and reduce local and systemic toxicity. In order to achieve an ameliorated liposomal formulation that results in higher peritoneal levels of the drug and retention, vesicles composed of different phospholipid compositions (distearoyl [DSPC]; dipalmitoyl [DPPC]; or dimiristoylphosphatidylcholine [DMPC]) and various charges (neutral; negative, containing distearoylphosphatidylglycerol [DSPG]; or positive, containing dioleyloxy trimethylammonium propane [DOTAP]) were prepared at two sizes of 100 and 1000nm. The effect of surface hydrophilicity was also investigated by incorporating PEG into the DSPC-containing neutral and charged liposomes. Liposomes were labeled with (99m)Tc and injected into mouse peritoneum. Mice were then sacrificed at eight different time points, and the percentage of injected radiolabel in the peritoneal cavity and the tissue distribution in terms of the percent of the injected dose/gram of tissue (%ID/g) were obtained. The ratio of the peritoneal AUC to the free label ranged from a minimum of 4.95 for DMPC/CHOL (cholesterol) 100nm vesicles to a maximum of 24.99 for DSPC/CHOL/DOTAP 1000nm (DOTAP 1000) vesicles. These last positively charged vesicles had the greatest peritoneal level; moreover, their level remained constant at approximately 25% of the injected dose from 2 to 48h. Among the conventional (i.e., without PEG) 100nm liposomes, the positively charged vesicles again showed the greatest retention. Incorporation of PEG at this size into the lipid structures augmented the peritoneal level, particularly

  2. Liposomal nanoparticles as a drug delivery vehicle against osteosarcoma

    NASA Astrophysics Data System (ADS)

    Dhule, Santosh Subhashrao

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

  3. Binding of Diphtheria Toxin to Phospholipids in Liposomes

    NASA Astrophysics Data System (ADS)

    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

  4. Cationic liposomes evoke proinflammatory mediator release and neutrophil extracellular traps (NETs) toward human neutrophils.

    PubMed

    Hwang, Tsong-Long; Hsu, Ching-Yun; Aljuffali, Ibrahim A; Chen, Chun-Han; Chang, Yuan-Ting; Fang, Jia-You

    2015-04-01

    Cationic liposomes are widely used as nanocarriers for therapeutic and diagnostic purposes. The cationic components of liposomes can induce inflammatory responses. This study examined the effect of cationic liposomes on human neutrophil activation. Cetyltrimethylammonium bromide (CTAB) or soyaethyl morpholinium ethosulfate (SME) was incorporated into liposomes as the cationic additive. The liposomes' cytotoxicity and their induction of proinflammatory mediators, intracellular calcium, and neutrophil extracellular traps (NETs) were investigated. The interaction of the liposomes with the plasma membrane triggered the stimulation of neutrophils. CTAB liposomes induced complete leakage of lactate dehydrogenase (LDH) at all concentrations tested, whereas SME liposomes released LDH in a concentration-dependent manner. CTAB liposomes proved to more effectively activate neutrophils compared with SME liposomes, as indicated by increased superoxide anion and elastase levels. Calcium influx increased 9-fold after treatment with CTAB liposomes. This influx was not changed by SME liposomes compared with the untreated control. Scanning electron microscopy (SEM) and immunofluorescence images indicated the presence of NETs after treatment with cationic liposomes. NETs could be quickly formed, within minutes, after CTAB liposomal treatment. In contrast to this result, NET formation was slowly and gradually increased by SME liposomes, within 4h. Based on the data presented here, it is important to consider the toxicity of cationic liposomes during administration in the body. This is the first report providing evidence of NET production induced by cationic liposomes. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Liposomal encapsulation of a near-infrared fluorophore enhances fluorescence quenching and reliable whole body optical imaging upon activation in vivo.

    PubMed

    Tansi, Felista L; Rüger, Ronny; Rabenhold, Markus; Steiniger, Frank; Fahr, Alfred; Kaiser, Werner A; Hilger, Ingrid

    2013-11-11

    In the past decade, there has been significant progress in the development of water soluble near-infrared fluorochromes for use in a wide range of imaging applications. Fluorochromes with high photo and thermal stability, sensitivity, adequate pharmacological properties and absorption/emission maxima within the near infrared window (650-900 nm) are highly desired for in vivo imaging, since biological tissues show very low absorption and auto-fluorescence at this spectrum window. Taking these properties into consideration, a myriad of promising near infrared fluorescent probes has been developed recently. However, a hallmark of most of these probes is a rapid clearance in vivo, which hampers their application. It is hypothesized that encapsulation of the near infrared fluorescent dye DY-676-COOH, which undergoes fluorescence quenching at high concentrations, in the aqueous interior of liposomes will result in protection and fluorescence quenching, which upon degradation by phagocytes in vivo will lead to fluorescence activation and enable imaging of inflammation. Liposomes prepared with high concentrations of DY-676-COOH reveal strong fluorescence quenching. It is demonstrated that the non-targeted PEGylated fluorescence-activatable liposomes are taken up predominantly by phagocytosis and degraded in lysosomes. Furthermore, in zymosan-induced edema models in mice, the liposomes are taken up by monocytes and macrophages which migrate to the sites of inflammation. Opposed to free DY-676-COOH, prolonged stability and retention of liposomal-DY-676-COOH is reflected in a significant increase in fluorescence intensity of edema. Thus, protected delivery and fluorescence quenching make the DY-676-COOH-loaded liposomes a highly promising contrast agent for in vivo optical imaging of inflammatory diseases.

  6. Comparison of in vivo Adjuvanticity of Liposomal PO CpG ODN with Liposomal PS CpG ODN: Soluble Leishmania Antigens as a Model

    PubMed Central

    Golali, Ensieh; Jaafari, Mahmoud Reza; Khamesipour, Ali; Abbasi, Azam; Saberi, Zahra; Badiee, Ali

    2012-01-01

    Objective(s) CpG oligodeoxynucleotides (CpG ODNs) have been shown to have potent immunostimulatory adjuvant activity for a wide range of antigens. Due to susceptibility of phosphodiester CpG ODNs (PO CpG) to nuclease degradation, nuclease-resistant phosphorothioate CpG ODNs (PS CpG) were currently utilized in an in vivo model. In this study, according to some recently reported drawbacks with PS CpG, the adjuvant potential of liposomal PO CpG as a substitute for PS CpG was evaluated. Materials and Methods Soluble Leishmania antigens (SLA) as a model antigen and distearoylphosphatidylcoline (DSPC) as a neutral lipid were employed to prepare liposomes. Susceptible BALB/c mice received buffer, SLA, Lip-SLA, Lip-SLA-PS CpG, Lip-SLA-PO CpG, SLA+PS CpG, or SLA+PO CpG subcutaneously 3 times with 3 weeks intervals and then were challenged with Leishmania major’s live promastigotes. Blood and spleen samples were analyzed to determine the level and type of antibodies and cytokines. The number of live parasites in the spleen of immunized mice was determined. Moreover, the lesion size progress was assessed weekly by footpad swelling measurement. Results The results showed that mice immunized with Lip-SLA-PS CpG or Lip-SLA-PO CpG developed a significantly smaller footpad swelling, higher level of anti SLA IgG antibodies before and after challenge, and lower spleen parasite burden compared with the control groups. However, there was no significant difference between mice received Lip-SLA-PS CpG and those received Lip-SLA-PO CpG. Conclusion The results demonstrated that liposomal PO CpG ODN could be used instead of PS CpG ODN to overcome the possible drawbacks. PMID:23493437

  7. Sphingomyelin Liposomes Containing Porphyrin-phospholipid for Irinotecan Chemophototherapy

    PubMed Central

    Carter, Kevin A; Luo, Dandan; Razi, Aida; Geng, Jumin; Shao, Shuai; Ortega, Joaquin; Lovell, Jonathan F

    2016-01-01

    Porphyrin-phospholipid (PoP) liposomes can entrap anti-cancer agents and release them in response to near infrared (NIR) light. Doxorubicin, when remotely loaded via an ammonium sulfate gradient at a high drug-to-lipid ratio, formed elongated crystals that altered liposome morphology and could not be loaded into liposomes with higher PoP content. On the other hand, irinotecan could also be remotely loaded but did not form large crystals and did not induce liposome elongation. The loading, stability, and NIR light-triggered release of irinotecan in PoP liposomes was altered by the types of lipids used and the presence of PEGylation. Sphingomyelin, which has been explored previously for liposomal irinotecan, was found to produce liposomes with relatively improved serum stability and rapid NIR light-triggered drug release. PoP liposomes composed from sphingomyelin, cholesterol and 2 molar percent PoP rapidly released irinotecan in vivo in response to NIR irradiation as monitored by intravital microscopy and also induced effective tumor eradication in mice bearing MIA Paca-2 subcutaneous tumor xenografts. PMID:27877238

  8. Biodistribution of liposome-entrapped human gamma-globulin.

    PubMed

    García-Santana, María A; Duconge, Jorge; Sarmiento, María E; Lanio-Ruíz, María E; Becquer, María A; Izquierdo, Luís; Acosta-Domínguez, Armando

    2006-09-01

    The present study was aimed at the preparation and performance evaluation of Intacglobin-loaded liposomes for selective drug presentation to the lungs. Egg phosphatidylcholine- and cholesterol-based liposomes (1:1 and 1:0.25 mol/mol) were prepared by a dehydration-rehydration procedure. A tissue distribution study after single intranasal administration of 0.5 microCi 125I-Intacglobin-loaded liposomes was conducted in Balb/c mice. The efficiencies of drug entrapment (30%) and the average diameters did not differ significantly between the two liposome formulations. However, liposomes composed of an increased cholesterol amount showed a lower in vitro drug release rate. The airway penetration efficiency of the liposomal formulation was determined by the cumulative percentage of the dose reaching the lungs (AUC) and its sojourn time therein, and were 1.7- and 2.2-times higher compared with the plain 125I- Intacglobin solution-based formulation, respectively. A significantly greater (p<0.001) drug localization index after 24 h was found at the lungs in comparison with the other tissues (p<0.01), although similar values were detected between groups following administration of either liposomes or control solutions, despite the formulations attributes. In conclusion, it is suggested that longer Intacglobin exposure at the pulmonary region is observed after administration of the liposomal formulation. The results open future perspectives in assessing local passive immunization for the treatment of respiratory infectious diseases.

  9. Enzyme-Responsive Liposomes for the Delivery of Anticancer Drugs.

    PubMed

    Fouladi, Farnaz; Steffen, Kristine J; Mallik, Sanku

    2017-03-08

    Liposomes are nanocarriers that deliver the payloads at the target site, leading to therapeutic drug concentrations at the diseased site and reduced toxic effects in healthy tissues. Several approaches have been used to enhance the ability of the nanocarrier to target the specific tissues, including ligand-targeted liposomes and stimuli-responsive liposomes. Ligand-targeted liposomes exhibit higher uptake by the target tissue due to the targeting ligand attached to the surface, while the stimuli-responsive liposomes do not release their cargo unless they expose to an endogenous or exogenous stimulant at the target site. In this review, we mainly focus on the liposomes that are responsive to pathologically increased levels of enzymes at the target site. Enzyme-responsive liposomes release their cargo upon contact with the enzyme through several destabilization mechanisms: (1) structural perturbation in the lipid bilayer, (2) removal of a shielding polymer from the surface and increased cellular uptake, (3) cleavage of a lipopeptide or lipopolymer incorporated in the bilayer, and (4) activation of a prodrug in the liposomes.

  10. Sustainable proliferation of liposomes compatible with inner RNA replication

    PubMed Central

    Tsuji, Gakushi; Fujii, Satoshi; Sunami, Takeshi; Yomo, Tetsuya

    2016-01-01

    Although challenging, the construction of a life-like compartment via a bottom–up approach can increase our understanding of life and protocells. The sustainable replication of genome information and the proliferation of phospholipid vesicles are requisites for reconstituting cell growth. However, although the replication of DNA or RNA has been developed in phospholipid vesicles, the sustainable proliferation of phospholipid vesicles has remained difficult to achieve. Here, we demonstrate the sustainable proliferation of liposomes that replicate RNA within them. Nutrients for RNA replication and membranes for liposome proliferation were combined by using a modified freeze–thaw technique. These liposomes showed fusion and fission compatible with RNA replication and distribution to daughter liposomes. The RNAs in daughter liposomes were repeatedly used as templates in the next RNA replication and were distributed to granddaughter liposomes. Liposome proliferation was achieved by 10 cycles of iterative culture operation. Therefore, we propose the use of culturable liposomes as an advanced protocell model with the implication that the concurrent supplement of both the membrane material and the nutrients of inner reactions might have enabled protocells to grow sustainably. PMID:26711996

  11. Improved Tumor Uptake by Optimizing Liposome Based RES Blockade Strategy

    PubMed Central

    Sun, Xiaolian; Yan, Xuefeng; Jacobson, Orit; Sun, Wenjing; Wang, Zhantong; Tong, Xiao; Xia, Yuqiong; Ling, Daishun; Chen, Xiaoyuan

    2017-01-01

    Minimizing the sequestration of nanomaterials (NMs) by the reticuloendothelial system (RES) can enhance the circulation time of NMs, and thus increase their tumor-specific accumulation. Liposomes are generally regarded as safe (GRAS) agents that can block the RES reversibly and temporarily. With the help of positron emission tomography (PET), we monitored the in vivo tissue distribution of 64Cu-labeled 40 × 10 nm gold nanorods (Au NRs) after pretreatment with liposomes. We systematically studied the effectiveness of liposome administration by comparing (1) differently charged liposomes; (2) different liposome doses; and (3) varying time intervals between liposome dose and NR dose. By pre-injecting 400 μmol/kg positively charged liposomes into mice 5 h before the Au NRs, the liver and spleen uptakes of Au NRs decreased by 30% and 53%, respectively. Significantly, U87MG tumor uptake of Au NRs increased from 11.5 ± 1.1 %ID/g to 16.1 ± 1.3 %ID/g at 27 h post-injection. Quantitative PET imaging is a valuable tool to understand the fate of NMs in vivo and cationic liposomal pretreatment is a viable approach to reduce RES clearance, prolong circulation, and improve tumor uptake. PMID:28042337

  12. Sustainable proliferation of liposomes compatible with inner RNA replication.

    PubMed

    Tsuji, Gakushi; Fujii, Satoshi; Sunami, Takeshi; Yomo, Tetsuya

    2016-01-19

    Although challenging, the construction of a life-like compartment via a bottom-up approach can increase our understanding of life and protocells. The sustainable replication of genome information and the proliferation of phospholipid vesicles are requisites for reconstituting cell growth. However, although the replication of DNA or RNA has been developed in phospholipid vesicles, the sustainable proliferation of phospholipid vesicles has remained difficult to achieve. Here, we demonstrate the sustainable proliferation of liposomes that replicate RNA within them. Nutrients for RNA replication and membranes for liposome proliferation were combined by using a modified freeze-thaw technique. These liposomes showed fusion and fission compatible with RNA replication and distribution to daughter liposomes. The RNAs in daughter liposomes were repeatedly used as templates in the next RNA replication and were distributed to granddaughter liposomes. Liposome proliferation was achieved by 10 cycles of iterative culture operation. Therefore, we propose the use of culturable liposomes as an advanced protocell model with the implication that the concurrent supplement of both the membrane material and the nutrients of inner reactions might have enabled protocells to grow sustainably.

  13. Liposomal gel with chloramphenicol: characterisation and in vitro release.

    PubMed

    Pavelić, Zeljka; Skalko-Basnet, Natasa; Jalsenjak, Ivan

    2004-12-01

    The aim of our study was to develop a liposomal carrier system for the local treatment of bacterial vaginosis, capable to efficiently deliver entrapped drug during an extended period of time. Chloramphenicol was entrapped in liposomes composed of egg phosphatidylcholine/egg phosphatidylgycerol-sodium (9:1, molar ratio) and prepared by two different methods, the proliposome method and the polyol dilution method. Both liposome preparations were characterised and compared for particle size, polydispersity, entrapment efficiency and tested for in vitro stability in media that simulate human vaginal conditions (buffer pH 4.5 and vaginal fluid simulant). To achieve application viscosity of liposomes and to further improve their stability, liposomes prepared by the proliposome method were incorporated in the bioadhesive gel made of Carbopol 974P NF resin. In vitro release studies of liposomes incorporated in the gel have shown a prolonged release of entrapped chloramphenicol compared to control gel. Even after 24 hours of incubation in the vaginal fluid simulant, more than 40% of the originally entrapped drug was still retained in the gel. Storage stability studies have proven the ability of the Carbopol 974P NF gel to preserve the original size distribution of incorporated liposomes. All the performed experiments confirm the applicability of liposomes as a novel drug carrier system for the local treatment of bacterial vaginosis.

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

    PubMed Central

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

    2016-01-01

    Hybrid liposome/metal nanoparticles are promising candidate materials for biomedical applications. However, the poor selectivity and low yield of the desired hybrid during synthesis pose a challenge. We designed a programmable liposome by selective encoding of a reducing agent, which allows self-crystallization of metal nanoparticles within the liposome to produce stable liposome/metal nanoparticles alone. We synthesized seven types of liposome/monometallic and more complex liposome/bimetallic hybrids. The resulting nanoparticles are tunable in size and metal composition, and their surface plasmon resonance bands are controllable in visible and near infrared. Owing to outer lipid bilayer, our liposome/Au nanoparticle shows better colloidal stability in biologically relevant solutions as well as higher endocytosis efficiency than gold nanoparticles without the liposome. We used this hybrid in intracellular imaging of living cells via surface-enhanced Raman spectroscopy, taking advantage of its improved physicochemical properties. We believe that our method greatly increases the utility of metal nanoparticles in in vivo applications. PMID:28028544

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

    PubMed

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

    2013-02-01

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

  16. Enzymatic reactions in liposomes using the detergent-induced liposome loading method.

    PubMed

    Oberholzer, T; Meyer, E; Amato, I; Lustig, A; Monnard, P A

    1999-01-12

    Microcompartmentalization is a crucial step in the origin of life. More than 30 years ago, Oparin et al. proposed models based on biochemical reactions taking place in so-called coacervates. Their intention was to develop systems with which semipermeable microcompartments could be established. In the present work we follow their intuition, but we use well-characterized bilayer structures instead of the poorly characterized coacervates. Liposomes from phospholipids can be used as microreactors but they exhibit only a modest permeability and, therefore, chemical reactions occurring inside these structures are depleted after a relatively short period. Here it is shown that even highly stable liposomes from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) can be used as semipermeable microreactors when treated with sodium cholate. Using this kind of mixed liposomes, we describe a biochemical reaction occurring inside the liposomes while the same reaction is prevented in the external medium. In addition, we show that this cholate-induced permeability of POPC bilayers can even be used to load macromolecules such as enzymes from the outside.

  17. Electromagnetic field triggered drug and chemical delivery via liposomes

    DOEpatents

    Liburdy, Robert P.

    1993-01-01

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

  18. Recent Developments of Liposomes as Nanocarriers for Theranostic Applications

    PubMed Central

    Xing, Hang; Hwang, Kevin; Lu, Yi

    2016-01-01

    Liposomes are nanocarriers comprised of lipid bilayers encapsulating an aqueous core. The ability of liposomes to encapsulate a wide variety of diagnostic and therapeutic agents has led to significant interest in utilizing liposomes as nanocarriers for theranostic applications. In this review, we highlight recent progress in developing liposomes as nanocarriers for a) diagnostic applications to detect proteins, DNA, and small molecule targets using fluorescence, magnetic resonance, ultrasound, and nuclear imaging; b) therapeutic applications based on small molecule-based therapy, gene therapy and immunotherapy; and c) theranostic applications for simultaneous detection and treatment of heavy metal toxicity and cancers. In addition, we summarize recent studies towards understanding of interactions between liposomes and biological components. Finally, perspectives on future directions in advancing the field for clinical translations are also discussed. PMID:27375783

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

    PubMed Central

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

    2015-01-01

    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. PMID:26610702

  20. Use of Adaptive Focused Acoustics™ ultrasound in controlling liposome formation.

    PubMed

    Shen, Katherine C; Kakumanu, Srikanth; Beckett, Carl D; Laugharn, James A

    2015-11-01

    Many techniques for producing large unilamellar vesicles (LUVs) or small unilamellar vesicles (SUVs) have drawbacks, including exposure of sensitive biological materials to harsh organic solvents or high temperatures. Here we describe the use of controlled focused ultrasound, Adaptive Focused Acoustics™ (AFA), to make LUV or SUV at low temperature without organic solvents and at a consistent, chosen size. We studied the effects of peak incident power (PIP), cycles per burst (CPB), duty factor (DF), temperature, and lipid composition (natural or synthetic), on liposome size distribution. We found that an increase in PIP, DF, CPB, or temperature decreased liposome size. When processed under the same conditions as the natural lipid composition [Phospholipon 90 G], the synthetic lipid composition [HSPC, DSPE-PEG-2000, Chol] generally produced larger liposomes, although extending processing time reduced liposomes to similar size. In combination with AFA, these trends can help pinpoint parameter values that achieve a desired liposome size distribution.

  1. Shrinkage of pegylated and non-pegylated liposomes in serum.

    PubMed

    Wolfram, Joy; Suri, Krishna; Yang, Yong; Shen, Jianliang; Celia, Christian; Fresta, Massimo; Zhao, Yuliang; Shen, Haifa; Ferrari, Mauro

    2014-02-01

    An essential requisite for the design of nanodelivery systems is the ability to characterize the size, homogeneity and zeta potential of nanoparticles. Such properties can be tailored in order to create the most efficient drug delivery platforms. An important question is whether these characteristics change upon systemic injection. Here, we have studied the behavior of phosphatidylcholine/cholesterol liposomes exposed to serum proteins. The results reveal a serum-induced reduction in the size and homogeneity of both pegylated and non-pegylated liposomes, implicating the possible role of osmotic forces. In addition, changes to zeta-potential were observed upon exposing liposomes to serum. The liposomes with polyethylene glycol expressed different characteristics than their non-polymeric counterparts, suggesting the potential formation of a denser protein corona around the non-pegylated liposomes.

  2. Microfabrication of three-dimensional filters for liposome extrusion

    NASA Astrophysics Data System (ADS)

    Baldacchini, Tommaso; Nuñez, Vicente; LaFratta, Christopher N.; Grech, Joseph S.; Vullev, Valentine I.; Zadoyan, Ruben

    2015-03-01

    Liposomes play a relevant role in the biomedical field of drug delivery. The ability of these lipid vesicles to encapsulate and transport a variety of bioactive molecules has fostered their use in several therapeutic applications, from cancer treatments to the administration of drugs with antiviral activities. Size and uniformity are key parameters to take into consideration when preparing liposomes; these factors greatly influence their effectiveness in both in vitro and in vivo experiments. A popular technique employed to achieve the optimal liposome dimension (around 100 nm in diameter) and uniform size distribution is repetitive extrusion through a polycarbonate filter. We investigated two femtosecond laser direct writing techniques for the fabrication of three-dimensional filters within a microfluidics chip for liposomes extrusion. The miniaturization of the extrusion process in a microfluidic system is the first step toward a complete solution for lab-on-a-chip preparation of liposomes from vesicles self-assembly to optical characterization.

  3. The hypoglycaemic response of diabetic rats to insulin-liposomes.

    PubMed

    Petkowicz, J; Byra, A; Szumiło, T

    1990-01-01

    We prepared insulin-liposomes using one combination of lipids including phosphatidylcholine (cholesterol) stearylamine, 7/2/1 (molar ratio). Non-sonicated liposomes (LMV) and sonicated liposomes (SUV) contained about 20% and 5% of insulin, respectively. Free insulin was removed from liposomes-associated insulin by ultracentrifugation, or ultrafiltration on Sepharose 6B column. Insulin preparations were administered parenterally and non-parenterally into male, Wistar rats with alloxan diabetes to produce the hypoglycaemia. In case of i.v. and s.c. routes of administration all preparations acted in the similar manner giving the clear hypoglycaemia after 2 h. When administered intragastrically only liposome insulin caused hypoglycaemia. In case of buccal and nasal routes of administration only SUV-insulin was effective.

  4. Ultrasound triggered drug delivery with liposomal nested microbubbles.

    PubMed

    Wallace, N; Wrenn, S P

    2015-12-01

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

  5. Electromagnetic field triggered drug and chemical delivery via liposomes

    DOEpatents

    Liburdy, R.P.

    1993-03-02

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

  6. Liposomal resiquimod for the treatment of Leishmania donovani infection

    PubMed Central

    Peine, Kevin J.; Gupta, Gaurav; Brackman, Deanna J.; Papenfuss, Tracey L.; Ainslie, Kristy M.; Satoskar, Abhay R.; Bachelder, Eric M.

    2014-01-01

    Objectives The imidazoquinoline family of drugs are Toll-like receptor 7/8 agonists that have previously been used in the treatment of cutaneous leishmaniasis. Because of the hydrophobic nature of imidazoquinolines, they are traditionally not administered systemically for the treatment of visceral leishmaniasis. We formulated liposomal resiquimod, an imidazoquinoline, for the systemic treatment of visceral leishmaniasis. Methods By using lipid film hydration with extrusion, we encapsulated resiquimod in liposomes. These liposomes were then injected intravenously to treat BALB/c mice infected with Leishmania donovani. Results Treatment with liposomal resiquimod significantly decreased the parasite load in the liver, spleen and bone marrow. In addition, resiquimod treatment increased interferon-γ and interleukin-10 production in an antigen recall assay. Resiquimod was shown to be non-toxic in histology and in vitro culture experiments. Conclusions FDA-approved resiquimod, in a liposomal formulation, displays promising results in treating visceral leishmaniasis. PMID:23956375

  7. Designing liposomal adjuvants for the next generation of vaccines.

    PubMed

    Perrie, Yvonne; Crofts, Fraser; Devitt, Andrew; Griffiths, Helen R; Kastner, Elisabeth; Nadella, Vinod

    2016-04-01

    Liposomes not only offer the ability to enhance drug delivery, but can effectively act as vaccine delivery systems and adjuvants. Their flexibility in size, charge, bilayer rigidity and composition allow for targeted antigen delivery via a range of administration routes. In the development of liposomal adjuvants, the type of immune response promoted has been linked to their physico-chemical characteristics, with the size and charge of the liposomal particles impacting on liposome biodistribution, exposure in the lymph nodes and recruitment of the innate immune system. The addition of immunostimulatory agents can further potentiate their immunogenic properties. Here, we outline the attributes that should be considered in the design and manufacture of liposomal adjuvants for the delivery of sub-unit and nucleic acid based vaccines.

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

    NASA Astrophysics Data System (ADS)

    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.

  9. Enhanced antitumor effect of novel dual-targeted paclitaxel liposomes

    NASA Astrophysics Data System (ADS)

    Meng, Shuyan; Su, Bo; Li, Wei; Ding, Yongmei; Tang, Liang; Zhou, Wei; Song, Yin; Li, Heyan; Zhou, Caicun

    2010-10-01

    A novel dual-targeted peptide containing an alpha V integrins specific ligand and a neuropilin-1 specific motif was developed which showed an increased specific targeting affinity to tumors. Active dual-targeted liposomes were then produced with this peptide and exhibited greater binding activity than single-targeted liposomes in vitro. Paclitaxel entrapped in this formulation greatly increased the uptake of paclitaxel in the targeting cells and significantly suppressed the growth of HUVEC and A549 cells compared with general paclitaxel injections (Taxol) and single-targeted paclitaxel liposomes. The treatment of tumor xenograft models with dual-targeted paclitaxel liposomes also resulted in better tumor growth inhibition than any other treatment groups. Therefore, the dual-targeted paclitaxel liposomes prepared in the present study might be a more promising drug for cancer treatment. Furthermore, the dual-targeting approach may produce synergistic effects that can be applied in the development of new targeted drug delivery systems.

  10. Recent Developments in Liposome-Based Veterinary Therapeutics

    PubMed Central

    2013-01-01

    Recent advances in nanomedicine have been studied in the veterinary field and have found a wide variety of applications. The past decade has witnessed a massive surge of research interest in liposomes for delivery of therapeutic substances in animals. Liposomes are nanosized phospholipid vesicles that can serve as delivery platforms for a wide range of substances. Liposomes are easily formulated, highly modifiable, and easily administered delivery platforms. They are biodegradable and nontoxic and have long in vivo circulation time. This review focuses on recent and ongoing research that may have relevance for veterinary medicine. By examining the recent developments in liposome-based therapeutics in animal cancers, vaccines, and analgesia, this review depicts the current significance and future directions of liposome-based delivery in veterinary medicine. PMID:24222862

  11. Liposomes containing drugs for treatment of vaginal infections.

    PubMed

    Pavelić, Z; Skalko-Basnet, N; Jalsenjak, I

    1999-08-01

    To develop a novel vaginal delivery system, able to effectively deliver entrapped drugs during an extended period of time at the site of action, liposomes made of phosphatidylcholine were prepared by two different methods, namely the polyol dilution method and the proliposome method. Liposomes containing three commonly applied drugs in the treatment of vaginal infections: clotrimazole, metronidazole and chloramphenicol were tested for in vitro stability (in buffers at pH 4.5 and 5.9 representing pre- and postmenopausal vaginal pH). In situ stability (in the presence of cow vaginal mucosa) showed that after 6 h incubation (at 37 degrees C), liposomes retained more than 40% of originally entrapped clotrimazole, 28% of entrapped metronidazole or 37% of entrapped chloramphenicol. In vitro and in situ stability studies confirmed the applicability of liposomes as a carrier system for vaginal delivery. Even after 24 h of incubation in the presence of vaginal mucosa liposomes retained sufficient amounts of entrapped drugs.

  12. Current Trends in Development of Liposomes for Targeting Bacterial Biofilms

    PubMed Central

    Rukavina, Zora; Vanić, Željka

    2016-01-01

    Biofilm targeting represents a great challenge for effective antimicrobial therapy. Increased biofilm resistance, even with the elevated concentrations of very potent antimicrobial agents, often leads to failed therapeutic outcome. Application of biocompatible nanomicrobials, particularly liposomally-associated nanomicrobials, presents a promising approach for improved drug delivery to bacterial cells and biofilms. Versatile manipulations of liposomal physicochemical properties, such as the bilayer composition, membrane fluidity, size, surface charge and coating, enable development of liposomes with desired pharmacokinetic and pharmacodynamic profiles. This review attempts to provide an unbiased overview of investigations of liposomes destined to treat bacterial biofilms. Different strategies including the recent advancements in liposomal design aiming at eradication of existing biofilms and prevention of biofilm formation, as well as respective limitations, are discussed in more details. PMID:27231933

  13. Cell penetrating peptide conjugated liposomes as transdermal delivery system of Polygonum aviculare L. extract.

    PubMed

    Kwon, Soon Sik; Kim, Sun Young; Kong, Bong Ju; Kim, Kyeong Jin; Noh, Geun Young; Im, Na Ri; Lim, Ji Won; Ha, Ji Hoon; Kim, Junoh; Park, Soo Nam

    2015-04-10

    In this study, Polygonum aviculare L. extract, which has superior antioxidative and cellular membrane protective activity, was loaded onto cell penetrating peptide (CPP) conjugated liposomes to enhance transdermal delivery. The physical characteristics of typical liposomes and CPP-conjugated liposomes containing P. aviculare extract were evaluated. The particle sizes of both liposomes were approximately 150 nm. Whereas the zeta potential of typical liposomes was -45 mV, that of CPP-conjugated liposomes was +42 mV. The loading efficiency of P. aviculare extract in both liposomes was calculated to be about 83%. Fluorescent-labeled liposomes were prepared to evaluate cellular uptake and skin permeation efficiency. Using flow cytometry, we found that CPP-conjugated liposomes improved cellular uptake of the fluorescent dye as compared with the typical liposomes. In addition, the skin permeation of CPP-conjugated liposomes was proved higher than that of typical liposomes by confocal laser scanning microscopy studies and Franz diffusion cell experiments. The improved cellular uptake and skin permeation of the CPP-conjugated liposomes were due to the cationic arginine-rich peptide. In vivo studies also determined that the CPP-conjugated liposomes were more effective in depigmentation and anti-wrinkle studies than typical liposomes. These results indicate that the CPP-conjugated liposomes could be effective for transdermal drug delivery of antioxidant and anti-aging therapeutics.

  14. Light induced cytosolic drug delivery from liposomes with gold nanoparticles.

    PubMed

    Lajunen, Tatu; Viitala, Lauri; Kontturi, Leena-Stiina; Laaksonen, Timo; Liang, Huamin; Vuorimaa-Laukkanen, Elina; Viitala, Tapani; Le Guével, Xavier; Yliperttula, Marjo; Murtomäki, Lasse; Urtti, Arto

    2015-04-10

    Externally triggered drug release at defined targets allows site- and time-controlled drug treatment regimens. We have developed liposomal drug carriers with encapsulated gold nanoparticles for triggered drug release. Light energy is converted to heat in the gold nanoparticles and released to the lipid bilayers. Localized temperature increase renders liposomal bilayers to be leaky and triggers drug release. The aim of this study was to develop a drug releasing system capable of releasing its cargo to cell cytosol upon triggering with visible and near infrared light signals. The liposomes were formulated using either heat-sensitive or heat- and pH-sensitive lipid compositions with star or rod shaped gold nanoparticles. Encapsulated fluorescent probe, calcein, was released from the liposomes after exposure to the light. In addition, the pH-sensitive formulations showed a faster drug release in acidic conditions than in neutral conditions. The liposomes were internalized into human retinal pigment epithelial cells (ARPE-19) and human umbilical vein endothelial cells (HUVECs) and did not show any cellular toxicity. The light induced cytosolic delivery of calcein from the gold nanoparticle containing liposomes was shown, whereas no cytosolic release was seen without light induction or without gold nanoparticles in the liposomes. The light activated liposome formulations showed a controlled content release to the cellular cytosol at a specific location and time. Triggering with visual and near infrared light allows good tissue penetration and safety, and the pH-sensitive liposomes may enable selective drug release in the intracellular acidic compartments (endosomes, lysosomes). Thus, light activated liposomes with gold nanoparticles are an attractive option for time- and site-specific drug delivery into the target cells.

  15. Image-Guided Predictions of Liposome Transport in Solid Tumours

    NASA Astrophysics Data System (ADS)

    Stapleton, Shawn

    Due to the ability to preferentially accumulate and deliver drug payloads to solid tumours, liposomes have emerged as an exciting therapeutic strategy for cancer therapy. Unfortunately, the initial excitement was dampened by limited clinical results, where only negligible increases in patient survival following liposome therapy have been observed. What are the reasons for the limited clinical efficacy? Is the nanoparticle formulation optimal? Is the enhanced permeability and retention effect overstated? What are the barriers limiting the delivery of drugs to cancer cells? What is the optimal dosing and treatment schedule? Addressing these questions requires developing quantitative tools to understand the behaviour of liposomes in vivo, such as pharmacokinetics, biodistribution, intra-tumoural accumulation, and drug release. Central to each of these questions is the concept of transport - the collection of biophysical processes responsible for the delivery of molecules to tissues. Understanding transport means understanding the crucial links between the spatio-temporal accumulation of liposomes, the physicochemical properties of liposomes, and properties of the tumour microenvironment. In this thesis, a biophysical mathematical transport model is developed that when used in combination with non-invasive imaging methods can predict liposome transport in solid tumours. The mathematical transport framework is validated in its ability to predict the bulk and intra-tumoural accumulation of liposomes based on biophysical transport properties of solid tumours. Furthermore, novel imaging methods are developed and used to elucidate the crucial links between transport barriers and spatial heterogeneity in liposome accumulation. Finally, methods are presented to integrate quantitative imaging and mathematical modelling such that an accurate prediction of liposome transport in solid tumours is possible. In summary, this thesis presents and validates an image-guided mathematical

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

    PubMed

    Lu, Dongmei; Hickey, Anthony J

    2005-12-21

    The purpose of this research was to develop liposomal dry powder aerosols for protein delivery. The delivery of stable protein formulations is essential for protein subunit vaccine delivery, which requires local delivery to macrophages in the lungs. Beta-glucuronidase (GUS) was used as a model protein to evaluate dry powder liposomes as inhaled delivery vehicles. Dimyristoyl phosphatylcholine:cholesterol (7:3) was selected as the liposome composition. The lyophilization of liposomes, micronization of the powders, aerosolization using a dry powder inhaler (DPI), and in vitro aerodynamic fine particle fraction upon collection in a twin-stage liquid impinger were evaluated. After lyophilization and jet-milling, the total amount of GUS and its activity, representing encapsulation efficiency and stability, were evaluated. The GUS amount and activity were measured and compared with freshly-prepared liposomes in the presence of mannitol, 43% of initial GUS amount, 29% of GUS activity after lyophilization and 36% of GUS amount, 22% of activity after micronization were obtained. Emitted doses from dry powder inhaler were 53%, 58%, 66%, and 73% for liposome powder:mannitol carrier ratios of 1:0, 1:4, 1:9, and 1:19. Fifteen percent of the liposome particles were less than 6.4 mum in aerodynamic diameter. The results demonstrate that milled liposome powders containing protein molecules can be aerosolized effectively at a fixed flow rate. Influences of different cryoprotectants on lyophilization of protein liposome formulations are reported. The feasibility of using liposomal dry powder aerosols for protein delivery has been demonstrated but further optimization is required in the context of specific therapeutic proteins.

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

    PubMed

    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.

  18. An OEGylated thiol monolayer for the tethering of liposomes and the study of liposome interactions.

    PubMed

    Briand, Elisabeth; Humblot, Vincent; Pradier, Claire-Marie; Kasemo, Bengt; Svedhem, Sofia

    2010-06-15

    The aim of the present work is to develop a protocol for the specific immobilization of liposomes, via tethers, onto functionalized gold surfaces, and in addition to give one example for such a surface architecture. All surface functionalization steps are charcerized and controlled. First, mixed thiolate self-assembled monolayers (SAMs) prepared from COOH- and OCH(3)-terminated oligo(ethylene glycol) (OEG) alkane thiols were characterized by polarization modulation reflection absorption infrared spectroscopy (PM-RAIRS) and by X-ray photoemission spectroscopy (XPS). The composition of the mixed SAMs was found to be close to that of the thiol solution. Next, grafting of biotin conjugated with an NH(2)-terminated OEG spacer (biotin-OEG-NH(2)) to the COOH groups via conventional amine coupling was optimized with respect to the COOH/OCH(3) ratio of the SAM. The grafting of biotin-OEG-NH(2) was assessed by monitoring the binding of neutravidin and albumin to the biotinylated surfaces using quartz crystal microbalance with dissipation monitoring (QCM-D), as well as by PM-RAIRS. It was shown that a COOH/OCH(3) ratio of around 0.3 was sufficient to saturate the SAMs with neutravidin. Finally, tethering of liposomes onto the neutravidin-terminated SAMs, was achieved. As an application example, of a close packed layer of tethered liposomes was exposed to the membrane-penetrating peptide melittin. As monitored by QCM-D, the liposomes fused when interacting with the peptide and ruptured into an extended, supported lipid bilayer over the whole surface. In summary, the described surface modification has potential for the development of assays requiring tethered intact liposomes, or tethered planar bilayers. Such surface architectures are especially important for the study of transmembrane proteins and peptides.

  19. Microencapsulation structures based on protein-coated liposomes obtained through electrospraying for the stabilization and improved bioaccessibility of curcumin.

    PubMed

    Gómez-Mascaraque, Laura G; Casagrande Sipoli, Caroline; de La Torre, Lucimara Gaziola; López-Rubio, Amparo

    2017-10-15

    Novel food-grade hybrid encapsulation structures based on the entrapment of phosphatidylcholine liposomes, within a WPC matrix through electrospraying, were developed and used as delivery vehicles for curcumin. The loading capacity and encapsulation efficiency of the proposed system was studied, and the suitability of the approach to stabilize curcumin and increase its bioaccessibility was assessed. Results showed that the maximum loading capacity of the liposomes was around 1.5% of curcumin, although the loading capacity of the hybrid microencapsulation structures increased with the curcumin content by incorporation of curcumin microcrystals upon electrospraying. Microencapsulation of curcumin within the proposed hybrid structures significantly increased its bioaccessibility (∼1.7-fold) compared to the free compound, and could successfully stabilize it against degradation in PBS (pH=7.4). The proposed approach thus proved to be a promising alternative to produce powder-like functional ingredients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Delivery of aerosolized drugs encapsulated in liposomes

    SciTech Connect

    Cheng, Yung-Sung; Lyons, C.R.; Schmid, M.H.

    1995-12-01

    Mycobacterium tuberculosis (Mtb) is an infectious disease that resides in the human lung. Due to the difficulty in completely killing off the disease in infected individuals, Mtb has developed drug-resistant forms and is on the rise in the human population. Therefore, ITRI and the University of New Mexico are collaborating to explore the treatment of Mtb by an aerosolized drug delivered directly to the lungs. In conclusion, it is feasible to obtain an appropriate size and concentration of the liposomes before and after aerosolization.

  1. Analysis of individual lipoproteins and liposomes

    SciTech Connect

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

    1997-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2007-05-01

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

  3. Cadherin-integrated liposomes with potential application in a drug delivery system.

    PubMed

    Kamiya, Koki; Tsumoto, Kanta; Yoshimura, Tetsuro; Akiyoshi, Kazunari

    2011-12-01

    N-cadherin (CDH2) proteins were reconstituted with liposomes using a baculovirus expression-liposome fusion method. CDH2 budded viruses were fused with giant liposomes containing dioleoylphophogycerol/dioleoylphosphatidylcholine (DOPG/DOPC) at pH 4.5 and the localization of CDH2 on the liposome membrane was observed by confocal laser scanning microscopy. CDH2 liposomes showed Ca(2+)-dependent association. CDH2-mediated association/dissociation in CDH2 liposomes was specific to Ca(2+) and reversible. CDH2-expressing LN-229 cells (human glioblastoma cell) adhered to CDH2 liposomes and small CDH2 liposomes (diameter approximately 150 nm), in particular, were internalized by endocytosis and partly escaped endosomes. Cadherin-containing liposomes show high potential as a new cell-specific proteoliposome. The baculovirus expression-liposome fusion method is useful as a new enabling technology for biomedical applications of functional proteoliposomes.

  4. Spectroscopic studies of alpha tocopherol interaction with a model liposome and its influence on oxidation dynamics.

    PubMed

    Krilov, Dubravka; Kosović, Marin; Serec, Kristina

    2014-08-14

    The influence of α-tocopherol on the surface conformation of liposome, as a model component of lipoproteins, and its role in oxidation process were studied. FT-IR spectra from suspensions of neat liposome, mixtures of liposome and α-tocopherol and liposome with incorporated α-tocopherol were analyzed. When α-tocopherol was incorporated into liposome, intensities of some bands were decreased or increased in comparison with the spectra of liposome and α-tocopherol mixture. These changes reflect the different localization of α-tocopherol in two types of liposome suspensions. The oxidation of liposome suspensions was initiated by addition of cupric ions. After prolonged oxidation, the differences in FT-IR spectra of oxidized samples were recorded. Differences were observed in comparison with spectra of native and oxidized liposomes were analyzed. The rate of oxidation was measured by EPR oximetry. Oxidation was generally very slow, but faster in liposome without α-tocopherol, indicating the protective role of α-tocopherol against liposome oxidation. On the other hand, liposome suspensions with EDTA in the buffer were not oxidized at all, while those with α-tocopherol and liposome mixture were only slightly oxidized. In this case the consumption of oxygen was the result of liposome oxidation supported by α-tocopherol. These results reflect the ambivalent role of α-tocopherol in liposome oxidation, similarly to findings in studies of lipoprotein oxidation.

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

    PubMed

    Vermehren, Charlotte; Hansen, Harald S; Clausen-Beck, Brian; Frøkjaer, Sven

    2003-03-18

    Incorporation of the phospholipid, N-acyl-phosphatidylethanolamine (NAPE), has shown to increase the liposomal stability towards plasma components in vitro. Besides increasing the circulation-time, NAPE has been shown to contain fusiogenic properties. Hence, fusion between NAPE-liposomes and target cells may be expected, resulting in a favorable delivery of drug to the target cell. In this study, NAPE has been tested as a potential liposomal component of phosphatidylcholine-liposomes. The liposomes were characterized by size, long-term stability and phase transition temperature (T(m)). In vivo behavior of NAPE-liposomes was determined by the blood-circulation half-life in mice. A characterization of the liposomes revealed that high content of NAPE resulted in liposomes of increased size compared to pure phosphatidylcholine-liposomes. However, the liposomes showed only a slight increase in size during storage for 5 weeks. Determination of T(m) for NAPE-liposomes showed increasing values of T(m) by increasing percentage of NAPE in the liposomal bilayer, due to the higher T(m) of NAPE compared to phosphatidylcholine. Blood-clearance studies showed an initial increase in blood-circulation of liposomes containing high amounts of NAPE. Thus, these results suggest that liposomes containing high percentage of NAPE may be a promising candidate for long-circulating liposomes, possibly in combination with other stabilizing components, e.g. cholesterol. Copyright 2002 Elsevier Science B.V.

  6. Spectroscopic studies of alpha tocopherol interaction with a model liposome and its influence on oxidation dynamics

    NASA Astrophysics Data System (ADS)

    Krilov, Dubravka; Kosović, Marin; Serec, Kristina

    2014-08-01

    The influence of α-tocopherol on the surface conformation of liposome, as a model component of lipoproteins, and its role in oxidation process were studied. FT-IR spectra from suspensions of neat liposome, mixtures of liposome and α-tocopherol and liposome with incorporated α-tocopherol were analyzed. When α-tocopherol was incorporated into liposome, intensities of some bands were decreased or increased in comparison with the spectra of liposome and α-tocopherol mixture. These changes reflect the different localization of α-tocopherol in two types of liposome suspensions. The oxidation of liposome suspensions was initiated by addition of cupric ions. After prolonged oxidation, the differences in FT-IR spectra of oxidized samples were recorded. Differences were observed in comparison with spectra of native and oxidized liposomes were analyzed. The rate of oxidation was measured by EPR oximetry. Oxidation was generally very slow, but faster in liposome without α-tocopherol, indicating the protective role of α-tocopherol against liposome oxidation. On the other hand, liposome suspensions with EDTA in the buffer were not oxidized at all, while those with α-tocopherol and liposome mixture were only slightly oxidized. In this case the consumption of oxygen was the result of liposome oxidation supported by α-tocopherol. These results reflect the ambivalent role of α-tocopherol in liposome oxidation, similarly to findings in studies of lipoprotein oxidation.

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

    PubMed

    Zalba, Sara; Garrido, María J

    2013-06-01

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

  8. Development of liposomal salbutamol sulfate dry powder inhaler formulation.

    PubMed

    Huang, Wen-Hua; Yang, Zhi-Jun; Wu, Heng; Wong, Yuen-Fan; Zhao, Zhong-Zhen; Liu, Liang

    2010-01-01

    The purpose of our study was to develop a formulation of liposomal salbutamol sulfate (SBS) dry powder inhaler (DPI) for the treatment of asthma. Liposomes of high encapsulation efficiency (more than 80%) were prepared by a vesicular phospholipid gel (VPG) technique. SBS VPG liposomes were subjected to lyophilization using different kinds of cryoprotectants in various mass ratios. Coarse lactose (63-106 microm) in different mass ratios was used as a carrier. Magnesium stearate (0.5%) was added as a lubricator. The dry liposomal powders were then crushed by ball milling and sieved through a 400-mesh sieve to control the mean particle size at about 10 microm. The effects of different kinds of cryoprotectants and the amount of lactose carrier on the fine particle fraction (FPF) of SBS were investigated. The results showed that the developed formulation of liposomal dry powder inhaler was obtained using lactose as a cryoprotectant with a mass ratio of lyophilized powder to carrier lactose at 1 : 5; 0.5% magnesium stearate was used as a lubricator. The value of FPF for SBS was 41.51+/-2.22% for this formulation. Sustained release of SBS from the VPG liposomes was found in the in vitro release study. The study results offer the promising possibility of localized pulmonary liposomal SBS delivery in the anhydrous state.

  9. Cationic liposomes in double emulsions for controlled release.

    PubMed

    Wang, Qing; Rojas, Edith C; Papadopoulos, Kyriakos D

    2012-10-01

    Liposomes containing a model active component were entrapped within the internal aqueous phase (W(1)) of W(1)/O/W(2) double emulsions, thus providing a double-encapsulation system. Our motivation for the development of this system is to prevent liposomes from interacting with unfavorable physicochemical conditions and to optimize this system for dermal vaccine delivery. The choice of cationic liposomes is based on the fact that they have high penetration ability across the skin and hair follicles, and an adjuvant effect on the activation of antigen-presenting cells. Cryo-SEM images showed that liposomes are well encapsulated within the W(1) phase, indicating that most liposomes remain intact during the homogenization step of formulation fabrication. Freezing the n-hexadecane oil (O) phase of the double-encapsulation formulations preserved their stability during the storage, and subsequent oil-thawing induced progressive release of liposomes and their contents. The release mechanism upon the freeze-thaw treatment was internal coalescence followed by external coalescence. Our results also indicated that tuning the concentration of L-α-phosphatidylcholine (PC) lipid in the cationic liposomes can control the release rate from the double-encapsulation formulations. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Dual-functional drug liposomes in treatment of resistant cancers.

    PubMed

    Mu, Li-Min; Ju, Rui-Jun; Liu, Rui; Bu, Ying-Zi; Zhang, Jing-Ying; Li, Xue-Qi; Zeng, Fan; Lu, Wan-Liang

    2017-06-01

    Efficacy of regular chemotherapy is significantly hampered by multidrug resistance (MDR) and severe systemic toxicity. The reduced toxicity has been evidenced after administration of drug liposomes, consisting of the first generation of regular drug liposomes, the second generation of long-circulation drug liposomes, and the third generation of targeting drug liposomes. However, MDR of cancers remains as an unsolved issue. The objective of this article is to review the dual-functional drug liposomes, which demonstrate the potential in overcoming MDR. Herein, dual-functional drug liposomes are referring to the drug-containing phospholipid bilayer vesicles that possess a dual-function of providing the basic efficacy of drug and the extended effect of the drug carrier. They exhibit unique roles in treatment of resistant cancer via circumventing drug efflux caused by adenosine triphosphate binding cassette (ABC) transporters, eliminating cancer stem cells, destroying mitochondria, initiating apoptosis, regulating autophagy, destroying supply channels, utilizing microenvironment, and silencing genes of the resistant cancer. As the prospect of an estimation, dual-functional drug liposomes would exhibit more strength in their extended function, hence deserving further investigation for clinical validation. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Enhanced in vivo bioluminescence imaging using liposomal luciferin delivery system

    PubMed Central

    Kheirolomoom, Azadeh; Kruse, Dustin E.; Qin, Shengping; Watson, Katherine E.; Lai, Chun-Yen; Young, Lawrence J.T.; Cardiff, Robert D.; Ferrara, Katherine W.

    2009-01-01

    To provide a continuous and prolonged delivery of the substrate D-luciferin for bioluminescence imaging in vivo, luciferin was encapsulated into liposomes using either the pH-gradient or acetate-gradient method. Under optimum loading conditions, 0.17 mg luciferin was loaded per mg of lipid with 90–95% encapsulation efficiency, where active loading was 6 to 18-fold higher than obtained with passive loading. Liposomal luciferin in a long-circulating formulation had good shelf stability, with 10% release over 3-month storage at 4°C. Pharmacokinetic profiles of free and liposomal luciferin were then evaluated in transgenic mice expressing luciferase. In contrast to rapid in vivo clearance of free luciferin (t1/2=3.54 min), luciferin encapsulated into long-circulating liposomes showed a prolonged release over 24 hours. The first order release rate constant of luciferin from long-circulating liposomes, as estimated from the best fit of the analytical model to the experimental data, was 0.01 h−1. Insonation of luciferin-loaded temperature sensitive liposomes directly injected into one tumor of Met1-luc tumor-bearing mice resulted in immediate emission of light. Systemic injection of luciferin-loaded long-circulating liposomes into Met1-luc tumor-bearing mice, followed by unilateral ultrasound-induced hyperthermia, produced a gradual increase in radiance over time, reaching a peak 4–7 h post-ultrasound. PMID:19748536

  12. The effect of intercalants on the host liposome.

    PubMed

    Cohen, Yael; Weitman, Hana; Afri, Michal; Yanus, Rinat; Rudnick, Safra; Talmon, Yeshayahu; Schmidt, Judith; Aped, Pinchas; Shatz, Smadar; Ehrenberg, Benjamin; Frimer, Aryeh A

    2012-12-01

    When phospholipids are vigorously dispersed in water, liposomes are formed. In the present study, we have explored the effect of intercalant concentration on various properties of unilamellar liposomes. Liposomes were sonically intercalated with vitamin E acetate (VitEAc) and hypericin (Hy) until no difference in light transmission was observed, which reflects the formation of liposomes of minimal diameter. Our studies indicate that the intercalant structure and concentration have an influence on the liposome diameter, which could be directly measured by cryogenic transmittance electronic microscopy. Thus, intercalated VitEAc substantially decreased the diameter of unilamellar dimyristoylphosphatidylcholine liposomes, whereas Hy did not. In addition, we followed peak intensities in the absorbance and fluorescence spectra of Hy as a function of intercalant concentration in the liposomal solution. Initially, the fluorescence intensity increased linearly with concentration; however, the curve then arched asymptotically, followed by a decrease in fluorescence at yet higher concentrations. Because the Hy monomer is the only species that emits fluorescence, we believe that the decrease of fluorescence intensity is the result of Hy aggregation.

  13. Modulation of the carotenoid bioaccessibility through liposomal encapsulation.

    PubMed

    Tan, Chen; Zhang, Yating; Abbas, Shabbar; Feng, Biao; Zhang, Xiaoming; Xia, Shuqin

    2014-11-01

    The low bioaccessibility of carotenoids is currently a challenge to their incorporation in pharmaceutics, nutraceuticals and functional foods. The aim of this study was to evaluate the modulating effects of liposome encapsulation on the bioaccessibility, and its relationship with carotenoid structure and incorporated concentration. The physical stability of liposomes, lipid digestibility, carotenoids release and bioaccessibility were investigated during incubation in a simulated gastrointestinal tract. Analysis on the liposome size and morphology showed that after digestion, the majority of particles maintained spherical shape with only an increase of size in liposomes loading β-carotene or lutein. However, a large proportion of heterogeneous particles were visible in the micelle phase of liposomes loading lycopene or canthaxanthin. It was also found that the release of lutein and β-carotene from liposomes was inhibited in a simulated gastric fluid, while was slow and sustained in a simulated intestinal fluid. By contrast, lycopene and canthaxanthin exhibited fast and considerable release in the gastrointestinal media. Both carotenoid bioaccessibility and micellization content decreased with the increase of incorporated concentration. Anyway, the bioaccessibility of carotenoids after encapsulated in liposomes was in the following order: lutein>β-carotene>lycopene>canthaxanthin. Bivariate correlation analysis revealed that carotenoid bioaccessibility depended strongly on the incorporating ability of carotenoids into a lipid bilayer, loading content, and nature of the system.

  14. Aptamer-based liposomes improve specific drug loading and release.

    PubMed

    Plourde, Kevin; Derbali, Rabeb Mouna; Desrosiers, Arnaud; Dubath, Céline; Vallée-Bélisle, Alexis; Leblond, Jeanne

    2017-04-10

    Aptamer technology has shown much promise in cancer therapeutics for its targeting abilities. However, its potential to improve drug loading and release from nanocarriers has not been thoroughly explored. In this study, we employed drug-binding aptamers to actively load drugs into liposomes. We designed a series of DNA aptamer sequences specific to doxorubicin, displaying multiple binding sites and various binding affinities. The binding ability of aptamers was preserved when incorporated into cationic liposomes, binding up to 15equivalents of doxorubicin per aptamer, therefore drawing the drug into liposomes. Optimization of the charge and drug/aptamer ratios resulted in ≥80% encapsulation efficiency of doxorubicin, ten times higher than classical passively-encapsulating liposomal formulations and similar to a pH-gradient active loading strategy. In addition, kinetic release profiles and cytotoxicity assay on HeLa cells demonstrated that the release and therapeutic efficacy of liposomal doxorubicin could be controlled by the aptamer's structure. Our results suggest that the aptamer exhibiting a specific intermediate affinity is the best suited to achieve high drug loading while maintaining efficient drug release and therapeutic activity. This strategy was successfully applied to tobramycin, a hydrophilic drug suffering from low encapsulation into liposomes, where its loading was improved six-fold using aptamers. Overall, we demonstrate that aptamers could act, in addition to their targeting properties, as multifunctional excipients for liposomal formulations.

  15. Droplet-Based Production of Liposomes

    NASA Technical Reports Server (NTRS)

    Ackley, Donald E.; Forster, Anita

    2009-01-01

    A process for making monodisperse liposomes having lipid bilayer membranes involves fewer, simpler process steps than do related prior methods. First, a microfluidic, cross junction droplet generator is used to produce vesicles comprising aqueous solution droplets contained in single layer lipid membranes. The vesicles are collected in a lipid-solvent mix that is at most partially soluble in water and is less dense than is water. A layer of water is dispensed on top of the solvent. By virtue of the difference in densities, the water sinks to the bottom and the solvent floats to the top. The vesicles, which have almost the same density as that of water, become exchanged into the water instead of floating to the top. As there are excess lipids in the solvent solution, in order for the vesicles to remain in the water, the addition of a second lipid layer to each vesicle is energetically favored. The resulting lipid bilayers present the hydrophilic ends of the lipid molecules to both the inner and outer membrane surfaces. If lipids of a second kind are dissolved in the solvent in sufficient excess before use, then asymmetric liposomes may be formed.

  16. Liposomes formed in sintered glass pores.

    PubMed

    Zawada, Zygmunt H; Gubernator, Jerzy; Pentak, Danuta

    2008-01-01

    The method for preparation of vesicles, by evaporation of hydrophobic solvent from double emulsion (w/o/w) formed in the properly designed device is described. These method leads to multiple increase of encapsulation efficiency of aqueous solutions of drug in liposomes in comparison with other method. The w/o/w was passed through the glass sinter with the use of negative pressure to disrupt w/o/w drops into smaller ones. At low pressure and at heigher temperature, the hydrophobic solvent from oil phase evaporated off and the lipids that were diluted in oil phase had created bilayer. When the relatively small quantity of lipids was used, the final encapsulation efficiency (ee) was about 50% and the uppermost encapsulation volume (ev) was 160 mL/g of lipids. Similar ee was noted for a 4-amino-10-methylfolic acid (MTX), Patent Blue V (PB) and bovine serum albumin (BSA). Liposomes loaded with drug at high concentration may be easily separated from suspension with the use of simple centrifugation.

  17. Mucosal Vaccine Development Based on Liposome Technology

    PubMed Central

    Norling, Karin; Bally, Marta; Höök, Fredrik

    2016-01-01

    Immune protection against infectious diseases is most effective if located at the portal of entry of the pathogen. Hence, there is an increasing demand for vaccine formulations that can induce strong protective immunity following oral, respiratory, or genital tract administration. At present, only few mucosal vaccines are found on the market, but recent technological advancements and a better understanding of the principles that govern priming of mucosal immune responses have contributed to a more optimistic view on the future of mucosal vaccines. Compared to live attenuated vaccines, subcomponent vaccines, most often protein-based, are considered safer, more stable, and less complicated to manufacture, but they require the addition of nontoxic and clinically safe adjuvants to be effective. In addition, another limiting factor is the large antigen dose that usually is required for mucosal vaccines. Therefore, the combination of mucosal adjuvants with the recent progress in nanoparticle technology provides an attractive solution to these problems. In particular, the liposome technology is ideal for combining protein antigen and adjuvant into an effective mucosal vaccine. Here, we describe and discuss recent progress in nanoparticle formulations using various types of liposomes that convey strong promise for the successful development of the next generation of mucosal vaccines. PMID:28127567

  18. Vessel-Targeted Chemophototherapy with Cationic Porphyrin-Phospholipid Liposomes.

    PubMed

    Luo, Dandan; Geng, Jumin; Li, Nasi; Carter, Kevin A; Shao, Shuai; Atilla-Gokcumen, G Ekin; Lovell, Jonathan F

    2017-07-20

    Cationic liposomes have been used for targeted drug delivery to tumor blood vessels, via mechanisms that are not fully elucidated. Doxorubicin (Dox)-loaded liposomes were prepared that incorporate a cationic lipid; 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), along with a small amount of porphyrin-phospholipid (PoP). Near infrared (NIR) light induced release of entrapped Dox via PoP-mediated DOTAP photo-oxidation. The formulation was optimized to enable extremely rapid NIR light-triggered Dox release (i.e. in 15 seconds), while retaining reasonable serum stability. In vitro, cationic PoP liposomes readily bound both to MIA PaCa-2 human pancreatic cancer cells and human vascular endothelial cells. When administered intravenously, cationic PoP liposomes were cleared from circulation within minutes, with most accumulation in the liver and spleen. Fluorescence imaging revealed that some cationic PoP liposomes also localized at the tumor blood vessels. Compared to analogous neutral liposomes, strong tumor photo-ablation was induced with a single treatment of cationic PoP liposomes and laser irradiation (5 mg/kg Dox and 100 J/cm(2) NIR light). Unexpectedly, empty cationic PoP liposomes (lacking Dox) induced equally potent anti-tumor phototherapeutic effects as the drug loaded ones. A more balanced chemo- and photo- therapeutic response was subsequently achieved when anti-tumor studies were repeated using higher drug dosing (7 mg/kg Dox) and an ultralow fluence phototreatment (20 J/cm(2) NIR light). These results demonstrate the feasibility of vessel-targeted chemophototherapy using cationic PoP liposomes and also illustrate synergistic considerations. Copyright ©2017, American Association for Cancer Research.

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

    PubMed

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

    2016-10-15

    The present paper is aimed at development of functionalized risperidone liposomes for brain targeting through nasal route for effective therapeutic management of schizophrenia. The risperidone liposomes were prepared by thin film hydration method. Various parameters such as lipid ratio and lipid to drug ratio were optimized by using Design-Expert(®) Software to obtain high entrapment with minimum vesicle size. The surface of the optimized liposomes was modified by coating stearylamine and MPEG-DSPE for enhanced penetration to the brain. The formulations were evaluated for vesicle size, zeta potential, and entrapment efficiency. The morphology was studied by Transmission Electron Microscopy (TEM). In vivo efficacy was assessed by performing pharmacokinetic study in Wistar albino rats following intranasal administration of the formulations in comparison to intravenous bolus administration of pure drug. The mean vesicle size of optimized liposomes ranged from 90 to 100nm with low polydispersity index (<0.5). The entrapment efficiency of optimized liposomes was between 50 and 60%, functionalized liposomes showed maximum entrapment. The TEM images showed predominantly spherical vesicles with smooth bilayered surface. All formulations showed prolonged diffusion controlled drug release. The in vivo results showed that liposomal formulations provided enhanced brain exposure. Among the formulations studied, PEGylated liposomes (LP-16) had shown greater uptake of risperidone into the brain than plasma. High brain targeting efficiency index for LP-16 indicating preferential transport of the drug to brain. The study demonstrated successful formulation of surface modified risperidone liposomes for nasal delivery with brain targeting potential. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Liposome/water lipophilicity: methods, information content, and pharmaceutical applications.

    PubMed

    van Balen, Georgette Plemper; Martinet, Catherine a Marca; Caron, Giulia; Bouchard, Géraldine; Reist, Marianne; Carrupt, Pierre-Alain; Fruttero, Roberta; Gasco, Alberto; Testa, Bernard

    2004-05-01

    This review discusses liposome/water lipophilicity in terms of the structure of liposomes, experimental methods, and information content. In a first part, the structural properties of the hydrophobic core and polar surface of liposomes are examined in the light of potential interactions with solute molecules. Particular emphasis is placed on the physicochemical properties of polar headgroups of lipids in liposomes. A second part is dedicated to three useful methods to study liposome/water partitioning, namely potentiometry, equilibrium dialysis, and (1)H-NMR relaxation rates. In each case, the principle and limitations of the method are discussed. The next part presents the structural information encoded in liposome/water lipophilicity, in other words the solutes' structural and physicochemical properties that determine their behavior and hence their partitioning in such systems. This presentation is based on a comparison between isotropic (i.e., solvent/water) and anisotropic (e.g., liposome/water) systems. An important factor to be considered is whether the anisotropic lipid phase is ionized or not. Three examples taken from the authors' laboratories are discussed to illustrate the factors or combinations thereof that govern liposome/water lipophilicity, namely (a) hydrophobic interactions alone, (b) hydrophobic and polar interactions, and (c) conformational effects plus hydrophobic and ionic interactions. The next part presents two studies taken from the field of QSAR to exemplify the use of liposome/water lipophilicity in structure-disposition and structure-activity relationships. In the conclusion, we summarize the interests and limitations of this technology and point to promising developments.

  1. RGD-TPGS decorated theranostic liposomes for brain targeted delivery.

    PubMed

    Sonali; Singh, Rahul Pratap; Sharma, Gunjan; Kumari, Lakshmi; Koch, Biplob; Singh, Sanjay; Bharti, Shreekant; Rajinikanth, Paruvathanahalli Siddalingam; Pandey, Bajarangprasad L; Muthu, Madaswamy S

    2016-11-01

    The aim of this work was to formulate RGD-TPGS decorated theranostic liposomes, which contain both docetaxel (DTX) and quantum dots (QDs) for brain cancer imaging and therapy. RGD conjugated TPGS (RGD-TPGS) was synthesized and conjugation was confirmed by Fourier transform infrared (FTIR) spectroscopy and electrospray ionisation (ESI) mass spectroscopy (ESI-MS). The theranostic liposomes were prepared by the solvent injection method and characterized for their particle size, polydispersity, zeta-potential, surface morphology, drug encapsulation efficiency, and in-vitro release study. Biocompatibility and safety of theranostic liposomes were studied by reactive oxygen species (ROS) generation study and histopathology of brain. In-vivo study was performed for determination of brain theranostic effects in comparison with marketed formulation (Docel™) and free QDs. The particle sizes of the non-targeted and targeted theranostic liposomes were found in between 100 and 200nm. About 70% of drug encapsulation efficiency was achieved with liposomes. The drug release from RGD-TPGS decorated liposomes was sustained for more than 72h with 80% of drug release. The in-vivo results demonstrated that RGD-TPGS decorated theranostic liposomes were 6.47- and 6.98-fold more effective than Docel™ after 2h and 4h treatments, respectively. Further, RGD-TPGS decorated theranostic liposomes has reduced ROS generation effectively, and did not show any signs of brain damage or edema in brain histopathology. The results of this study have indicated that RGD-TPGS decorated theranostic liposomes are promising carrier for brain theranostics. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Enzyme-containing liposomes can endogenously produce membrane-constituting lipids.

    PubMed

    Wick, R; Luisi, P L

    1996-04-01

    'Giant vesicles' are liposomes that have diameters of several micrometers. It is possible to microinject biochemicals into a single vesicle and follow the progress of a chemical reaction in real time by light microscopy. We have previously used this technique to inject phospholipase A2 into giant vesicles; the vesicles disappeared as their components were hydrolyzed. Here we investigate whether the lipid components of a vesicle can be synthesized inside it. Giant vesicles composed of 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (POPC) and palmitoyl-CoA were prepared in a solution containing sn-glycerol-3-phosphate. Microinjection of the enzyme sn-glycerol-3-phosphate-acyltransferase into the vesicle catalyzes the in situ production of the lipid membrane precursor 1-palmitoyl-sn-glycerol-3-phosphate, which remains incorporated in the membrane. The altered membrane chemistry causes shrinkage of the vesicle and formation of smaller liposomes on the inner surface at the site of injection. Similar transformations were seen when the enzyme was added to the outside of the vesicle. We have used the first step of the 'salvage pathway' for synthesis of POPC to demonstrate that it is possible to localize the synthesis of a lipid membrane precursor inside a giant vesicle. In the future it may be possible to combine the necessary enzymes and substrates to carry out the reactions for a complete metabolic pathway within a liposome.

  3. Liposome aggregation in presence of the sweeteners cyclamate and saccharine.

    PubMed

    Hianik, T; Rybár, P; Svobodová, L; Kresák, S; Nikolelis, D P

    2001-08-01

    The interaction of the sweeteners saccharine and cyclamate with large unilamellar liposomes and planar bilayer lipid membranes (BLM) was studied. Application of the methods of light scattering and sound velocimetry showed that saccharine induces aggregation of liposomes, while cyclamate probably caused increase of the hydration of liposome surface. The sweeteners induced changes of BLM compressibility in a direction perpendicular to the membrane plane. The cyclamate induced considerably larger decreases in the elasticity module than saccharine. The obtained results show that both saccharine and cyclamate interacts with the surface of lipid bilayer and could modify the physical properties of lipid membranes.

  4. Liposome production by microfluidics: potential and limiting factors

    PubMed Central

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

    2016-01-01

    This paper provides an analysis of microfluidic techniques for the production of nanoscale lipid-based vesicular systems. In particular we focus on the key issues associated with the microfluidic production of liposomes. These include, but are not limited to, the role of lipid formulation, lipid concentration, residual amount of solvent, production method (including microchannel architecture), and drug loading in determining liposome characteristics. Furthermore, we propose microfluidic architectures for the mass production of liposomes with a view to potential industrial translation of this technology. PMID:27194474

  5. Liposomal Drug Products: A Quality by Design Approach

    NASA Astrophysics Data System (ADS)

    Xu, Xiaoming

    Quality by Design (QbD) principles has been applied to the development of two liposomal formulations, containing a hydrophilic small molecule therapeutic (Tenofovir) and a protein therapeutic (superoxide dismutase). The goal of the research is to provide critical information on 1) how to reduce the preparation variability in liposome formulations, and 2) how to increase drug encapsulation inside liposomes to reduce manufacturing cost. Most notably, an improved liposome preparation method was developed which increased the encapsulation efficiency of hydrophilic molecules. In particular, this method allows for very high encapsulation efficiency. For example, encapsulation efficiencies of up to 50% have been achieved, whereas previously only 20% or less have been reported. Another significant outcome from this research is a first principle mathematical model to predict the encapsulation efficiency of hydrophilic drugs in unilamellar liposomes. This mathematical model will be useful in: formulation development to rapidly achieve optimized formulations; comparison of drug encapsulation efficiencies of liposomes prepared using different methods; and assisting in the development of suitable process analytical technologies to achieve real-time monitoring and control of drug encapsulation during manufacturing. A novel two-stage reverse dialysis in vitro release testing method has also been developed for passively targeted liposomes, which uses the first stage to mimic the circulation of liposomes in the body and the second stage to imitate the drug release process at the target. The developed in vitro release testing method can be used to distinguish formulations with varied compositions for quality control testing purposes. This developed method may pave the way to the development of more biorelevant quality control testing methods for liposomal drug products in the future. The QbD case studies performed in this research are examples of how this approach can be used to

  6. pH-Sensitive Liposomes: Possible Clinical Implications

    NASA Astrophysics Data System (ADS)

    Yatvin, M. B.; Kreutz, W.; Horwitz, B. A.; Shinitzky, M.

    1980-12-01

    When pH-sensitive molecules are incorporated into liposomes, drugs can be specifically released from these vesicles by a change of pH in the ambient serum. Liposomes containing the pH-sensitive lipid palmitoyl homocysteine (PHC) were constructed so that the greatest pH differential (6.0 to 7.4) of drug release was obtained near physiological temperature. Such liposomes could be useful clinically if they enable drugs to be targeted to areas of the body in which pH is less than physiological, such as primary tumors and metastases or sites of inflammation and infection.

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

    PubMed Central

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

    2013-01-01

    Solar radiation causes damage to human skin, and photoprotection is the main way to prevent these harmful effects. The development of sunscreen formulations containing nanosystems is of great interest in the pharmaceutical and cosmetic industries because of the many potential benefits. This study aimed to develop and evaluate an octyl methoxycinnamate (OMC) liposomal nanosystem (liposome/OMC) to obtain a sunscreen formulation with improved safety and efficacy by retaining OMC for longer on the stratum corneum. 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 the HET-CAM test, indicating good histocompatibility. The formulation containing liposome/OMC had a higher in vivo solar photoprotection factor, but did not show increased water resistance. Inclusion in liposomes was able to slow down the release of OMC from the formulation, with a lower steady-state flux (3.9 ± 0.33 μg/cm2/hour) compared with the conventional formulation (6.3 ± 1.21 μg/cm2/hour). The stripping method showed increased uptake of OMC in the stratum corneum, giving an amount of 22.64 ± 7.55 μg/cm2 of OMC, which was higher than the amount found for the conventional formulation (14.57 ± 2.30 μg/cm2

  8. Studies on precellular evolution - The encapsulation of polyribonucleotides by liposomes

    NASA Technical Reports Server (NTRS)

    Baeza, I.; Ibanez, M.; Santiago, J. C.; Wong, C.; Lazcano, A.

    1986-01-01

    Liposomes have been suggested as possible models of precellular systems formed in the early Archean earth from lipids of nonenzymatic origin. Since it is generally accepted that RNA molecules preceded double-stranded DNA molecules as genetic material, the encapsulation of polyribonucleotides within liposomes (made from dipalmitoyl phosphatidylcholine and from egg yolk phosphatidylcholine) was studied. Quantitative determinations show that approximately 50 percent of the available lipids form liposomes, and that up to 5 percent of the polyribonucleotides can be entrapped by them. Also studied was the encapsulation of polyribonucleotides in the presence of urea and cyanamide and of Zn(2+) and Pb(2+).

  9. Enhanced liposome-mediated activity of piperacillin against staphylococci.

    PubMed Central

    Nacucchio, M C; Bellora, M J; Sordelli, D O; D'Aquino, M

    1985-01-01

    This study showed that encapsulation of the beta-lactam antibiotic piperacillin (PIP) by liposomes prepared with phosphatidylcholine and cholesterol (1:1) protected the drug from hydrolysis by staphylococcal beta-lactamase. This was demonstrated by growth inhibition of Staphylococcus aureus in the presence of the liposomal preparation containing PIP at a 50% MIC. Growth inhibition was also seen when exogenous beta-lactamase was added. Furthermore, adsorption of PIP onto the surface of liposomes containing buffer conferred a significant degree of protection against enzymatic hydrolysis of the drug, thus enhancing its antistaphylococcal activity. PMID:3872624

  10. Application of liposomes in medicine and drug delivery.

    PubMed

    Daraee, Hadis; Etemadi, Ali; Kouhi, Mohammad; Alimirzalu, Samira; Akbarzadeh, Abolfazl

    2016-01-01

    Liposomes provide an established basis for the sustainable development of different commercial products for treatment of medical diseases by the smart delivery of drugs. The industrial applications include the use of liposomes as drug delivery vehicles in medicine, adjuvants in vaccination, signal enhancers/carriers in medical diagnostics and analytical biochemistry, solubilizers for various ingredients as well as support matrices for various ingredients and penetration enhancers in cosmetics. In this review, we summarize the main applications and liposome-based commercial products that are currently used in the medical field.

  11. Targeted drug delivery and enhanced intracellular release using functionalized liposomes

    NASA Astrophysics Data System (ADS)

    Garg, Ashish

    The ability to target cancer cells using an appropriate drug delivery system can significantly reduce the associated side effects from cancer therapies and can help in improving the overall quality of life, post cancer survival. Integrin alpha5beta1 is expressed on several types of cancer cells, including colon cancer and plays an important role in tumor growth and metastasis. Thus, the ability to target the integrin alpha 5beta1 using an appropriate drug delivery nano-vector can significantly help in inhibiting tumor growth and reducing tumor metastasis. The work in this thesis focuses on designing and optimizing, functionalized stealth liposomes (liposomes covered with polyethylene glycol (PEG)) that specifically target the integrin alpha5beta1. The PEG provides a steric barrier allowing the liposomes to circulate in the blood for longer duration and the functionalizing moiety, PR_b peptide specifically recognizes and binds to integrin alpha5beta1 expressing cells. The work demonstrates that by optimizing the amount of PEG and PR_b on the liposomal interface, nano-vectors can be engineered that bind to CT26.WT colon cancer cells in a specific manner and internalize through alpha 5beta1-mediated endocytosis. To further improve the efficacy of the system, PR_b functionalized pH-sensitive stealth liposomes that exhibit triggered release under mild acidic conditions present in endocytotic vesicles were designed. The study showed that PR_b functionalized pH-sensitive stealth liposomes, undergo destabilization under mildly acidic conditions and incorporation of the PR_b peptide does not significantly affect the pH-sensitivity of the liposomes. PR_b functionalized pH-sensitive stealth liposomes bind to CT26.WT colon carcinoma cells that express integrin alpha5beta 1, undergo cellular internalization, and release their load intracellularly in a short period of time as compared to other formulations. PR_b-targeted pH-sensitive stealth liposomes encapsulating 5

  12. Novel tetrapeptide, RGDF, mediated tumor specific liposomal doxorubicin (DOX) preparations.

    PubMed

    Du, Huirui; Cui, Chunying; Wang, Lili; Liu, Hu; Cui, Guohui

    2011-08-01

    Arginine-glycine-aspartate (RGD) has been shown to possess a strong affinity for the integrins overexpressed in tumor cells, especially during tumor invasion, angiogenesis and metasis. Based on work from others, a novel tetrapeptide, arginine-glycine-aspartate-phenylanaline (RGDF), has been designed and studied as a homing device to direct liposomal doxorubicin (DOX) to tumor cells in this work. In order to incorporate RGDF into liposomal DOX preparations, RGDF was conjugated with three different fatty alcohols to achieve RGDF-fatty alcohol conjugates. Glycine-glycine-aspartate-phenylanaline (GGDF)-lauryl alcohol conjugate was synthesized as a negative control. RGDF-fatty alcohol conjugates (RGDFO(CH(2))(n)CH(3)) and GGDF-lauryl alcohol conjugate (L-GGDFC12-DOX) incorporated liposomal preparations were obtained by first preparing liposomes using the film dispersion method followed by loading DOX using a transmembrane pH gradient method. Because of their amphipathic nature, RGDF- or GGDF-fatty alcohol conjugates are expected to be readily incorporated into liposomes with their fatty alkanyl chains being intercalated between fatty acyl chains of liposomal bilayers and the hydrophilic peptide moiety (RGDF or GGDF) being anchored on the surface of liposomes. The particle size and zeta potential of liposomal DOX preparations containing RGDF-fatty alcohol conjugate (L-RGDF-DOXs) or L-GGDFC12-DOX were measured, and their morphology was studied using transmission electron microscopy. In vitro DOX release profile from RGDF incorporated liposomal DOX was measured. The antitumor activities of RGDF incorporated liposomal DOX preparations were evaluated in ICR mice inoculated with sarcoma S(180), which is known to express α(v)β(3) integrin. Both conventional liposomal DOX preparation (L-DOX) without RGDFO(CH(2))(n)CH(3) and L-GGDFC12-DOX were used as negative controls. Our results showed improved tumor growth inhibition with L-RGDF-DOXs over doxorubicin hydrochloride solution

  13. Mechanism of chemical degradation and determination of solubility by kinetic modeling of the highly unstable sesquiterpene lactone nobilin in different media.

    PubMed

    Thormann, Ursula; De Mieri, Maria; Neuburger, Markus; Verjee, Sheela; Altmann, Peter; Hamburger, Matthias; Imanidis, Georgios

    2014-10-01

    The objective of this work was first to investigate the chemical degradation of the sesquiterpene lactone nobilin and determine its solubility under conditions of concurrent degradation for partially amorphous starting material; second, to determine the effect of biorelevant media used in the in vitro measurement of intestinal absorption on degradation and solubility of nobilin. Purely aqueous medium (aq-TMCaco ), fasted and fed state simulated intestinal fluid (FaSSIF-TMCaco and FeSSIF-TMCaco ), and two liposomal formulations (LiposomesFaSSIF and LiposomesFeSSIF ) with the same lipid concentration as FaSSIF-TMCaco and FeSSIF-TMCaco were used. Degradation products were identified by nuclear magnetic resonance and X-ray crystallography and the order of reaction kinetics was determined. Solubility was deduced with a mathematical model encompassing dissolution, degradation, and reprecipitation kinetics that took into account particle size distribution of the solid material. Degradation mechanism of nobilin involved water-catalyzed opening of the lactone ring and transannular cyclization resulting in five degradation products. Degradation followed first-order kinetics in aq-TMCaco and FaSSIF-TMCaco , and higher-order kinetics in FeSSIF-TMCaco and the two liposomal formulations, whereas degradation in the latter media was diminished. Solubility of nobilin increased in the order: aq-TMCaco < FaSSIF-TMCaco , < LiposomesFaSSIF < FeSSIF-TMCaco < LiposomesFeSSIF . Improvement of stability and solubility was consistent with the incorporation of the nobilin molecule into colloidal lipid particles. The developed kinetic model is proposed to be a useful tool for deducing solubility under dynamic conditions. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

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

    PubMed Central

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

    2015-01-01

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

  15. Hsp90 Inhibitors Are Efficacious against Kaposi Sarcoma by Enhancing the Degradation of the Essential Viral Gene LANA, of the Viral Co-Receptor EphA2 as well as Other Client Proteins

    PubMed Central

    Chen, Wuguo; Sin, Sang-Hoon; Wen, Kwun Wah; Damania, Blossom; Dittmer, Dirk P.

    2012-01-01

    Heat-shock protein 90 (Hsp90) inhibitors exhibit activity against human cancers. We evaluated a series of new, oral bioavailable, chemically diverse Hsp90 inhibitors (PU-H71, AUY922, BIIB021, NVP-BEP800) against Kaposi sarcoma (KS). All Hsp90 inhibitors exhibited nanomolar EC50 in culture and AUY922 reduced tumor burden in a xenograft model of KS. KS is associated with KS-associated herpesvirus (KSHV). We identified the viral latency associated nuclear antigen (LANA) as a novel client protein of Hsp90 and demonstrate that the Hsp90 inhibitors diminish the level of LANA through proteasomal degradation. These Hsp90 inhibitors also downregulated EphA2 and ephrin-B2 protein levels. LANA is essential for viral maintenance and EphA2 has recently been shown to facilitate KSHV infection; which in turn feeds latent persistence. Further, both molecules are required for KS tumor formation and both were downregulated in response to Hsp90 inhibitors. This provides a rationale for clinical testing of Hsp90 inhibitors in KSHV-associated cancers and in the eradication of latent KSHV reservoirs. PMID:23209418

  16. Physicochemical characterization of asulacrine towards the development of an anticancer liposomal formulation via active drug loading: stability, solubility, lipophilicity and ionization.

    PubMed

    See, Esther; Zhang, Wenli; Liu, Jianping; Svirskis, Darren; Baguley, Bruce C; Shaw, John P; Wang, Guangji; Wu, Zimei

    2014-10-01

    To facilitate the development of a liposomal formulation for cancer therapy, the physicochemical properties of asulacrine (ASL), an anticancer drug candidate, were characterized. Nano-liposomes were prepared by thin-film hydration in conjugation with active drug loading using ammonium sulphate and post-insertion with Poloxamer 188. A stability-indicating HPLC assay with diode array detection was developed for the determination of ASL concentrations. The U-shaped pH-solubility profile in aqueous solutions, with a lowest solubility at pH 7.4 (0.843 μg/mL), indicated that ASL is an ampholyte, and dilution or neutralization of acidic drug solutions used in clinical trials with physiological fluids may cause drug precipitation. The basic pKa value measured by absorbance spectroscopy was 6.72. The logD value at pH 3.8 was 1.15 which increased to 3.24 as pH increased to 7.4. ASL was found to be the most stable in acidic conditions and degraded most rapidly in alkaline conditions. An extra-liposomal pH of 5.6 during drug loading was found to be optimal to achieve the highest drug loading (DL) of 4.76% and entrapment efficiency (EE) of 99.9%. At this pH, >90% of ASL was ionized conferring high drug solubility (1mg/mL) and acted as a reservoir of unionized ASL to be transported into liposomal cores. As a suspension the optimized liposomes showed great physicochemical stability for five months at 4°C. In summary, the obtained physicochemical parameters provided insightful information useful to maximise DL into the liposomes, and explain a tendency of drug precipitation of pH-solubilized formulations following intravenous infusion. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Formulation, characterization and tissue distribution of a novel pH-sensitive long-circulating liposome-based theranostic suitable for molecular imaging and drug delivery

    PubMed Central

    Duan, Yin; Wei, Lihui; Petryk, Julia; Ruddy, Terrence D

    2016-01-01

    Purpose When designing liposome formulas for treatment and diagnostic purposes, two of the most common challenges are 1) the lack of a specific release mechanism for the encapsulated contents and 2) a short circulation time due to poor resistance to biological fluids. This study aimed to create a liposome formula with prolonged in vivo longevity and pH-sensitivity for cytoplasmic drug delivery. Materials and methods Liposomal particles were generated using hydrogenated soy (HS) phosphatidylcholine, cholesteryl hemisuccinate (CHEM), polyethylene glycol (PEG) and diethylenetriaminepentaacetic acid-modified phosphatidylethanolamine with film hydration and extrusion methods. The physicochemical properties of the different formulas were characterized. pH-sensitivity was evaluated through monitoring release of encapsulated calcein. Stability of the radiolabeled liposomes was assessed in vitro through incubation with human serum. The best formula was selected and injected into healthy rats to assess tissue uptake and pharmacokinetics. Results Liposomal particles were between 88 and 102 nm in diameter and negatively charged on the surface. Radiolabeling of all formulas with indium-111 was successful with good efficiency. 1%PEG-HS-CHEM not only responded to acidification very quickly but also underwent heavy degradation with serum. The 4%PEG-HS-CHEM, which exhibited both comparatively good pH-sensitivity (up to 20% release) and satisfactory stability (stability >70% after 24 h), was considered the best candidate for in vivo evaluation. Tissue distribution of 4%PEG-HS-CHEM was comparable to that of 4%PEG-HS-Chol, a long-circulating but pH-insensitive control, showing major accumulation in liver, spleen, intestine and kidneys. Analysis of blood clearance showed favorable half-life values: 0.6 and 14 h in fast and slow clearance phases, respectively. Conclusion 4%PEG-HS-CHEM showed promising results in pH-sensitivity, serum stability, tissue uptake and kinetics and is a novel

  18. Effects of the liposomal formulation on the behavior and physical characteristics of acoustic liposomes

    NASA Astrophysics Data System (ADS)

    Sax, Nicolas; Horie, Sachiko; Li, Li; Sakamoto, Maya; Mori, Shiro; Kodama, Tetsuya

    2012-09-01

    Ultrasound contrast agents (UCAs) are nano/microbubbles that contain air or a highmolecular-weight, low-solubility gas encapsulated in a lipid or albumin shell. Previous studies have developed acoustic liposomes (ALs), liposomes that encapsulate perfluoropropane (C3F8) gas. These ALs can be used as just UCAs, for early diagnostic or observation of angiogenesis. They can also be used for drug delivery, through their ultrasound-induced destruction leading to permeabilization of the neighboring cells. However, the echogenicity of ALs decreases within minutes, raising the need for more stable preparations. Here we show that the in vitro stability of ALs is affected by fluidity changes in the bilayer, the presence of anionic phospholipids and the density of the PEG coating layer. These results allowed the preparation of "optimized" ALs displaying a 50% enhanced detection time in vitro. We anticipate their stability to be enhanced in a similar manner, in vivo. Further research aims at further improvement of the stability of gas encapsulation by surface modification and coating of the liposomes, and in vivo characterization of the optimized ALs.

  19. The modulation of the permeability and the cellular uptake of liposome by stable anchoring of lipid-conjugated pluronic on liposome.

    PubMed

    Kim, Jong Chul; Chungt, Yong-Il; Kim, Young Ha; Tae, Giyoong

    2014-01-01

    Controlling the permeability of liposome is important to modulate the release behavior of drug from the liposome. Pluronic F127 (PF127) is a biocompatible tri-block copolymer, which can interact with lipid bilayer of liposomes and make leakages that allow the release of hydrophilic substance from liposome interior. However, the interaction between unmodified PF127 and lipid bilayer is not very strong and the incorporated PF127 is easily desorbed from the liposomes in an infinite reservoir condition. In this paper, we conjugated lipid molecule (1,2-distearoyl-sn-glycero-3-phosphoethanolamine [DSPE]) at the both ends of PF127 to increase the interaction between polymer and liposome. This lipid-conjugated PF127 was incorporated into the liposomes and it remained stably without desorption from liposomes in an infinite reservoir condition. The stably bound PF127 increased the release rate of hydrophilic drug from liposomes in a dose-dependent manner. Moreover, the lipid-conjugated PF127 changed the surface property of liposomes and inhibited its cellular uptake when the incorporated amount was above 2.5 wt%. In conclusion, the lipid-conjugated PF127 could function as a stable anchor on the lipid bilayer of liposomes to control the permeability as well as provide the hydrophilic surface of liposomes in an open system like an in vivo situation.

  20. Hydration of polyethylene glycol-grafted liposomes.

    PubMed Central

    Tirosh, O; Barenholz, Y; Katzhendler, J; Priev, A

    1998-01-01

    This study aimed to characterize the effect of polyethylene glycol of 2000 molecular weight (PEG2000) attached to a dialkylphosphatidic acid (dihexadecylphosphatidyl (DHP)-PEG2000) on the hydration and thermodynamic stability of lipid assemblies. Differential scanning calorimetry, densitometry, and ultrasound velocity and absorption measurements were used for thermodynamic and hydrational characterization. Using a differential scanning calorimetry technique we showed that each molecule of PEG2000 binds 136 +/- 4 molecules of water. For PEG2000 covalently attached to the lipid molecules organized in micelles, the water binding increases to 210 +/- 6 water molecules. This demonstrates that the two different structural configurations of the PEG2000, a random coil in the case of the free PEG and a brush in the case of DHP-PEG2000 micelles, differ in their hydration level. Ultrasound absorption changes in liposomes reflect mainly the heterophase fluctuations and packing defects in the lipid bilayer. The PEG-induced excess ultrasound absorption of the lipid bilayer at 7.7 MHz for PEG-lipid concentrations over 5 mol % indicates the increase in the relaxation time of the headgroup rotation due to PEG-PEG interactions. The adiabatic compressibility (calculated from ultrasound velocity and density) of the lipid bilayer of the liposome increases monotonically with PEG-lipid concentration up to approximately 7 mol %, reflecting release of water from the lipid headgroup region. Elimination of this water, induced by grafted PEG, leads to a decrease in bilayer defects and enhanced lateral packing of the phospholipid acyl chains. We assume that the dehydration of the lipid headgroup region in conjunction with the increase of the hydration of the outer layer by grafting PEG in brush configuration are responsible for increasing thermodynamic stability of the liposomes at 5-7 mol % of PEG-lipid. At higher PEG-lipid concentrations, compressibility and partial volume of the lipid phase

  1. Hydration of polyethylene glycol-grafted liposomes.

    PubMed

    Tirosh, O; Barenholz, Y; Katzhendler, J; Priev, A

    1998-03-01

    This study aimed to characterize the effect of polyethylene glycol of 2000 molecular weight (PEG2000) attached to a dialkylphosphatidic acid (dihexadecylphosphatidyl (DHP)-PEG2000) on the hydration and thermodynamic stability of lipid assemblies. Differential scanning calorimetry, densitometry, and ultrasound velocity and absorption measurements were used for thermodynamic and hydrational characterization. Using a differential scanning calorimetry technique we showed that each molecule of PEG2000 binds 136 +/- 4 molecules of water. For PEG2000 covalently attached to the lipid molecules organized in micelles, the water binding increases to 210 +/- 6 water molecules. This demonstrates that the two different structural configurations of the PEG2000, a random coil in the case of the free PEG and a brush in the case of DHP-PEG2000 micelles, differ in their hydration level. Ultrasound absorption changes in liposomes reflect mainly the heterophase fluctuations and packing defects in the lipid bilayer. The PEG-induced excess ultrasound absorption of the lipid bilayer at 7.7 MHz for PEG-lipid concentrations over 5 mol % indicates the increase in the relaxation time of the headgroup rotation due to PEG-PEG interactions. The adiabatic compressibility (calculated from ultrasound velocity and density) of the lipid bilayer of the liposome increases monotonically with PEG-lipid concentration up to approximately 7 mol %, reflecting release of water from the lipid headgroup region. Elimination of this water, induced by grafted PEG, leads to a decrease in bilayer defects and enhanced lateral packing of the phospholipid acyl chains. We assume that the dehydration of the lipid headgroup region in conjunction with the increase of the hydration of the outer layer by grafting PEG in brush configuration are responsible for increasing thermodynamic stability of the liposomes at 5-7 mol % of PEG-lipid. At higher PEG-lipid concentrations, compressibility and partial volume of the lipid phase

  2. Characterization of fatty acid liposome coated with low-molecular-weight chitosan.

    PubMed

    Tan, Hsiao Wei; Misran, Misni

    2012-12-01

    Preparation of chitosan-coated fatty acid liposomes is often restricted by the solubility of chitosan under basic conditions. In this experiment, the preparation of chitosan-coated oleic acid (OA) liposomes using low molecular weight (LMW) chitosan (10 and 25 kDA) was demonstrated. These selected LMW chitosans are water soluble. The coating of the chitosan layer on OA liposomes was confirmed by its microscope images and physicochemical properties, such as zeta potential and the size of the liposomes. The "peeling off" effect on the surface of chitosan-coated OA liposomes was observed in the atomic force microscope images and showed the occurrence of the chitosan layer on the surface of OA liposomes. The size of the chitosan-coated liposomes was at least 20 nm smaller than the OA liposomes, and the increase of zeta potential with the increasing amount of LMW chitosan further confirmed the presence of the surface modification of OA liposomes.

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

    PubMed

    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.

  4. Sustained distribution of aerosolized PEGylated liposomes in epithelial lining fluids on alveolar surfaces.

    PubMed

    Kaneko, Keita; Togami, Kohei; Yamamoto, Eri; Wang, Shujun; Morimoto, Kazuhiro; Itagaki, Shirou; Chono, Sumio

    2016-10-01

    The distribution characteristics of aerosolized PEGylated liposomes in alveolar epithelial lining fluid (ELF) were examined in rats, and the ensuing mechanisms were investigated in the in vitro uptake and protein adsorption experiments. Nonmodified or PEGylated liposomes (particle size 100 nm) were aerosolized into rat lungs. PEGylated liposomes were distributed more sustainably in ELFs than nonmodified liposomes. Furthermore, the uptake of PEGylated liposomes by alveolar macrophages (AMs) was less than that of nonmodified liposomes. In further in vitro uptake experiments, nonmodified and PEGylated liposomes were opsonized with rat ELF components and then added to NR8383 cells as cultured rat AMs. The uptake of opsonized PEGylated liposomes by NR8383 cells was lower than that of opsonized nonmodified liposomes. Moreover, the protein absorption levels in opsonized PEGylated liposomes were lower than those in opsonized nonmodified liposomes. These findings suggest that sustained distributions of aerosolized PEGylated liposomes in ELFs reflect evasion of liposomal opsonization with surfactant proteins and consequent reductions in uptake by AMs. These data indicate the potential of PEGylated liposomes as aerosol-based drug delivery system that target ELF for the treatment of respiratory diseases.

  5. Placing and shaping liposomes with reconfigurable DNA nanocages

    NASA Astrophysics Data System (ADS)

    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.

  6. Liposome surface charge influence on skin penetration behaviour.

    PubMed

    Gillet, A; Compère, P; Lecomte, F; Hubert, P; Ducat, E; Evrard, B; Piel, G

    2011-06-15

    Vesicular systems have shown their ability to increase dermal and transdermal drug delivery. Their mechanism of drug transport into and through the skin has been investigated but remains a much debated question. Several researchers have outlined that drug penetration can be influenced by modifying the surface charge of liposomes. In the present work we study the influence of particle surface charge on skin penetration. The final purpose is the development of a carrier system which is able to enhance the skin delivery of two model drugs, betamethasone and betamethasone dipropionate. Liposomes were characterised by their size, morphology, zeta potential, encapsulation efficiency and stability. Ex vivo diffusion studies using Franz diffusion cells were performed. Confocal microscopy was performed to visualise the penetration of fluorescently labelled liposomes into the skin. This study showed the potential of negatively charged liposomes to enhance the skin penetration of betamethasone and betamethasone dipropionate.

  7. Light activated liposomes: Functionality and prospects in ocular drug delivery.

    PubMed

    Lajunen, Tatu; Nurmi, Riikka; Kontturi, Leena; Viitala, Lauri; Yliperttula, Marjo; Murtomäki, Lasse; Urtti, Arto

    2016-12-28

    Ocular drug delivery, especially to the retina and choroid, is a major challenge in drug development. Liposome technology may be useful in ophthalmology in enabling new routes of delivery, prolongation of drug action and intracellular drug delivery, but drug release from the liposomes should be controlled. For that purpose, light activation may be an approach to release drug at specified time and site in the eye. Technical advances have been made in the field of light activated drug release, particularly indocyanine green loaded liposomes are a promising approach with safe materials and effective light triggered release of small and large molecules. This review discusses the liposomal drug delivery with light activated systems in the context of ophthalmic drug delivery challenges.

  8. Effect of Surface Properties on Liposomal siRNA Delivery

    PubMed Central

    Xia, Yuqiong; Tian, Jie; Chen, Xiaoyuan

    2015-01-01

    Liposomes are one of the most widely investigated carriers for siRNA delivery. The surface properties of liposomal carriers, including the surface charge, PEGylation, and ligand modification can significantly affect the gene silencing efficiency. Three barriers of systemic siRNA delivery (long blood circulation, efficient tumor penetration and efficient cellular uptake/endosomal escape) are analyzed on liposomal carriers with different surface charges, PEGylations and ligand modifications. Cationic formulations dominate siRNA delivery and neutral formulations also have good performance while anionic formulations are generally not proper for siRNA delivery. The PEG dilemma (prolonged blood circulation vs. reduced cellular uptake/endosomal escape) and the side effect of repeated PEGylated formulation (accelerated blood clearance) were discussed. Effects of ligand modification on cationic and neutral formulations were analyzed. Finally, we summarized the achievements in liposomal siRNA delivery, outlined existing problems and provided some future perspectives. PMID:26695117

  9. Liposomal amphotericin B in neonates with invasive candidiasis.

    PubMed

    Al Arishi, H; Frayha, H H; Kalloghlian, A; Al Alaiyan, S

    1998-01-01

    Liposomal amphotericin B (L-Amp B), a novel formulation of amphotericin B, is effective for the treatment of invasive fungal infections in children and adults and is associated with less toxicity than the conventional preparation. Data on the use of Liposomal amphotericin B in neonates is scarce. We describe the clinical course of two premature infants who were treated with Liposomal amphotericin B (one infant had candidemia, and the other had candidemia and meningitis), and provide a summary of previously published experience on this topic. Liposomal amphotericin B may be an option for therapy of invasive candidiasis in neonates who are at high risk of nephrotoxicity and other amphotericin-related reactions, but clinical trials are necessary to document its safety and efficacy in this age group.

  10. Effect of surface properties on liposomal siRNA delivery.

    PubMed

    Xia, Yuqiong; Tian, Jie; Chen, Xiaoyuan

    2016-02-01

    Liposomes are one of the most widely investigated carriers for siRNA delivery. The surface properties of liposomal carriers, including the surface charge, PEGylation, and ligand modification can significantly affect the gene silencing efficiency. Three barriers of systemic siRNA delivery (long blood circulation, efficient tumor penetration and efficient cellular uptake/endosomal escape) are analyzed on liposomal carriers with different surface charges, PEGylations and ligand modifications. Cationic formulations dominate siRNA delivery and neutral formulations also have good performance while anionic formulations are generally not proper for siRNA delivery. The PEG dilemma (prolonged blood circulation vs. reduced cellular uptake/endosomal escape) and the side effect of repeated PEGylated formulation (accelerated blood clearance) were discussed. Effects of ligand modification on cationic and neutral formulations were analyzed. Finally, we summarized the achievements in liposomal siRNA delivery, outlined existing problems and provided some future perspectives. Published by Elsevier Ltd.

  11. Real-time observation of liposome bursting induced by acetonitrile.

    PubMed

    Yoshida, Kazunari; Horii, Keitaro; Fujii, Yasuhiro; Nishio, Izumi

    2014-10-06

    We show the bursting process of dioleoylphosphatidylcholine (DOPC) liposomes in response to the addition of acetonitrile, a small toxic molecule widely used in the fields of chemistry and industry. The percentage of destroyed liposomes is reduced upon decreasing the acetonitrile fraction in the aqueous solution and vesicle bursting is not observed at volume ratios of 4:6 and below. This indicates that a high fraction of acetonitrile causes the bursting of liposomes, and it is proposed that this occurs through insertion of the molecules into outer leaflet of the lipid bilayer. The elapsed time between initial addition of acetonitrile and liposome bursting at each vesicle is also measured and demonstrated to be dependent on the volume fraction of acetonitrile and the vesicle size.

  12. Atmospheric-pressure guided streamers for liposomal membrane disruption

    SciTech Connect

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

    2012-12-24

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

  13. Sonication-Based Basic Protocol for Liposome Synthesis.

    PubMed

    Mendez, Roberto; Banerjee, Santanu

    2017-01-01

    Liposomes are spherical vesicles with a wide range of sizes from nano- to micrometer scale. For the past 7-8 decades, these vesicles have occupied the interest of a variety of scientists due to its physical, chemical, and mathematical properties and, to say the least, for its immense utility and potential as delivery vehicles for toxic and nontoxic excipients into biological tissues. Methods related to selection of reagents for creation of specific liposomes of certain properties are beyond the scope of this chapter, but here, we would outline a simplistic protocol to prepare and qualify an uniform batch of simple liposome with basic cargo. This chapter will attempt to provide the reader with a starting point for this immensely potent tool to build upon the right kind of liposome, appropriate for their studies.

  14. Utilization of liposomes for studying drug transfer and uptake.

    PubMed

    Fahr, Alfred; Liu, Xiangli

    2010-01-01

    On entry into the body of the patient, drugs have to overcome many barriers in order to reach the target. The knowledge of the ability of drugs to cross these barriers, which mostly consist of lipid membranes, is of utmost interest in pharmacy.High values of lipophilicity of a drug might be a good pre-requisite for crossing these barriers. It also led liposomologists to think that highly lipophilic drugs may "stick" in the lipophilic interior of liposomal phospholipid membranes and therefore these liposomes may act as a retard formulation of the lipophilic drug.The presented method here estimates the transfer time of lipophilic drugs between liposomal lipid bilayers. This may help to judge the presumed retardation function of a specific liposomal delivery system for a chosen lipophilic drug.

  15. Liposomal delivery of boron to tumors for BNCT

    SciTech Connect

    Hawthorne, M.F.; Feakes, D.A.; Shelly, K.

    1994-12-31

    Results are reported on the use of liposomes to encapsulate boron containing compounds for use as a delivery vehicle to tumors. An increase in injected dose to the tumor in mammary glands of mice was realized.

  16. Bioreactor droplets from liposome-stabilized all-aqueous emulsions

    NASA Astrophysics Data System (ADS)

    Dewey, Daniel C.; Strulson, Christopher A.; Cacace, David N.; Bevilacqua, Philip C.; Keating, Christine D.

    2014-08-01

    Artificial bioreactors are desirable for in vitro biochemical studies and as protocells. A key challenge is maintaining a favourable internal environment while allowing substrate entry and product departure. We show that semipermeable, size-controlled bioreactors with aqueous, macromolecularly crowded interiors can be assembled by liposome stabilization of an all-aqueous emulsion. Dextran-rich aqueous droplets are dispersed in a continuous polyethylene glycol (PEG)-rich aqueous phase, with coalescence inhibited by adsorbed ~130-nm diameter liposomes. Fluorescence recovery after photobleaching and dynamic light scattering data indicate that the liposomes, which are PEGylated and negatively charged, remain intact at the interface for extended time. Inter-droplet repulsion provides electrostatic stabilization of the emulsion, with droplet coalescence prevented even for submonolayer interfacial coatings. RNA and DNA can enter and exit aqueous droplets by diffusion, with final concentrations dictated by partitioning. The capacity to serve as microscale bioreactors is established by demonstrating a ribozyme cleavage reaction within the liposome-coated droplets.

  17. Precipitation in liposomes as a model for intracellular biomineralization.

    PubMed

    Tester, Chantel C; Joester, Derk

    2013-01-01

    Liposomes present a versatile platform to model intracellular, biologically controlled mineralization. Perhaps, most importantly, precipitation in the confinement of liposomes excludes heterogeneous nucleators that facilitate formation of the thermodynamically most stable crystalline phase in bulk. This provides access to metastable amorphous precursors even in the absence of other additives that interact strongly with the mineral and is fundamental to the capability of cells to prevent spurious nucleation and to select a specific polymorph. Herein, we summarize methods to prepare liposomes from the nanometer to micron length scale and review strategies to carry out precipitation reactions of iron oxide, calcium carbonate, and calcium phosphate in the confinement of such liposomes. In addition, we discuss methods to characterize the morphology, structure, and growth kinetics of crystalline and amorphous precipitates, with particular emphasis on in situ characterization approaches. © 2013 Elsevier Inc. All rights reserved.

  18. Liposomes with polyribonucleotides as model of precellular systems

    NASA Technical Reports Server (NTRS)

    Baeza, Isabel; Ibanez, Miguel; Santiago, Carlos; Lazcano, Antonio; Arguello, Carlos

    1987-01-01

    Three types of liposomes were prepared under anoxic conditions: from dipalmitoyl phosphatidyl choline (DPPC), from egg yolk phosphatidyl choline (PC), and from PC with cholesterol (PC:Chol). These were used for encapsulation of poly(U) and poly(C). It was found that 36 to 70 percent of the available liposome lipids and 2 to 5 percent of the polyribonucleotides could be entrapped. An enhanced encapsulation of poly(U) and poly(C) by all three types of liposomes was observed in the presence of 0.001 to 0.01 M Zn(2+), with the effect being greatest with DPPC. The presence of 1.0 M urea inhibited the formation of PC liposomes.

  19. Placing and shaping liposomes with reconfigurable DNA nanocages.

    PubMed

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

    2017-06-23

    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.

  20. Liposomes with polyribonucleotides as model of precellular systems

    NASA Technical Reports Server (NTRS)

    Baeza, Isabel; Ibanez, Miguel; Santiago, Carlos; Lazcano, Antonio; Arguello, Carlos

    1987-01-01

    Three types of liposomes were prepared under anoxic conditions: from dipalmitoyl phosphatidyl choline (DPPC), from egg yolk phosphatidyl choline (PC), and from PC with cholesterol (PC:Chol). These were used for encapsulation of poly(U) and poly(C). It was found that 36 to 70 percent of the available liposome lipids and 2 to 5 percent of the polyribonucleotides could be entrapped. An enhanced encapsulation of poly(U) and poly(C) by all three types of liposomes was observed in the presence of 0.001 to 0.01 M Zn(2+), with the effect being greatest with DPPC. The presence of 1.0 M urea inhibited the formation of PC liposomes.

  1. Liposomal Packaging Generates Wnt Protein with In Vivo Biological Activity

    PubMed Central

    Zhao, Ludan; Kim, Jae-Beom; ten Berge, Derk; Ponnusamy, Karthik; Carre, A. Lyonel; Dudek, Henryk; Zachlederova, Marie; McElhaney, Michael; Brunton, Shirley; Gunzner, Janet; Callow, Marinella; Polakis, Paul; Costa, Mike; Zhang, Xiaoyan M.; Helms, Jill A.; Nusse, Roel

    2008-01-01

    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. PMID:18698373

  2. Potential utility of liposome bupivacaine in orthopedic surgery.

    PubMed

    Lonner, Jess H; Scuderi, Giles R; Lieberman, Jay R

    2015-03-01

    Management of postsurgical analgesia is an important consideration in orthopedic procedures, including joint arthroplasty. Inadequate postsurgical analgesia is associated with increased hospital length of stay, delayed ambulation, and reduced exercise capacity. In this article, we review the potential contribution of a prolonged-release liposomal formulation of bupivacaine as part of a multimodal analgesic regimen after orthopedic surgery. Controlled studies across multiple surgical settings have demonstrated that, compared with placebo and bupivacaine HCl, liposome bupivacaine in a single administration provides postsurgical analgesia for up to 72 hours, delays use of rescue medication, and reduces postsurgical opioid consumption. Liposome bupivacaine has been well tolerated in clinical studies and has had a low rate of treatment-related adverse events. To date, there has been no signal of cardiac toxicity, chondrolysis, or delayed wound healing associated with liposome bupivacaine.

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

    PubMed

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

    2012-06-06

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

  4. Interaction of isopropylthioxanthone with phospholipid liposomes.

    PubMed

    Momo, Federico; Fabris, Sabrina; Stevanato, Roberto

    2007-04-01

    Isopropylthioxanthone (ITX) is a highly lipophilic molecule which can be released in foods and beverages from the packages, where it is present as photoinitiator of inks in printing processes. Recently it was found in babies milk, and its toxicity cannot be excluded. The structure of the molecule suggests a possible strong interaction with the lipid moiety of biological membranes, and this is the first study of its effects on phospholipid organization, using differential scanning calorimetry (DSC) and spin labelling techniques. The data obtained with multilamellar liposomes of saturated phospholipids of different length, with and without cholesterol, point out that the molecule changes the lipid structure; in particular, in the gel state, behaving like a disordering agent it increases the mobility of the bilayer, while, in the fluid state, tends to rigidify the membrane, in a cholesterol like way. This behavior supports the hypothesis that ITX experiences a relocation process when the lipid matrix passes from the gel to the fluid state.

  5. Cerebrovascular Involvement in Liposome - Induced Cardiopulmonary Distress in Pigs

    DTIC Science & Technology

    2005-01-01

    expressed as mean ± SD. There was no statistical treament for data on the 24 pigs (Table 1); only percentage values were calculated. All applied...new, promising field for use of liposomes as a vehicle is in the treatment of cerebrovascular disease through gene therapy (Saito et al., 2004; Shi...brain by means of liposomes. Tohoku J. Exp. Med. 136:219-229. Toyoda, K., Chu, Y., Heistad, D. D. (2003). Gene therapy for cerebral vascular disease

  6. Calcium phosphate formation in aqueous suspensions of multilamellar liposomes.

    PubMed

    Eanes, E D; Hailer, A W; Costa, J L

    1984-07-01

    The present study examined calcium phosphate precipitation in aqueous suspensions of multilamellar liposomes as a possible in vitro model for matrix vesicle mineralization. Liposomes were prepared by dispersing CHCl3-evaporated thin films of 7:2:1 and 7:1:1 molar mixtures of phosphatidylcholine, dicetyl phosphate, and cholesterol in aqueous solutions containing 0, 25, or 50 mM PO4 and 0 or 0.8 mM Mg. After removal of unencapsulated PO4 by gel filtration, the liposomes were suspended in 1.33 mM Ca/0.8 mM Mg solutions and made permeable to these cations by the addition of the ionophore X-537A. All experiments were carried out at pH 7.4, 22 degrees C, and 240 mOsm. In the absence of entrapped PO4, Ca2+ taken up by the liposomes was largely bound to inner membrane surfaces. With PO4 present, Ca2+ uptake increased as much as sixfold with maximum accumulations well above values sufficient for solid formation. Precipitated solids appeared to be located predominantly in the aqueous intermembranous spaces of the liposomes. Amorphous calcium phosphate (ACP) precipitated initially in the presence of entrapped Mg2+, then subsequently converted to apatite intermixed with some octacalcium phosphate. The stability of the liposomal ACP was somewhat greater than that observed in bulk solutions under comparable conditions of pH, temperature, and electrolyte makeup. In time, the mineral deposits caused entrapped PO4 to leak from the liposomes. These findings suggest that the precipitation within liposomes is similar to that which occurs in macro-volume synthetic systems but that the precipitated solid eventually impairs the integrity of the surrounding intermembranous space.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Hyaluronic acid-coated liposomes for active targeting of gemcitabine.

    PubMed

    Arpicco, Silvia; Lerda, Carlotta; Dalla Pozza, Elisa; Costanzo, Chiara; Tsapis, Nicolas; Stella, Barbara; Donadelli, Massimo; Dando, Ilaria; Fattal, Elias; Cattel, Luigi; Palmieri, Marta

    2013-11-01

    The aim of this work was the preparation, characterization, and preliminary evaluation of the targeting ability toward pancreatic adenocarcinoma cells of liposomes containing the gemcitabine lipophilic prodrug [4-(N)-lauroyl-gemcitabine, C12GEM]. Hyaluronic acid (HA) was selected as targeting agent since it is biodegradable, biocompatible, and can be chemically modified and its cell surface receptor CD44 is overexpressed on various tumors. For this purpose, conjugates between a phospholipid, the 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), and HA of two different low molecular weights 4800 Da (12 disaccharidic units) and 12,000 Da (32 disaccharidic units), were prepared, characterized, and introduced in the liposomes during the preparation. Different liposomal formulations were prepared and their characteristics were analyzed: size, Z potential, and TEM analyses underline a difference in the HA-liposomes from the non-HA ones. In order to better understand the HA-liposome cellular localization and to evaluate their interaction with CD44 receptor, confocal microscopy studies were performed. The results demonstrate that HA facilitates the recognition of liposomes by MiaPaCa2 cells (CD44(+)) and that the uptake increases with increase in the polymer molecular weight. Finally, the cytotoxicity of the different preparations was evaluated and data show that incorporation of C12GEM increases their cytotoxic activity and that HA-liposomes inhibit cell growth more than plain liposomes. Altogether, the results demonstrate the specificity of C12GEM targeting toward CD44-overexpressing pancreatic adenocarcinoma cell line using HA as a ligand.

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

    PubMed

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

    2009-01-01

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

  9. Liposome-coated quantum dots targeting the sentinel lymph node

    NASA Astrophysics Data System (ADS)

    Chu, Maoquan; Zhuo, Shu; Xu, Jiang; Sheng, Qiunan; Hou, Shengke; Wang, Ruifei

    2010-01-01

    Sentinel lymph node (SLN) mapping with near-infrared (NIR) quantum dot (QDs) have many advantages over traditional methods. However, as an inorganic nanomaterial, QDs have low biocompatibility and low affinity to the lymphatic system. Here, we encapsulated QDs into nanoscale liposomes and then used these liposome-coated QDs for SLN mapping. The results showed that the liposome-coated QDs exhibited core-shell characterization, and their fluorescence emission did not decrease but slightly increased after being continuously excited by a xenon lamp source (150 W) at 488 nm at 37 °C for 1 h. After storing at 4 °C for more than one and half years, the liposome-coated QDs were found to have retained their spherical structure containing a large amount of QDs. When liposome-coated QDs with average size of 55.43 nm were injected intradermally into the paw of a mouse, the SLN was strongly fluorescent within only a few seconds and visualized easily in real time. Moreover, the fluorescence of the QDs trapped in the SLN could be observed for at least 24 h. Compared with the SLN mapping of QDs absent of liposomes and liposome-coated QDs with a larger average size (100.3 and 153.6 nm), more QDs migrated into the SLN when the liposome-coated QDs with smaller average size (55.43 nm) were injected. This technique may make a great contribution to the improvement of the biocompatibility of QDs and the targeting delivery capacity of QDs into the SLN.

  10. Photosensitive liposomes as potential drug delivery vehicles for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Morgan, Christopher G.; Mitchell, A. C.; Chowdhary, R. K.

    1991-11-01

    Light-sensitive liposomes incorporating a photochromic phospholipid (Bis-Azo PC) have been developed which exhibit light-activated release of entrapped contents and intervesicular fusion. The trapping and light-induced release of inorganic ions, fluorescent market dyes, and the antitumor drug methotrexate have been demonstrated. These results are discussed together with some of the potential therapeutic applications of light-sensitive liposomes.

  11. Technology of Liposomal Tiosens, Cifelin and Lysomustin for Industrial Purposes

    NASA Astrophysics Data System (ADS)

    Sanarova, E. V.; Kotova, E. A.; Lantsova, A. V.

    2012-02-01

    This work is devoted to the development of national antineoplastic drug (Tiosens, Cifelin, Lysomustin) liposomal dosage form (LDF) circuit technology and their manufacturing technology. In modern oncology liposomes, which are hollow phospholipid vesicles, are used as delivery systems protected drugs from biodegradation, and healthy cells from the toxic effect of chemotherapeutic agents. The technology of their production is stretching and multistage. It is also necessary to give consideration a lot of factors that influence on the finished product quality.

  12. Potential of Liposomes for Enhancement of Oral Drug Absorption.

    PubMed

    Daeihamed, Marjan; Dadashzadeh, Simin; Haeri, Azadeh; Akhlaghi, Masoud Faghih

    2017-01-01

    Oral administration of medication is the first option when patient compliance is considered. However, many barriers face oral absorption of drugs that limit bioavailability in about 90% of therapeutic agents. Utilization of nanoparticulate drug delivery systems is a major strategy for increasing oral absorption. They can improve oral bioavailability through mechanisms such as protection of the drug in the GI tract, increasing cellular contact and residence time of the drug, protection of the drug from presystemic metabolism and efflux and increasing diffusion across the mucosal and epithelial layers. Liposomes are biocompatible carriers employed to improve oral bioavailability of drugs and in addition to the general advantages of nanocarriers for oral delivery, they offer benefits derived from their lipidic bilayer structure. They can better adhere to biomembranes, form mixed-micelle structures with bile salts to increase the solubility of poorly-soluble drugs and are suitable candidates for lymphatic uptake. They have been successful in improving oral bioavailability of a variety of compounds including peptide and proteins, hydrophilic and lipophilic drugs. Stability under GI conditions is the main concern for oral liposomes, however, promising approaches have been suggested to increase the stability of oral liposomes. These include: using appropriate lipid compositions, polymer coating, addition of stabilizing lipids to liposomal structures, preparation of double liposomes and proliposomes and some other innovative methods. The present review focuses on the role of liposomes in improving oral absorption of drugs, the problems encountered, and the types of liposomes designed to overcome these issues. Barriers to oral delivery will be discussed and examples of bioavailability enhancement upon encapsulation in various types of liposomes investigated. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Copper-64 labeled liposomes for imaging bone marrow.

    PubMed

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

    2016-12-01

    Bone marrow is the soft tissue compartment inside the bones made up of hematopoietic cells, adipocytes, stromal cells, phagocytic cells, stem cells, and sinusoids. While [(18)F]-FLT has been utilized to image proliferative marrow, to date, there are no reports of particle based positron emission tomography (PET) imaging agents for imaging bone marrow. We have developed copper-64 labeled liposomal formulation that selectively targets bone marrow and therefore serves as an efficient PET probe for imaging bone marrow. Optimized liposomal formulations were prepared with succinyl PE, DSPC, cholesterol, and mPEG-DSPE (69:39:1:10:0.1) with diameters of 90 and 140nm, and were doped with DOTA-Bn-DSPE for stable (64)Cu incorporation into liposomes. PET imaging and biodistribution studies with (64)Cu-labeled liposomes indicate that accumulation in bone marrow was as high as 15.18±3.69%ID/g for 90nm liposomes and 7.01±0.92%ID/g for 140nm liposomes at 24h post-administration. In vivo biodistribution studies in tumor-bearing mice indicate that the uptake of 90nm particles is approximately 0.89±0.48%ID/g in tumor and 14.22±8.07%ID/g in bone marrow, but respective values for Doxil® like liposomes are 0.83±0.49%ID/g and 2.23±1.00%ID/g. Our results indicate that our novel PET labeled liposomes target bone marrow with very high efficiency and therefore can function as efficient bone marrow imaging agents. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. The Mechanism of Formation of Lipid Tubules from Liposomes

    DTIC Science & Technology

    1988-01-01

    structures about 10 in diameter and as longt as hundreds of micrometers. To elucidate the nature of the conversion process. freeze fracture electron...microscopy was utilized to examine samples that were rapidly quenched during tubule fOrmation. Many transitional structures -Acre obserjed. typically...that form unusual tubular structures [1-61. tain trapped liposomes (Fig. 1). When liposomes The lecithin 1.2-bis( l.l2-tricosadiynoyl)-sn-gly- are

  15. Ultrasonic Activation of Thermally Sensitive Liposomes

    NASA Astrophysics Data System (ADS)

    Mylonopouloua, Eleonora; Arvanitisa, Costas D.; Bazan-Peregrinoa, Miriam; Arora, Manish; Coussios, Constantin C.

    2010-03-01

    Cancerous cells are known to be more vulnerable to mild hyperthermia than healthy cells, which can survive temperatures above 43° C for brief periods of time. Currently in phase III clinical trials for liver cancer, ThermoDox® (Celsion Corporation) is a drug delivery system containing doxorubicin, a common anti-cancer agent, encapsulated within a thermally sensitive liposome designed to release its contents above 39.5° C. Activation of such an agent with the use of HIFU, which can generate localized heating non-invasively, would combine the benefits of targeted chemotherapy and hyperthermia while minimizing undesirable systemic side-effects. To that end, the resolution and reliability with which HIFU-induced hyperthermia can achieve Thermodox® release was investigated using a novel agar-based gel embedding liposomes at clinically relevant concentrations (0.02 mg/ml). The gel was exposed to 1.15 MHz HIFU (Sonic Concepts H102) using a range of clinically relevant pressure amplitudes (0-6 MPa peak rarefactional), duty cycles (10-100%) and exposure durations to identify optimal insonation conditions for complete doxorubicin release. The corresponding temperature profiles were mapped with 0.5 mm spatial resolution using an embedded needle thermocouple; drug release was quantified using fluorimetry. Complete release over the HIFU focal area was obtained for 6-s continuous wave exposure at 5.2 MPa peak rarefactional pressure, i.e. under exposure conditions for which the temperature exceeded 43° C throughout the focal volume. For a given HIFU energy input, both the final temperature reached and the rate of heating were found to affect release significantly. However, ThermoDox® release was achieved only due to thermal effects of HIFU, and not by other ultrasound effects, such as cavitation without heating, showing robustness of HIFU-induced hyperthermia as a release mechanism.

  16. Interaction of fluoxetine with phosphatidylcholine liposomes.

    PubMed

    Momo, Federico; Fabris, Sabrina; Stevanato, Roberto

    2005-10-22

    Fluoxetine (Prozac) is one of the latest of a new generation of antidepressants, approved by FDA in 2002. The interactions of fluoxetine with multilamellar liposomes of pure phosphatidylcholine (PC) or containing cholesterol 10% molar were studied as a function of the lipid chain lengths, using differential scanning calorimetry and spin labelling EPR techniques. The DSC profiles of the gel-to-fluid state transition of liposomes of DMPC (C14:0) are broadened and shifted towards lower temperatures at increasing dopant concentrations and, with less than 10% fluoxetine, any detectable transition is destroyed. The broadened profiles and the lowered transition temperatures demonstrate that both the size and the packing of the cooperative units undergoing the transition are modified by fluoxetine, leading to a looser and more flexible bilayer. No phase separation was observed. The effects of fluoxetine on the thermotropic phase behaviour of DPPC (C16:0) and, even more, of DSPC (C18:0) are different from that of DMPC. In fact, in the former cases, two peaks appeared at increasing dopant concentrations, suggesting the occurrence of a phase separation phenomenon, which is a sign of a binding of fluoxetine in the phosphate region. In cholesterol containing membranes, fluoxetine, even at low concentrations, leads to a general corruption of the membrane, both in terms of packing and cooperativity, and the formation of any new phase is no longer observable. EPR spectra reflect the disordered motion of acyl chains in the bilayer. It was found that fluoxetine lowers the order of the lipid chains mainly in correspondence of the fifth carbon position of SASL, indicating a possible accumulation near the interfacial region.

  17. Liposomal cisplatin: a new cisplatin formulation.

    PubMed

    Stathopoulos, George P

    2010-09-01

    Over the last three decades, cisplatin has been one of the most effective cytotoxic agents, but its administration has been hindered by its nephrotoxicity, neurotoxicity and myelo toxicity. Recently, liposomal cisplatin, lipoplatin, has been formulated and tested thoroughly in preclinical (in vitro) and phase I, II and III trials, as documented in the literature. Experiments in animals showed that lipoplatin is less toxic than cisplatin and that it produces tumour reduction. The histological examination of treated tumours from mouse xenografts was consistent with apoptosis in the tumour cells in a mechanism similar to that of cisplatin. Lipoplatin infusion in patients and measurements of platinum levels in tumour specimens showed 10-50 times higher levels in tumours and metastases than in the adjacent normal specimens. A phase I-II study using a combination of lipoplatin and gemcitabine in pretreated patients (with disease progression or stable disease) with advanced pancreatic cancer was conducted. No nephrotoxicity was observed. With lipoplatin monotherapy the dose-limiting toxicity was determined to be 350 mg/m and the maximum tolerated dose 300 mg/m; when used in combination with paclitaxel the dose-limiting toxicity for lipoplatin was 250 mg/m and for paclitaxel 175 mg/m, and the maximum tolerated dose was 200 and 175 mg/m, respectively. In two phase II randomized studies comparing the lipoplatin combination versus the cisplatin combination, it was found that the former was statistically significantly less toxic than the latter, whereas the response rate and survival were similar. Up to now, the data on lipoplatin treatment in malignant tumours are quite impressive, because of the negligible toxicity and because it is equal if not superior to cisplatin with regard to response rate. This review aims to chronologically document publications relevant to liposomal cisplatin to date.

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

    PubMed Central

    2013-01-01

    Background Despite the potential of improving the delivery of epigenetic drugs, the subsequent assessment of changes in their epigenetic activity is largely dependent on the availability of a suitable and rapid screening bioassay. Here, we describe a cell-based assay system for screening gene reactivation. Methods A cell-based assay system (EPISSAY) was designed based on a silenced triple-mutated bacterial nitroreductase TMnfsB fused with Red-Fluorescent Protein (RFP) expressed in the non-malignant human breast cell line MCF10A. EPISSAY was validated using the target gene TXNIP, which has previously been shown to respond to epigenetic drugs. The potency of a epigenetic drug model, decitabine, formulated with PEGylated liposomes was also validated using this assay system. Results Following treatment with DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors such as decitabine and vorinostat, increases in RFP expression were observed, indicating expression of RFP-TMnfsB. The EPISSAY system was then used to test the potency of decitabine, before and after PEGylated liposomal encapsulation. We observed a 50% higher potency of decitabine when encapsulated in PEGylated liposomes, which is likely to be due to its protection from rapid degradation. Conclusions The EPISSAY bioassay system provides a novel and rapid system to compare the efficiencies of existing and newly formulated drugs that reactivate gene expression. PMID:23497118

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

    PubMed

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

    2013-03-13

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

  20. The Antimicrobial Activity of Liposomal Lauric Acids Against Propionibacterium acnes

    PubMed Central

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

    2009-01-01

    This study evaluated the antimicrobial activity of lauric acid (LA) and its liposomal derivatives against Propionibacterium acnes (P. acnes), the bacterium that promotes inflammatory acne. First, the antimicrobial study of three free fatty acids (lauric acid, palmitic acid and oleic acid) demonstrated that LA gives the strongest bactericidal activity against P. acnes. However, a setback of using LA as a potential treatment for inflammatory acne is its poor water solubility. Then the LA was incorporated into a liposome formulation to aid its delivery to P. acnes. It's demonstrated that the antimicrobial activity of LA was not only well maintained in its liposomal derivatives but also enhanced at low LA concentration. In addition, the antimicrobial activity of LA-loaded liposomes (LipoLA) mainly depended on the LA loading concentration per single liposomes. Further study found that the LipoLA could fuse with the membranes of P. acnes and release the carried LA directly into the bacterial membranes, thereby killing the bacteria effectively. Since LA is a natural compound that is the main acid in coconut oil and also resides in human breast milk and liposomes have been successfully and widely applied as a drug delivery vehicle in the clinic, the LipoLA developed in this work holds great potential of becoming an innate, safe and effective therapeutic medication for acne vulgaris and other P. acnes associated diseases. PMID:19665786

  1. Development and characterization of multilamellar liposomes containing pyridostigmine.

    PubMed

    Souza, Ana Carolina Moreira; Grabe-Guimarães, Andrea; Souza, Jacqueline; Botacim, Wallace Entringer; Almeida, Tamara Marine; Frézard, Fréderic Jean Georges; Silva Barcellos, Neila Márcia

    2014-06-01

    Pyridostigmine has cardioprotective activity in both free and liposomal forms. This study aimed to develop and characterize liposomal formulations of pyridostigmine. For this, a spectrophotometric ultraviolet (UV) analytical method, at 270 nm, was developed and validated to quantify liposomal pyridostigmine. The method was linear in ranges from 0.02 to 0.09 mg/mL. The accuracy of this method was determined intra- and inter-day; the results of coefficient of variation were of 1.73-2.72% and 0.32-2.32%, respectively. The accuracy ranged between 99.45% and 101.12%. The method has not changed by influence of liposomal matrix and demonstrated being able to quantify pyridostigmine in liposomes. Two liposomal multilamellar formulations were developed: a constituted by dystearoyl-phosphatidylcholine (DSPC) and cholesterol (CHOL) other by dioleil-phosphatidylcholine (DOPC) and CHOL. The encapsulation efficiency was determined as 23.4% and 15.4%, respectively. Analyses of size and release of pyridostigmine from the formulations were made and the results showed that the formulations are viable for future studies in vivo.

  2. Molecular targeting of liposomal nanoparticles to tumor microenvironment

    PubMed Central

    Zhao, Gang; Rodriguez, B Leticia

    2013-01-01

    Liposomes are biodegradable and can be used to deliver drugs at a much higher concentration in tumor tissues than in normal tissues. Both passive and active drug delivery by liposomal nanoparticles can significantly reduce the toxic side effects of anticancer drugs and enhance the therapeutic efficacy of the drugs delivered. Active liposomal targeting to tumors is achieved by recognizing specific tumor receptors through tumor-specific ligands or antibodies coupled onto the surface of the liposomes, or by stimulus-sensitive drug carriers such as acid-triggered release or enzyme-triggered drug release. Tumors are often composed of tumor cells and nontumor cells, which include endothelial cells, pericytes, fibroblasts, stromal, mesenchymal cells, innate, and adaptive immune cells. These nontumor cells thus form the tumor microenvironment, which could be targeted and modified so that it is unfavorable for tumor cells to grow. In this review, we briefly summarized articles that had taken advantage of liposomal nanoparticles as a carrier to deliver anticancer drugs to the tumor microenvironment, and how they overcame obstacles such as nonspecific uptake, interaction with components in blood, and toxicity. Special attention is devoted to the liposomal targeting of anticancer drugs to the endothelium of tumor neovasculature, tumor associated macrophages, fibroblasts, and pericytes within the tumor microenvironment. PMID:23293520

  3. Click modification of multifunctional liposomes bearing hyperbranched polyether chains.

    PubMed

    Fritz, Thomas; Hirsch, Markus; Richter, Felix C; Müller, Sophie S; Hofmann, Anna M; Rusitzka, Kristiane A K; Markl, Jürgen; Massing, Ulrich; Frey, Holger; Helm, Mark

    2014-07-14

    Aiming at controlled modification of liposomal surface structures, we describe a postpreparational approach for surface derivatization of a new type of multifunctional, sterically stabilized liposomes. Application of dual centrifugation (DC) resulted in high encapsulation efficiencies above 50% at very small batch sizes with a total volume of 150 μL, which were conductive to fast and efficient optimization of variegated surface modification reactions. Cholesterol-polymer amphiphiles, including complex hyperbranched polyether structures bearing 1-4 terminal alkynes, were used in DC formulations to provide steric stabilization. The alkyne moieties were explored as anchors for the conjugation of small molecules to the liposomal surface via click chemistry, binding 350-450 fluorophores per liposome as examples for surface active molecules. Using Förster resonance energy transfer (FRET) spectroscopy, the conjugation reaction as well as the uptake of FRET-labeled liposomes by RBE4 cells was monitored, and the distribution of the fluorescent lipids among cellular structures and membranes could be studied. Thus, the combination of clickable hyperbranched amphiphiles and dual centrifugation provides access to well-defined liposomal formulations with a variety of surface moieties.

  4. Contact deformation of liposome in the presence of osmosis.

    PubMed

    Foo, Ji-Jinn; Chan, Vincent; Liu, Kuo-Kang

    2003-11-01

    The role of osmotic pressure on the geometry of adherent liposome remains an intricate question in the mechanics of supramolecular structures. In this study, confocal reflection interference contrast microscopy in combination with cross-polarized microscopy was applied to probe the geometry of deformed liposome on fused silica substrates through the determination of a vesicle-substrate separation profile. In parallel, a theoretical model which describes the large deformation of the lipid bilayer membrane under both out-plane bending and in-plane shear forces is developed. Then, the global deformation geometry of the adherent liposome is rigorously compared with our experimental data. It is shown that the adhesion contact area increases in dimension, the liposome volume decreases, and the vesicle height decreases under the reduced osmotic pressure. The coupling of experimental data and a modified theoretical framework of the adherent liposome provides a more explicit result in comparison with previous studies and demonstrates the possibility of modeling the change of liposome mechanics under the influence of osmosis.

  5. Elastic Liposomes for Topical and Transdermal Drug Delivery.

    PubMed

    Benson, Heather A E

    2017-01-01

    Elastic liposomes have been developed and evaluated as novel topical and transdermal delivery systems. They share some similarities to conventional liposomes but their composition is designed to confer flexibility and elasticity in the lipid bilayer structure. Elastic liposomes are applied non-occluded to the skin and are reported to permeate through the stratum corneum lipid lamellar regions as a result of the hydration or osmotic force in the skin. They have been investigated as drug carriers for a range of small molecules, peptides, proteins, and vaccines, both in vitro and in vivo. Following topical application, structural changes in the stratum corneum have been identified and intact elastic liposomes visualized within the stratum corneum lipid lamellar regions, but evidence of intact liposomes in the deeper viable tissues is limited. The method by which they transport their drug payload into and through the skin has been investigated but remains an area of contention. This chapter provides an overview of the development, characterization, and evaluation of elastic liposomes for delivery into and via the skin.

  6. Technological and Theoretical Aspects for Testing Electroporation on Liposomes

    PubMed Central

    Denzi, Agnese; della Valle, Elena; Esposito, Gianluca; Mir, Lluis M.; Apollonio, Francesca

    2017-01-01

    Recently, the use of nanometer liposomes as nanocarriers in drug delivery systems mediated by nanoelectroporation has been proposed. This technique takes advantage of the possibility of simultaneously electroporating liposomes and cell membrane with 10-nanosecond pulsed electric fields (nsPEF) facilitating the release of the drug from the liposomes and at the same time its uptake by the cells. In this paper the design and characterization of a 10 nsPEF exposure system is presented, for liposomes electroporation purposes. The design and the characterization of the applicator have been carried out choosing an electroporation cuvette with 1 mm gap between the electrodes. The structure efficiency has been evaluated at different experimental conditions by changing the solution conductivity from 0.25 to 1.6 S/m. With the aim to analyze the influence of device performances on the liposomes electroporation, microdosimetric simulations have been performed considering liposomes of 200 and 400 nm of dimension with different inner and outer conductivity (from 0.05 to 1.6 S/m) in order to identify the voltage needed for their poration. PMID:28393078

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

    PubMed

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

    2006-04-12

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

  8. Liposomal delivery system for topical anaesthesia of the palatal mucosa.

    PubMed

    Franz-Montan, M; de Paula, E; Groppo, F C; Silva, A L R; Ranali, J; Volpato, M C

    2012-01-01

    An effective topical agent to reduce pain during local anaesthesia of the palate is not yet available. The aim of the present study was to evaluate the efficiency of liposome-encapsulated ropivacaine in different concentrations for topical anaesthesia of the palatal mucosa. In this single-blinded, placebo-controlled, crossover study 40 (20 male) healthy volunteers were randomised to be given: liposome-encapsulated 2% ropivacaine, liposome-encapsulated 1% ropivacaine, a eutectic mixture of 2.5% lidocaine and 2.5% prilocaine (EMLA), and liposomal placebo gel, topically on to the palatal mucosa of the right canine region for 5 min each, at four different sessions. Pain associated with insertion of a 30G needle, and with injection of a local anaesthetic, was rated on a visual analogue scale (VAS). The effect of liposomal ropivacaine 1% and 2% did not differ from that of placebo (p=0.3 and p=0.1, respectively) in reducing pain during insertion of the needle. Lower VAS were obtained with EMLA. In this group VAS were lower in women than men (p=0.007). There was no difference in VAS among groups (p=0.3) as far as injection of the local anaesthetic was concerned. In conclusion, liposomal-encapsulated ropivacaine formulations did not reduce the pain of insertion of a needle into the palatal mucosa. None of the anaesthetic formulations tested, including the positive control (EMLA), were effective in reducing the pain of an injection of local anaesthetic compared with placebo.

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

    PubMed

    Iorio, Richard

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

  10. [Trends in the development of research in the field of liposomes (review of patent literature)].

    PubMed

    Nesytova, N Iu; Paleva, N S; Il'ina, E V; Shenk, P; Bendas, F; Nun, P

    1990-01-01

    The review embraces major trends and tendencies in liposome studies and is based on the statistical and qualitative analysis of patent information issued in the period 1970-1988. Special attention is devoted to the analysis of patents in liposome production techniques, their lipid composition, and application in pharmaceutical and cosmetic industries and also for the diagnostic and therapeutic purposes. Liposomal preparations are shown to be superior to common drugs as concerns, in particular, liposomes containing medicinal agents for prolonged use (including hormones, antibiotics, cytostatics, and immunostimulants) and liposomes used in dermatological practice. Liposome-based assessment of application prospects is given.

  11. Combinatorial Library Screening with Liposomes for Discovery of Membrane Active Peptides.

    PubMed

    Carney, Randy P; Thillier, Yann; Kiss, Zsofia; Sahabi, Amir; Heleno Campos, Jean Carlos; Knudson, Alisha; Liu, Ruiwu; Olivos, David; Saunders, Mary; Tian, Lin; Lam, Kit S

    2017-04-05

    Membrane active peptides (MAPs) represent a class of short biomolecules that have shown great promise in facilitating intracellular delivery without disrupting cellular plasma membranes. Yet their clinical application has been stalled by numerous factors: off-target delivery, a requirement for high local concentration near cells of interest, degradation en route to the target site, and, in the case of cell-penetrating peptides, eventual entrapment in endolysosomal compartments. The current method of deriving MAPs from naturally occurring proteins has restricted the discovery of new peptides that may overcome these limitations. Here we describe a new branch of assays featuring high-throughput functional screening capable of discovering new peptides with tailored cell uptake and endosomal escape capabilities. The one-bead-one-compound (OBOC) combinatorial method is used to screen libraries containing millions of potential MAPs for binding to synthetic liposomes, which can be adapted to mimic various aspects of limiting membranes. By incorporating unnatural and D-amino acids in the library, in addition to varying buffer conditions and liposome compositions, we have identified several new highly potent MAPs that improve on current standards and introduce motifs that were previously unknown or considered unsuitable. Since small variations in pH and lipid composition can be controlled during screening, peptides discovered using this methodology could aid researchers building drug delivery platforms with unique requirements, such as targeted intracellular localization.

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

    PubMed

    Ko, Young Tag; Bickel, Ulrich

    2012-06-01

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

  13. Modulation of oxidative stability of haemoglobin inside liposome-encapsulated haemoglobin

    PubMed Central

    Awasthi, Vibhudutta; Yadav, Vivek R; Goins, Beth; Phillips, William T

    2013-01-01

    The major hurdle in the formulation of liposome-encapsulated haemoglobin (LEH) is the oxidation of haemoglobin (Hb) into methaemoglobin during storage and after administration. In order to reduce this oxidative degradation, we tested various reducing conditions in the presence of catalase. We found that at 37°C more than 50% of Hb oxidized to methaemoglobin within 24 h, whereas in presence of catalase, the oxidation was significantly reduced. The effect of catalase was further enhanced by a reduction mixture containing β-NAD, d-glucose, adenine, inosine, MgCl2, KCl, KH2PO4 and Na2HPO4−, only 14% methaemoglobin was generated in the presence of catalase and reduction mixture (CRM). Contrary to the expectation, glutathione, deferoxamine and homocysteine enhanced Hb oxidation. The presence of CRM inside liposomes (250 nm) significantly decreased Hb oxidation. The results suggest that catalase and a well-defined mixture of co-factors may help control Hb oxidation for improvement in the functional life of LEH. PMID:23231644

  14. Metabolism and excretion of novel pulmonary-targeting docetaxel liposome in rabbits

    PubMed Central

    Wang, Jie; Zhang, Li; Wang, Lijuan; Liu, Zhonghong

    2017-01-01

    Our study aims to determine the metabolism and excretion of novel pulmonary-targeting docetaxel liposome (DTX-LP) using the in vitro and in vivo animal experimental models. The metabolism and excretion of DTX-LP and intravenous DTX (DTX-IN) in New Zealand rabbits were determined with ultraperformance liquid chromatography tandem mass spectrometry. We found DTX-LP and DTX-IN were similarly degraded in vitro by liver homogenates and microsomes, but not metabolized by lung homogenates. Ultra-performance liquid chromatography tandem mass spectrometry identified two shared DTX metabolites. The unconfirmed metabolite Mun differed structurally from all DTX metabolites identified to date. DTX-LP likewise had a similar in vivo metabolism to DTX-IN. Conversely, DTX-LP showed significantly diminished excretion in rabbit feces or urine, approximately halving the cumulative excretion rates compared to DTX-IN. Liposomal delivery of DTX did not alter the in vitro or in vivo drug metabolism. Delayed excretion of pulmonary-targeting DTX-LP may greatly enhance the therapeutic efficacy and reduce the systemic toxicity in the chemotherapy of non-small cell lung cancer. The identification of Mun may further suggest an alternative species-specific metabolic pathway. PMID:28066140

  15. Intraperitoneal (188)Re-Liposome delivery switches ovarian cancer metabolism from glycolysis to oxidative phosphorylation and effectively controls ovarian tumour growth in mice.

    PubMed

    Shen, Yao An; Lan, Keng Li; Chang, Chih Hsien; Lin, Liang Ting; He, Chun Lin; Chen, Po Hung; Lee, Te Wei; Lee, Yi Jang; Chuang, Chi Mu

    2016-05-01

    Cancer stem cells exhibit distinctive cellular metabolism compared with the more differentiated counterparts or normal cells. We aimed to investigate the impact of a novel radionuclide anti-cancer agent (188)Re-Liposome on stemness markers' expression and cellular metabolism in an ovarian cancer model. A 2×2 factorial experiment was designed in which factor 1 represented the drug treatment comparing (188)Re-BMEDA, a free form of (188)Re, with (188)Re-Liposome, a nanoparticle-encapsulated form of (188)Re. Factor 2 represented the delivery route, comparing intravenous with intraperitoneal delivery. Intraperitoneal delivery of (188)Re-Liposome predominantly killed the CSCs-like cells in tumours and switched metabolism from glycolysis to oxidative phosphorylation. Further, intraperitoneal delivery of (188)Re-Liposome treatment was able to block epithelial-to-mesenchymal transition (EMT) and reactivate p53 function. Collectively, these molecular changes led to a striking tumour-killing effect. Radionuclides encapsulated in liposomes may represent a novel treatment for ovarian cancer when delivered intraperitoneally (a type of loco-regional delivery). In the future, this concept may be further extended for the treatment of several relevant cancers that have been proved to be suitable for loco-regional delivery of therapeutic agents, such as colon cancer, gastric cancer, and pancreatic cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Tablets of pre-liposomes govern in situ formation of liposomes: concept and potential of the novel drug delivery system.

    PubMed

    Vanić, Željka; Planinšek, Odon; Škalko-Basnet, Nataša; Tho, Ingunn

    2014-10-01

    The purpose of this study was to develop a novel drug delivery system for challenging drugs with potential for scale-up manufacturing and controlled release of incorporated drug. Pre-liposomes powder containing metronidazole, lecithin and mannitol, prepared by spray-drying, was mixed with different tableting excipients (microcrystalline cellulose, lactose monohydrate, mannitol, dibasic calcium phosphate, pregelatinized starch, pectin or chitosan) and compressed into tablets. The delivery system was characterized with respect to (i) dry powder characteristics, (ii) mechanical tablet properties and drug release, and (iii) liposomal characteristics. The pre-liposomes powder was free-flowing, and tablets of similarly high qualities as tablets made of physical mixtures were prepared with all excipients. Liposomes were formed in situ upon tablet disintegration, dissolution or erosion depending on the type of tablet excipient used. The liposomal characteristics and drug release were found to depend on the tablet excipient. The new delivery system offers a unique synergy between the ability of liposomes to encapsulate and protect drugs and increased stability provided by compressed formulations. It can be adjusted for drug administration via various routes, e.g. oral, buccal and vaginal.

  17. Silica-based monolithic capillary columns modified by liposomes for characterization of analyte-liposome interactions by capillary liquid chromatography.

    PubMed

    Moravcová, Dana; Planeta, Josef; Wiedmer, Susanne K

    2013-11-22

    This study introduces a silica-based monolith in a capillary format (0.1 mm × 100 mm) as a support for immobilization of liposomes and its characterization in immobilized liposome chromatography. Silica-based monolithic capillary columns prepared by acidic hydrolysis of tetramethoxysilane in the presence of polyethylene glycol and urea were modified by (3-aminopropyl)trimethoxysilane, whereby amino groups were introduced to the monolithic surface. These groups undergo reaction with glutaraldehyde to form an iminoaldehyde, allowing covalent binding of pre-formed liposomes containing primary amino groups. Two types of phospholipid vesicles were used for column modification; these were 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphatidyl choline with and without 1,2-diacyl-sn-glycero-3-phospho-L-serine. The prepared columns were evaluated under isocratic separation conditions employing 20mM phosphate buffer at pH 7.4 as a mobile phase and a set of unrelated drugs as model analytes. The liposome layer on the synthesized columns significantly changed the column selectivity compared to the aminopropylsilylated monolithic stationary phase. Monolithic columns modified by liposomes were stable under the separation conditions, which proved the applicability of the suggested preparation procedure for the synthesis of capillary columns dedicated to study analyte-liposome interactions. The column efficiency originating from the silica monolith was preserved and reached, e.g., more than 120,000 theoretical plates/m for caffeine as a solute.

  18. Terpene-loaded Liposomes and Isopropyl Myristate as Chemical Permeation Enhancers Toward Liposomal Gene Delivery in Lung Cancer cells; A Comparative Study

    PubMed Central

    Saffari, Mostafa; Hoseini Shirazi, Farshad; Moghimi, Hamid Reza

    2016-01-01

    Gene therapy is in its development stage as a novel method for cancer treatment. Liposomes look promising as gene delivery vectors; however, investigations have shown that these vesicles are not doing well in some cases. It was decided here to investigate the possibility of augmentation of liposomal gene delivery by chemical penetration enhancers. Cationic liposome containing antisense oligonucleotide (AsODN) against lung cancer was prepared by ethanol injection method. Liposomal cineole and limonene (as enhancers) were prepared by film hydration method. Isopropyl myristate (IPM) was also investigated as penetration enhancer. Liposomes were evaluated for their size, zeta potential and encapsulation efficiency. Cancer cells (A549) were pretreated with liposomal terpenes prior to treatment with liposomal antisense or scrambled oligonucleotide. Cell viability was evaluated by MTT assay. Oligonucleotide -containing liposome showed particle size of about115 nm and zeta potential of 0.6 mV. Liposomal cineole significantly (P<0.05) increased specific activity of liposomal antisense but limonene didn’t show such an effect. IPM increased both specific and non-specific cytotoxicity of Oligonucleotide. These results show that penetration enhancers (such as cineole) may be used for improving liposomal gene delivery and to reduce non-specific toxicity. Concentration and chemical nature of enhancer has prominent effect in their efficacy. PMID:27980561

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

    PubMed

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

    2016-01-01

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

  20. The Combined Effect of Encapsulating Curcumin and C6 Ceramide in Liposomal Nanoparticles against Osteosarcoma

    PubMed Central

    Dhule, Santosh S; Penfornis, Patrice; He, Jibao; Harris, Michael R; Terry, Treniece; John, Vijay; Pochampally, Radhika

    2014-01-01

    This study examines the anti-tumor potential of curcumin and C6 ceramide (C6) against osteosarcoma (OS) cell lines when both are encapsulated in the bilayer of liposomal nanoparticles. Three liposomal formulations were prepared – curcumin liposomes, C6 liposomes and C6-curcumin liposomes. Curcumin in combination with C6 showed 1.5 times enhanced cytotoxic effect in the case of MG-63 and KHOS OS cell lines, in comparison with curcumin liposomes alone. Importantly, C6-curcumin liposomes were found to be less toxic on untransformed human cells (human mesenchymal stem cells) in comparison to OS cell lines. In addition, cell cycle assays on a KHOS cell line after treatment revealed that curcumin only liposomes induced G2/M arrest by upregulation of cyclin B1, while C6 only liposomes induced G1 arrest by downregulation of cyclin D1. C6-curcumin liposomes induced G2/M arrest and showed a combined effect in the expression levels of cyclin D1 and cyclin B1. The efficiency of the preparations was tested in vivo using a human osteosarcoma xenograft assays. Using pegylated liposomes to increase the plasma half-life and tagging with folate (FA) for targeted delivery in vivo, a significant reduction in tumor size was observed with C6-curcumin-FA liposomes. The encapsulation of two water insoluble drugs, curcumin and C6, in the lipid bilayer of liposomes enhances the cytotoxic effect and validates the potential of combined drug therapy. PMID:24380633

  1. Liposome chaperon in cell-free membrane protein synthesis: one-step preparation of KcsA-integrated liposomes and electrophysiological analysis by the planar bilayer method.

    PubMed

    Ando, M; Akiyama, M; Okuno, D; Hirano, M; Ide, T; Sawada, S; Sasaki, Y; Akiyoshi, K

    2016-02-01

    Chaperoning functions of liposomes were investigated using cell-free membrane protein synthesis. KcsA potassium channel-reconstituted liposomes were prepared directly using cell-free protein synthesis. In the absence of liposomes, all synthesized KcsA protein aggregated. In the presence of liposomes, however, synthesized KcsA spontaneously integrated into the liposome membrane. The KscA-reconstituted liposomes were transferred to the planar bilayer across a small hole in a thin plastic sheet and the channel function of KcsA was examined. The original electrophysiological activities, such as voltage- and pH-dependence, were observed. These results suggested that in cell-free membrane protein synthesis, liposomes act as chaperones, preventing aggregation and assisting in folding and tetrameric formation, thereby allowing full channel activity.

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

    PubMed

    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

  3. cDNA cloning and expression of Contractin A, a phospholipase A2-like protein from the globiferous pedicellariae of the venomous sea urchin Toxopneustes pileolus.

    PubMed

    Hatakeyama, Tomomitsu; Higashi, Erika; Nakagawa, Hideyuki

    2015-12-15

    Venomous sea urchins contain various biologically active proteins that are toxic to predators. Contractin A is one such protein contained within the globiferous pedicellariae of the venomous sea urchin Toxopneustes pileolus. This protein exhibits several biological activities, such as smooth muscle contraction and mitogenic activity. N-terminal amino acid residues of Contractin A have been determined up to 37 residues from the purified protein. In this study, we cloned cDNA for Contractin A by reverse transcription-PCR using degenerate primers designed on the basis of its N-terminal amino acid sequence. Analysis of the cDNA sequence indicated that Contractin A is composed of 166 amino acid residues including 31 residues of a putative signal sequence, and has homology to the sequence of phospholipase A2 from various organisms. In this study, recombinant Contractin A was expressed in Escherichia coli cells, and the protein was subjected to an assay to determine lipid-degrading activity using carboxyfluorescein-containing liposomes. As a result, Contractin A was found to exhibit Ca(2+)-dependent release of carboxyfluorescein from the liposomes, suggesting that Contractin A has phospholipase A2 activity, which may be closely associated with its biological activities.

  4. Marine lipid-based liposomes increase in vivo FA bioavailability.

    PubMed

    Cansell, Maud; Nacka, Fabienne; Combe, Nicole

    2003-05-01

    Liposomes made from an extract of natural marine lipids and containing a high n-3 PUFA lipid ratio were envisaged as oral route vectors for FA supplements in order to increase PUFA bioavailability. The absorption of FA in thoracic lymph duct-cannulated rats, after intragastric feeding of dietary fats in the form of liposomes or fish oil, was compared. Lipid and FA analyses were also performed on feces. Five mole percent alpha-tocopherol was added to fish oil and incorporated into the liposome membrane. The influence of alpha-tocopherol on FA lymph recovery was also investigated. In vivo, FA absorption in rats was favored by liposomes (98 +/- 1%) compared to fish oil (73 +/- 6%). In the same way, the DHA proportion in lymph was higher after liposome ingestion (78%) than after fish oil ingestion (47%). However, phospholipid (PL) concentration in lymph was not affected by the kind of dietary fat ingested, suggesting a PL regulation due to de novo TAG synthesis. The influence of the intramolecular distribution of n-3 PUFA in dietary lipids (TAG and PL) on the intramolecular FA distribution in TAG of chylomicrons was also investigated. The results obtained showed that the distribution of n-3 PUFA esterified on the sn-2 position of chylomicron TAG depended on the lipid source administered. All these results correlated, at least partly, with in vitro liposome behavior under conditions that mimic those of the gastrointestinal tract. As a whole, this study pointed out that marine PL may constitute an attractive material for the development of liposomes as oral PUFA supplements.

  5. Liposomal formulations of amphotericin B: differences according to the scientific evidence.

    PubMed

    Azanza, José Ramón; Sádada, Belén; Reis, Joana

    2015-12-01

    This article presents an overview of the characteristics of liposomes as drug carriers, particularly in relation to liposomal formulations of amphotericin B. General features regarding structure, liposome-cell interactions, stability, encapsulation of active substances and elimination of liposomes are described. Up to the present time extensive efforts to produce similar or bioequivalent products of amphotericin B formulations, in particular in the case of liposomal amphotericin B, have been unsuccessful in spite of having a very similar composition and even an apparently identical manufacturing process. Guidelines for the development of generic liposomal formulations developed by the FDA and EMA are also summarized. Based on the available evidence of the composition of liposomes, any differences in the manufacturing process even if the same lipid composition is used may result in different final products. Therefore, it seems unreasonable to infer that all amphotericin B liposomal formulations are equal in efficacy and safety.

  6. Clinical development of liposome-based drugs: formulation, characterization, and therapeutic efficacy

    PubMed Central

    Chang, Hsin-I; Yeh, Ming-Kung

    2012-01-01

    Research on liposome formulations has progressed from that on conventional vesicles to new generation liposomes, such as cationic liposomes, temperature sensitive liposomes, and virosomes, by modulating the formulation techniques and lipid composition. Many research papers focus on the correlation of blood circulation time and drug accumulation in target tissues with physicochemical properties of liposomal formulations, including particle size, membrane lamellarity, surface charge, permeability, encapsulation volume, shelf time, and release rate. This review is mainly to compare the therapeutic effect of current clinically approved liposome-based drugs with free drugs, and to also determine the clinical effect via liposomal variations in lipid composition. Furthermore, the major preclinical and clinical data related to the principal liposomal formulations are also summarized. PMID:22275822

  7. Behaviour of liposomes loaded with bovine serum albumin during in vitro digestion.

    PubMed

    Liu, Weilin; Ye, Aiqian; Liu, Wei; Liu, Chengmei; Han, Jianzhong; Singh, Harjinder

    2015-05-15

    This study examined the stability of liposomes loaded with negatively charged protein (bovine serum albumin, BSA) during in vitro digestion. Zeta-potential and morphology measurements confirmed that BSA-loaded liposomes were successfully prepared, with an encapsulation efficiency of around 34%. The encapsulated BSA and the integrity of the liposomes remained unchanged with time when the liposomes were digested in a simulated gastric environment, suggesting that the liposomal membrane protected the entrapped BSA from pepsin hydrolysis. BSA-loaded liposomes exhibited lower stability in simulated intestinal fluid, as shown by damaged membranes and the release of free fatty acids. Also, lipolysis kinetics revealed that bile salts and ionic strength could facilitate a high level of free fatty acid release. This work further supplemented our knowledge about the effects of gastrointestinal digestion conditions on liposomal properties and provided valuable information for the design of liposome formulations for the food and health care industries.

  8. Enhanced combination therapy effect on paclitaxel-resistant carcinoma by chloroquine co-delivery via liposomes

    PubMed Central

    Gao, Menghua; Xu, Yuzhen; Qiu, Liyan

    2015-01-01

    A novel composite liposomal system co-encapsulating paclitaxel (PTX) with chloroquine phosphate (CQ) was designed for treating PTX-resistant carcinoma. It was confirmed that liposomal CQ can sensitize PTX by means of autophagy inhibition and competitively binding with multidrug-resistance transporters. Furthermore, according to the in vitro cytotoxicity and apoptosis assay, real-time observation of cellular uptake, and in vivo tissue distribution study, co-encapsulation of PTX and CQ in liposomes was validated as superior to the mixture of PTX liposome plus CQ liposome due to the simultaneous delivery and synergetic effect of the two drugs. Consequently, this composite liposome achieved significantly stronger anticancer efficacy in vivo than the PTX liposome plus CQ liposome mixture. This study helps to guide and enlighten ongoing and future clinical trials about the optimal administration modes for drug combination therapy. PMID:26543365

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

    PubMed

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

    2015-01-01

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

  10. Preparation and evaluation of cyclodextrin polypseudorotaxane with PEGylated liposome as a sustained release drug carrier

    PubMed Central

    Hayashida, Kayoko; Higashi, Taishi; Kono, Daichi; Motoyama, Keiichi; Wada, Koki

    2014-01-01

    Summary Cyclodextrins (CDs) can form polypseudorotaxanes (PPRXs) with drugs or drug carriers possessing linear polymers such as polyethylene glycol (PEG). On the other hand, PEGylated liposomes have been utilized as a representative anticancer drug carrier. However, little is known about the formation of CD PPRX with PEGylated liposome. In the present study, we first report the formation of CD PPRX with PEGylated liposome and evaluate it as a sustained release drug carrier. PEGylated liposome encapsulating doxorubicin was disrupted by the addition of α-CD. Meanwhile, γ-CD included two PEG chains and/or one bending PEG chain of PEGylated liposome and formed PPRX without the disruption of the membrane integrity of the PEGylated liposome. Moreover, the release of doxorubicin and/or PEGylated liposome encapsulating doxorubicin from the PPRX was prolonged in accordance with the matrix type release mechanism. These findings suggest the potential of γ-CD PPRX as sustained release carriers for PEGylated liposome products. PMID:25550741

  11. Preparation and evaluation of cyclodextrin polypseudorotaxane with PEGylated liposome as a sustained release drug carrier.

    PubMed

    Hayashida, Kayoko; Higashi, Taishi; Kono, Daichi; Motoyama, Keiichi; Wada, Koki; Arima, Hidetoshi

    2014-01-01

    Cyclodextrins (CDs) can form polypseudorotaxanes (PPRXs) with drugs or drug carriers possessing linear polymers such as polyethylene glycol (PEG). On the other hand, PEGylated liposomes have been utilized as a representative anticancer drug carrier. However, little is known about the formation of CD PPRX with PEGylated liposome. In the present study, we first report the formation of CD PPRX with PEGylated liposome and evaluate it as a sustained release drug carrier. PEGylated liposome encapsulating doxorubicin was disrupted by the addition of α-CD. Meanwhile, γ-CD included two PEG chains and/or one bending PEG chain of PEGylated liposome and formed PPRX without the disruption of the membrane integrity of the PEGylated liposome. Moreover, the release of doxorubicin and/or PEGylated liposome encapsulating doxorubicin from the PPRX was prolonged in accordance with the matrix type release mechanism. These findings suggest the potential of γ-CD PPRX as sustained release carriers for PEGylated liposome products.

  12. [The potentials for immunization against influenza using liposome-incorporated viral surface antigens].

    PubMed

    Burducea, O; Marcheş, F; Duţu, C; Grancea, C; Nicolau, A; Păun, C

    1989-01-01

    Studies were conducted using uni- and multilamellar liposomes to establish optimum conditions for influenza antigen incorporation in view of their transport to the target cells for experimental influenza prophylaxis in hybrid white mice. Radiometric determinations showed a good level of preparation purification, a good efficiency of incorporation in liposomes of the active biological material, the liposome linked radioactivity distribution among different organs. Charged liposomes induced solid and long lasting resistance against influenza control infection.

  13. Temporal Control of Membrane Fusion through Photolabile PEGylation of Liposome Membranes.

    PubMed

    Kong, Li; Askes, Sven H C; Bonnet, Sylvestre; Kros, Alexander; Campbell, Frederick

    2016-01-22

    Membrane fusion results in the transport and mixing of (bio)molecules across otherwise impermeable barriers. In this communication, we describe the temporal control of targeted liposome-liposome membrane fusion and contents mixing using light as an external trigger. Our method relies on steric shielding and rapid, photoinduced deshielding of complementary fusogenic peptides tethered to opposing liposomal membranes. In an analogous approach, we were also able to demonstrate precise spatiotemporal control of liposome accumulation at cellular membranes in vitro.

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

    PubMed

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

    2016-03-01

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

  15. Development and characterization of polymer-coated liposomes for vaginal delivery of sildenafil citrate.

    PubMed

    Refai, Hanan; Hassan, Doaa; Abdelmonem, Rehab

    2017-11-01

    Vaginal administration of sildenafil citrate has shown recently to develop efficiently the uterine lining with subsequent successful embryo implantation following in vitro fertilization. The aim of the present study was to develop sildenafil-loaded liposomes coated with bioadhesive polymers for enhanced vaginal retention and improved drug permeation. Three liposomal formulae were prepared by thin-film method using different phospholipid:cholesterol ratios. The optimal liposomal formulation was coated with bioadhesive polymers (chitosan and HPMC). A marked increase in liposomal size and zeta potential was observed for all coated liposomal formulations. HPMC-coated liposomes showed the greater bioadhesion and higher entrapment efficiency than chitosan-coated formulae. The in vitro release studies showed prolonged release of sildenafil from coated liposomes as compared to uncoated liposomes and sildenafil solution. Ex vivo permeation study revealed the enhanced permeation of coated relative to uncoated liposomes. Chitosan-coated formula demonstrated highest drug permeation and was thus selected for further investigations. Transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR) confirmed the successful coating of the liposomes by chitosan. Histopathological in vivo testing proved the efficacy of chitosan-coated liposomes to improve blood flow to the vaginal endometrium and to increase endometrial thickness. Chitosan-coated liposomes can be considered as potential novel drug delivery system intended for the vaginal administration of sildenafil, which would prolong system's retention at the vaginal site and enhance the permeation of sildenafil to uterine blood circulation.

  16. Safety of novel liposomal drugs for cancer treatment: Advances and prospects.

    PubMed

    He, Keyu; Tang, Meng

    2017-09-15

    Liposome is a kind of prospective abiotic drug delivery system for cancer treatment. Novel liposomes modified with PEG, cationic lipids and highly selective molecules achieve better stability, half-life and selectivity as well as less severe side effects. However, novel liposomes are still not nontoxic. PEG on the surface of liposomes interfere the combination of cancer cells and drugs. Cationic liposomes can induce oxidative damage and cytotoxicity to normal tissues. To further improve the safety of liposomal drugs, liposomal drugs must be highly selective to cancer tissues and cancer cells, at the same time, induce minimum damage to normal cells. It is necessary to gather several advantages of novel liposomes. The ideal targeted drug delivery system is like a multistage rocket. Firstly, the liposomal drugs should be sensitive to the specific environment of cancer tissues and accumulate in there. Secondly, the liposomes could selectively combine with cancer cells by surface modification. Lastly, in cancer cells, drugs release from the carriers rapidly. What's more, form the records of clinical researches, the side effects induced by liposomal drugs, such as acute infusion reaction and hand-foot syndrome(HFS), are also unignorable. More attention should be paid to these safety problems in new liposomal drugs research and development. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    PubMed

    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.

  18. Improved permeability of acyclovir: optimization of mucoadhesive liposomes using the phospholipid vesicle-based permeation assay.

    PubMed

    Naderkhani, Elenaz; Erber, Astrid; Škalko-Basnet, Nataša; Flaten, Gøril Eide

    2014-02-01

    The antiviral drug acyclovir (ACV) suffers from poor solubility both in lipophilic and hydrophilic environment, leading to low and highly variable bioavailability. To overcome these limitations, this study aimed at designing mucoadhesive ACV-containing liposomes to improve its permeability. Liposomes were prepared from egg phosphatidylcholine (E-PC) and E-PC/egg phosphatidylglycerol (E-PC/E-PG) and their surfaces coated with Carbopol. All liposomal formulations were fully characterized and for the first time the phospholipid vesicle-based permeation assay (PVPA) was used for testing in vitro permeability of drug from mucoadhesive liposome formulations. The negatively charged E-PC/E-PG liposomes could encapsulate more ACV than neutral E-PC liposomes. Coating with Carbopol increased the entrapment in the neutral E-PC liposomes. The incorporation of ACV into liposomes exhibited significant increase in its in vitro permeability, compared with its aqueous solution. The neutral E-PC liposomal formulations exhibited higher ACV permeability values compared with charged E-PC/E-PG formulations. Coating with Carbopol significantly enhanced the permeability from the E-PC/E-PG liposomes, as well as sonicated E-PC liposomes, which showed the highest permeability of all tested formulations. The increased permeability was according to the formulations' mucoadhesive properties. This indicates that the PVPA is suitable to distinguish between permeability of ACV from different mucoadhesive liposome formulations developed for various routes of administration.

  19. Nebulization of ultradeformable liposomes: the influence of aerosolization mechanism and formulation excipients.

    PubMed

    Elhissi, Abdelbary M A; Giebultowicz, Joanna; Stec, Anna A; Wroczynski, Piotr; Ahmed, Waqar; Alhnan, Mohamed Albed; Phoenix, David; Taylor, Kevin M G

    2012-10-15

    Ultradeformable liposomes are stress-responsive phospholipid vesicles that have been investigated extensively in transdermal delivery. In this study, the suitability of ultradeformable liposomes for pulmonary delivery was investigated. Aerosols of ultradeformable liposomes were generated using air-jet, ultrasonic or vibrating-mesh nebulizers and their stability during aerosol generation was evaluated using salbutamol sulphate as a model hydrophilic drug. Although delivery of ultradeformable liposome aerosols in high fine particle fraction was achievable, the vesicles were very unstable to nebulization so that up to 98% drug losses were demonstrated. Conventional liposomes were relatively less unstable to nebulization. Moreover, ultradeformable liposomes tended to aggregate during nebulization whilst conventional vesicles demonstrated a "size fractionation" behaviour, with smaller liposomes delivered to the lower stage of the impinger and larger vesicles to the upper stage. A release study conducted for 2 h showed that ultradeformable liposomes retained only 30% of the originally entrapped drug, which was increased to 53% by inclusion of cholesterol within the formulations. By contrast, conventional liposomes retained 60-70% of the originally entrapped drug. The differences between ultradeformable liposomes and liposomes were attributed to the presence of ethanol or Tween 80 within the elastic vesicle formulations. Overall, this study demonstrated, contrary to our expectation, that materials included with the aim of making the liposomes more elastic and ultradeformable to enhance delivery from nebulizers were in fact responsible for vesicle instability during nebulization and high leakage rates of the drug. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    PubMed

    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.

  1. Effect of formulation design and freeze-drying on properties of fluconazole multilamellar liposomes

    PubMed Central

    El-Nesr, Ola H.; Yahiya, Soad A.; El-Gazayerly, Omaima N.

    2010-01-01

    Fluconazole-entrapped multilamellar liposomes were prepared using the thin-film hydration method. The effects of cholesterol molar ratio, charge-inducing agents, and α-tocopherol acetate on encapsulation efficiency values and in vitro drug release of multilamellar liposomes were studied. Freeze-dried liposomal products were prepared with or without cryoprotectants. Results showed that incorporation of stearylamine resulted in an increased entrapment of fluconazole, whereas incorporation of dicetyl phosphate decreased the drug entrapment efficiency. The incorporation of α-tocopherol acetate into fluconazole multilamellar liposomes resulted in the increase of entrapment efficiency of fluconazole liposomes. In vitro release studies revealed that incorporation of cholesterol into multilamellar liposomal formulations decreased drug permeability from formulations. Positively charged fluconazole multilamellar liposomes gave rise to a slow release rate compared to neutral liposomes whereas negatively charged fluconazole liposomes showed a rapid release rate. Physical stability studies showed that lyophilized cake of liposomes without cryoprotectants was compact and difficult to reconstitute compared to fluffy easily reconstituted cakes upon using cryoprotectants. Fluconazole retained in freeze-dried liposomes without cryoprotectants was 63.452% compared to 91.877% using three grams of trehalose as a cryoprotectant per gram lipid in positively charged multilamellar liposomes. Physical stability studies showed superior potentials of the lyophilized product after reconstitution in comparison with those of a solution product. PMID:23960730

  2. In vitro spectroscopic study of piperine-encapsulated nanosize liposomes.

    PubMed

    Pentak, Danuta

    2016-03-01

    Black pepper is a source of effective antioxidants. It contains several powerful antioxidants and is thus one of the most important spices for preventing and curtailing oxidative stress. There is considerable interest in the development of a drug-delivery systems that would result in the selective delivery of antioxidants to tissues in sufficient concentrations to ameliorate oxidant-induced tissue injuries. Liposomes are biocompatible, biodegradable and nontoxic artificial phospholipid vesicles that offer the possibility of carrying hydrophilic, hydrophobic and amphiphilic molecules. This article focuses on the use of liposomes for the delivery of antioxidants in the prevention or treatment of pathological conditions related to oxidative stress. Liposome formulations of piperine were analyzed with various spectroscopic methods. The formulation with the highest entrapment efficiency (90.5%) was formulated with an L-α-phosphatidylcholine dipalmitoyl (DPPC):piperine, 30:1 molar ratio, and total lipid count of 19.47 mg/ml in the final liposomal preparation. The liposome formulation was found to be stable after storage at 4 °C, protected from light, for a minimum of 3 weeks. The incremental process of piperine penetration through the phospholipid membrane was analyzed using the FT-IR, UV-Vis and NMR methods. Temperature stability studies carried out at 37 °C showed the highest percentage of piperine release in the first 3 h of incubation.

  3. An efficient liposome based method for antioxidants encapsulation.

    PubMed

    Paini, Marco; Daly, Sean Ryan; Aliakbarian, Bahar; Fathi, Ali; Tehrany, Elmira Arab; Perego, Patrizia; Dehghani, Fariba; Valtchev, Peter

    2015-12-01

    Apigenin is an antioxidant that has shown a preventive activity against different cancer and cardiovascular disorders. In this study, we encapsulate apigenin with liposome to tackle the issue of its poor bioavailability and low stability. Apigenin loaded liposomes are fabricated with food-grade rapeseed lecithin in an aqueous medium in absence of any organic solvent. The liposome particle characteristics, such as particle size and polydispersity are optimised by tuning ultrasonic processing parameters. In addition, to measure the liposome encapsulation efficiency accurately, we establish a unique high-performance liquid chromatography technique in which an alkaline buffer mobile phase is used to prevent apigenin precipitation in the column;. salt is added to separate lipid particles from the aqeuous phase. Our results demonstrate that apigenin encapsulation efficiency is nearly 98% that is remarkably higher than any other reported value for encapsulation of this compound. In addition, the average particle size of these liposomes is 158.9 ± 6.1 nm that is suitable for the formulation of many food products, such as fortified fruit juice. The encapsulation method developed in this study, therefore have a high potential for the production of innovative, functional foods or nutraceutical products. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Ganglioside inserted into PEGylated liposome attenuates anti-PEG immunity.

    PubMed

    Mima, Yu; Abu Lila, Amr S; Shimizu, Taro; Ukawa, Masami; Ando, Hidenori; Kurata, Yasuko; Ishida, Tatsuhiro

    2017-03-28

    Despite the clinical introduction of a vast number of polyethylene glycol (PEG)-conjugated therapeutics, conjugated PEG is also known for an unfortunate inclination toward immunogenicity. Immunogenicity of PEG, manifested by the robust production of anti-PEG IgM, is known to compromise the therapeutic efficacy and/or reduce the tolerance of PEGylated therapeutics. In the present study, we inserted ganglioside into the membrane of PEGylated liposome (PL) to prepare ganglioside-modified PEGylated liposomes (G-PL), and investigated its efficacy in attenuating the anti-PEG IgM response against PL. A single intravenous injection of G-PL significantly attenuated the anti-PEG IgM production, compared with that of naïve PL. In addition, pretreatment with G-PL substantially alleviated the anti-PEG IgM response elicited by a subsequent dose of PL, presumably via inducing B cell tolerance, and as a consequence, this modification abrogated/attenuated the incidence of the rapid clearance of subsequently administrated PL. These results indicate that incorporating gangliosides in PEGylated liposome membrane not only prevents the immunogenicity of PEG but also induces the tolerance of B cells to subsequent doses of the immunogenic PL. Consequently, liposomal membrane modification with ganglioside might represent a promising approach to attenuating the immunogenicity of PEGylated liposomes while preserving their therapeutic efficacy, particularly upon repeated administration.

  5. Ultrasound Induced Fluorescence of Nanoscale Liposome Contrast Agents

    PubMed Central

    Zhang, Qimei; Morgan, Stephen P.; O’Shea, Paul; Mather, Melissa L.

    2016-01-01

    A new imaging contrast agent is reported that provides an increased fluorescent signal upon application of ultrasound (US). Liposomes containing lipids labelled with pyrene were optically excited and the excimer fluorescence emission intensity was detected in the absence and presence of an ultrasound field using an acousto-fluorescence setup. The acousto-fluorescence dynamics of liposomes containing lipids with pyrene labelled on the fatty acid tail group (PyPC) and the head group (PyPE) were compared. An increase in excimer emission intensity following exposure to US was observed for both cases studied. The increased intensity and time constants were found to be different for the PyPC and PyPE systems, and dependent on the applied US pressure and exposure time. The greatest change in fluorescence intensity (130%) and smallest rise time constant (0.33 s) are achieved through the use of PyPC labelled liposomes. The mechanism underlying the observed increase of the excimer emission intensity in PyPC labelled liposomes is proposed to arise from the “wagging” of acyl chains which involves fast response and requires lower US pressure. This is accompanied by increased lipid lateral diffusivity at higher ultrasound pressures, a mechanism that is also active in the PyPE labelled liposomes. PMID:27467748

  6. Development and characterization of liposomal doxorubicin hydrochloride with palm oil.

    PubMed

    Sabeti, Bahareh; Noordin, Mohamed Ibrahim; Mohd, Shaharuddin; Hashim, Rosnani; Dahlan, Afendi; Javar, Hamid Akbari

    2014-01-01

    The usage of natural products in pharmaceuticals has steadily seen improvements over the last decade, and this study focuses on the utilization of palm oil in formulating liposomal doxorubicin (Dox). The liposomal form of Dox generally minimizes toxicity and enhances target delivery actions. Taking into account the antiproliferative and antioxidant properties of palm oil, the aim of this study is to design and characterize a new liposomal Dox by replacing phosphatidylcholine with 5% and 10% palm oil content. Liposomes were formed using the freeze_thaw method, and Dox was loaded through pH gradient technique and characterized through in vitro and ex vivo terms. Based on TEM images, large lamellar vesicles (LUV) were formed, with sizes of 438 and 453 nm, having polydispersity index of 0.21 ± 0.8 and 0.22 ± 1.3 and zeta potentials of about -31 and -32 mV, respectively. In both formulations, the entrapment efficiency was about 99%, and whole Dox was released through 96 hours in PBS (pH = 7.4) at 37°C. Comparing cytotoxicity and cellular uptake of LUV with Caelyx(R) on MCF7 and MDA-MBA 231 breast cancer cell lines indicated suitable uptake and lower IC50 of the prepared liposomes.

  7. Development and Characterization of Liposomal Doxorubicin Hydrochloride with Palm Oil

    PubMed Central

    Sabeti, Bahareh; Noordin, Mohamed Ibrahim; Mohd, Shaharuddin; Hashim, Rosnani; Akbari Javar, Hamid

    2014-01-01

    The usage of natural products in pharmaceuticals has steadily seen improvements over the last decade, and this study focuses on the utilization of palm oil in formulating liposomal doxorubicin (Dox). The liposomal form of Dox generally minimizes toxicity and enhances target delivery actions. Taking into account the antiproliferative and antioxidant properties of palm oil, the aim of this study is to design and characterize a new liposomal Dox by replacing phosphatidylcholine with 5% and 10% palm oil content. Liposomes were formed using the freeze_thaw method, and Dox was loaded through pH gradient technique and characterized through in vitro and ex vivo terms. Based on TEM images, large lamellar vesicles (LUV) were formed, with sizes of 438 and 453 nm, having polydispersity index of 0.21 ± 0.8 and 0.22 ± 1.3 and zeta potentials of about −31 and −32 mV, respectively. In both formulations, the entrapment efficiency was about 99%, and whole Dox was released through 96 hours in PBS (pH = 7.4) at 37°C. Comparing cytotoxicity and cellular uptake of LUV with CaelyxR on MCF7 and MDA-MBA 231 breast cancer cell lines indicated suitable uptake and lower IC50 of the prepared liposomes. PMID:24795894

  8. Liposomes self-assembled from electrosprayed composite microparticles

    NASA Astrophysics Data System (ADS)

    Yu, Deng-Guang; Yang, Jun-He; Wang, Xia; Tian, Feng

    2012-03-01

    Composite microparticles, consisting of polyvinylpyrrolidone (PVP), naproxen (NAP) and lecithin (PC), have been successfully prepared using an electrospraying process and exploited as templates to manipulate molecular self-assembly for the synthesis of liposomes in situ. Field emission scanning electron microscope (FESEM) and transmission electron microscope (TEM) observations demonstrate that the microparticles have an average diameter of 960 ± 140 nm and a homogeneous structure. X-ray diffraction (XRD) patterns, differential scanning calorimetry (DSC) and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) results verify that the building blocks NAP and PC are scattered in the polymer matrix in a molecular way owing to the very fast drying of the electrospraying process and the favorable secondary interactions among the components. FESEM, scanning probe microscope (SPM) and TEM observations demonstrate that the liposomes can be achieved through molecular self-assembly in situ when the microparticles contact water thanks to ‘like prefers like’ and by means of the confinement effect of the microparticles. The liposomes have an encapsulation rate of 91.3%, and 80.7% of the drug in the liposomes can be freed into the dissolution medium in a sustained way and by a diffusion mechanism over a period of 24 h. The developed strategy not only provides a new, facile, and effective method to assemble and organize molecules of multiple components into liposomes with electrosprayed microparticles as templates, but also opens a new avenue for nanofabrication in a step-by-step and controllable way.

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

    PubMed

    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.

  10. Liposomal formulations of prilocaine, lidocaine and mepivacaine prolong analgesic duration.

    PubMed

    Cereda, Cíntia Maria Saia; Brunetto, Giovana Bruschini; de Araújo, Daniele Ribeiro; de Paula, Eneida

    2006-11-01

    A laboratory investigation was undertaken to compare the in vivo antinociceptive effects of 2% liposomal formulations of prilocaine (PLC), lidocaine (LDC) and mepivacaine (MVC) compared to plain solutions of each of these three local anesthetics. Large unilamellar vesicles were prepared by extrusion (400 nm), at pH 7.4. The membrane/water partition coefficients were obtained from encapsulation efficiency values, after incorporation of each local anesthetic to the vesicles. The anesthetic effect of each liposomal formulation was compared to the respective local anesthetic solution in water, using the infraorbital nerve-blockade test, in rats. The partition coefficients were: 57 for PLC, 114 for LDC and 93 for MVC. In vivo results showed that local anesthetic-free liposomes, used as control, had no analgesic effect. In contrast, the encapsulated formulations induced increased intensities of total anesthetic effect (35.3%, 26.1% and 57.1%) and time for recovery (percentage increases of 30%, 23.1% and 56%), respectively, for PLC, LDC and MVC when compared to the plain solutions (P < 0.01). These results indicate that liposomes provide effective drug-delivery systems for intermediate-duration local anesthetics. Mepivacaine was affected to the greatest extent, while LDC benefited least from liposome encapsulation, possibly due to greater vasodilatory properties of LDC.

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

    PubMed Central

    Kneidl, Barbara; Peller, Michael; Winter, Gerhard; Lindner, Lars H; Hossann, Martin

    2014-01-01

    Thermosensitive liposomes are a promising tool for external targeting of drugs to solid tumors when used in combination with local hyperthermia or high intensity focused ultrasound. In vivo results have demonstrated strong evidence that external targeting is superior over passive targeting achieved by highly stable long-circulating drug formulations like PEGylated liposomal doxorubicin. Up to March 2014, the Web of Science listed 371 original papers in this field, with 45 in 2013 alone. Several formulations have been developed since 1978, with lysolipid-containing, low temperature-sensitive liposomes currently under clinical investigation. This review summarizes the historical development and effects of particular phospholipids and surfactants on the biophysical properties and in vivo efficacy of thermosensitive liposome formulations. Further, treatment strategies for solid tumors are discussed. Here we focus on temperature-triggered intravascular and interstitial drug release. Drug delivery guided by magnetic resonance imaging further adds the possibility of performing online monitoring of a heating focus to calculate locally released drug concentrations and to externally control drug release by steering the heating volume and power. The combination of external targeting with thermosensitive liposomes and magnetic resonance-guided drug delivery will be the unique characteristic of this nanotechnology approach in medicine. PMID:25258529

  12. Chitosan coated liposomes as an innovative nanocarrier for drugs.

    PubMed

    Gonçalves, Manuela C F; Mertins, Omar; Pohlmann, Adriana R; Silveira, Nádya P; Guterres, Sílvia S

    2012-04-01

    Chitosomes are chitosan coated liposomes that represent an alternative to conventional liposomes since they present better stability and bioadhesivity. The aim of this work was to develop and evaluate the physico-chemical stability of melatonin (MEL)-loaded chitosomes as well as to compare their properties with that of MEL loaded liposomes. Structural characteristics of nanovesicles were also studied by dynamic light scattering and small angle X-ray scattering. The liposome and chitosome suspensions presented mean diameters between 150 nm and 254 nm, polydispersity indexes around 0.4, zeta potential values between -38 mV and -28 mV, pH values close to 4.0, MEL content close to 100% and encapsulation efficiency between 34.4% and 60.8%. Small angle X-rays scattering showed the presence of unilamelar structures, which were also observed by transmission electronic microscopy. Stability studies focusing on the particle diameter indicated that, within 90 days, the liposome suspensions had a decrease in mean diameter values and in polydispersity indexes, but no alterations were detected in zeta potentials and MEL content. The chitosome suspensions remained stable in relation to these parameters during 90 days. Multiple light scattering analysis (Turbiscan LAb) corroborated the the findings in the stability studies. The result sets pointed out the physico-chemical stability of chitosomes and the chitosan influence in their supramolecular structure.

  13. A "Dock and Lock" Approach to Preparation of Targeted Liposomes.

    PubMed

    Backer, Marina V; Backer, Joseph M

    2017-01-01

    We developed a strategy for covalent coupling of targeting proteins to liposomes decorated with a standard adapter protein. This strategy is based on "dock and lock" interactions between two mutated fragments of human RNase I, a 1-15 aa fragment with the R4C amino acid substitution (Cys-tag), and a 21-127-aa fragment with the V118C substitution, (Ad-C). Upon binding to each other, Cys-tag and Ad-C spontaneously form a disulfide bond between the complementary 4C and 118C residues. Therefore, any targeting protein expressed with Cys-tag can be easily coupled to liposomes decorated with Ad-C. Here we describe the preparation of Ad-liposomes followed by coupling them to two Cys-tagged targeted proteins, human vascular endothelial growth factor expressed with N-terminal Cys-tag and a 254-aa long N-terminal fragment of anthrax lethal factor carrying C-terminal Cys-tag. Both proteins retain functional activity after coupling to Ad-C-decorated drug-loaded liposomes. We expect that our "dock and lock" strategy will open new opportunities for development of targeted therapeutic liposomes for research and clinical use.

  14. Detection of Liposome Membrane Viscosity Perturbations with Ratiometric Molecular Rotors

    PubMed Central

    Nipper, Matthew E.; Dakanali, Marianna; Theodorakis, Emmanuel

    2011-01-01

    Molecular rotors are a form of fluorescent intramolecular charge-transfer complexes that can undergo intramolecular twisting motion upon photoexcitation. Twisted-state formation leads to non-radiative relaxation that competes with fluorescence emission. In bulk solutions, these molecules exhibit a viscosity-dependent quantum yield. On the molecular scale, the fluorescence emission is a function of the local free volume, which in turn is related to the local microviscosity. Membrane viscosity, and the inverse; fluidity, are characteristic terms used to describe the ease of movement withing the membrane. Often, changes in membrane viscosity govern intracellular processes and are indicative of a disease state. Molecular rotors have been used to investigate viscosity changes in liposomes and cells, but accuracy is affected by local concentration gradients and sample optical properties. We have developed self-calibrating ratiometric molecular rotors to overcome this challenge and integrated the new molecules into a DLPC liposome model exposed to the membrane-fluidizing agent propanol. We show that the ratiometric emission intensity linearly decreases with the pentanol exposure and that the ratiometric intensity is widely independent of the total liposome concentration. Conversely, dye concentration inside liposomes influences the sensitivity of the system. We suggest that the new self-calibrating dyes can be used for real-time viscosity sensing in liposome systems with the advantages of lifetime measurements, but with low-cost steady-state instrumentation. PMID:21354253

  15. Liposomal Encapsulation Enzymes: From Medical Applications to Kinetic Characteristics.

    PubMed

    Jahadi, M; Khosravi-Darani, K

    2017-01-01

    Liposomes and nanoliposomes as small vesicles composed of phospholipid bilayer (entrapping one or more hydrophilic or lipophilic components) have recently found several potential applications in medicine and food industry. These vesicles may protect the core materials from moisture, heat and other extreme conditions. They may also provide controlled release of various bioactive agents, including food ingredients at the right place and time. Potential applications of enzyme-loaded liposomes are in the medical or biomedical field, particularly for the enzymereplacement therapy, as well as cheese industry for production of functional foods with improved health beneficial impacts on the consumer. Encapsulation process has a recondite impact on enzymes. In fact, liposome preparation techniques may alter the pH and temperature optima, affinity of the enzyme to substrate (Km), and maximum rate of reaction (Vmax). In addition, in this paper, the impact of process variables on the kinetic characteristics of enzymes encapsulated in liposomes was investigated. Also, the effects of enzyme entrapment in liposomes, prepared by different methods, on the catalytic efficiency of enzyme, as well as its kinetic properties and stability compared to native (free) enzymes has been reviewed.

  16. Carriers for skin delivery of trihexyphenidyl HCl: ethosomes vs. liposomes.

    PubMed

    Dayan, N; Touitou, E

    2000-09-01

    The purpose of this work was to characterize a novel ethosomal carrier containing trihexyphenidyl HCl (THP) and to investigate the delivery of THP from ethosomes versus classic liposomes. THP-ethosomal systems were shown by electron microscopy to contain small, phospholipid vesicles. As the THP concentration was increased from 0 to 3%, the size of the vesicles decreased from 154 to 90 nm. This is most likely due to the surface activity of THP (critical micelle concentration of 5.9 mg/ml), as measured in this work. In addition, the ethosome zeta potential value increased as a function of THP concentration, from -4.5 to +10.4 when the THP concentration was increased from 0 to 3%. In contrast, THP liposomes were much larger and their charge was not affected by THP. When compared with standard liposomes, ethosomes had a higher entrapment capacity and a greater ability to deliver entrapped fluorescent probe to the deeper layers of skin. The flux of THP through nude mouse skin from THP ethosomes (0.21 mg/cm2 h) was 87, 51 and 4.5 times higher than from liposomes, phosphate buffer and hydroethanolic solution, respectively (p < 0.01). The quantity of THP remaining in the skin at the end of the 18-h experiment was statistically significantly greater from the ethosomal system than from liposomes or a control hydroethanolic solution. Our results indicate that the ethosomal THP system may be a promising candidate for transdermal delivery of THP.

  17. Liposomes- and ethosomes-associated distamycins: a comparative study.

    PubMed

    Cortesi, Rita; Romagnoli, Romeo; Drechsler, Markus; Menegatti, Enea; Zaid, Abdel N; Ravani, Laura; Esposito, Elisabetta

    2010-12-01

    The present article describes a comparative study of the performances of liposomes and ethosomes as specialized delivery systems for distamycin A (DA) and two of its derivatives. Liposomes and ethosomes were prepared by classical methods, extruded through polycarbonate filters, and characterized in terms of dimensions, morphology, and encapsulation efficiency. It was found that DA was associated with vesicles (either liposomes or ethosomes) by around 16.0%, while both derivatives of DA showed a percentage of association around 80% in the case of liposomes and around 50% in the case of ethosomes. In vitro antiproliferative activity experiments performed on cultured human and mouse leukemic cells demonstrated that vesicles were able to increase the activity of both derivatives of DA. In addition, it was demonstrated that the aging of both liposomes- and ethosomes-associated distamycin suspensions did not heavily influence the vesicle size, while all samples showed a relevant drug leakage with time. Moreover, according to the different physicochemical characteristics of DA and its derivatives (i.e., log P), vesicle-associated DA showed the highest loss of drug with respect to both its derivatives. In conclusion, the enhancement of drug activity expressed by these specialized delivery systems-associated DD could be interesting to obtain an efficient therapeutic effect aimed at reducing or minimizing toxic effects occurring with distamycins administration.

  18. Formulation and stabilization of norfloxacin in liposomal preparations.

    PubMed

    Ahmad, Iqbal; Arsalan, Adeel; Ali, Syed Abid; Bano, Raheela; Munir, Iqra; Sabah, Arif

    2016-08-25

    A number of liposomal preparations of norfloxacin (NF) containing variable concentrations of phosphatidylcholine (PC) (10.8-16.2mM) have been formulated and an entrapment of NF to the extent of 41.7-56.2% was achieved. The values of apparent first-order rate constants (kobs) for the photodegradation of NF in liposomes (pH7.4) lie in the range of 1.05-2.40×10(-3)min(-1) compared to a value of 8.13×10(-3)min(-1) for the photodegradation of NF in aqueous solution (pH7.4). The values of kobs are a linear function of PC concentration indicating an interaction of PC and NF during the reaction. The second-order rate constant for the photochemical interaction of PC and NF has been determined as 8.92×10(-2)M(-1)min(-1). Fluorescence measurements on NF in liposomes indicate a decrease in fluorescence with an increase in PC concentration as a result of formation of NF(-) species which exhibits poor fluorescence. Dynamic light scattering has shown an increase in the size of NF encapsulated liposomes with an increase in PC concentration. The stabilization of NF in liposomes is achieved by the formation of a charge-transfer complex between NF and PC. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Assembly of liposomes controlled by triple helix formation.

    PubMed

    Jakobsen, Ulla; Vogel, Stefan

    2013-09-18

    Attachment of DNA to the surface of different solid nanoparticles (e.g., gold and silica nanoparticles) is well established, and a number of DNA-modified solid nanoparticle systems have been applied to thermal denaturation analysis of oligonucleotides. We report herein the noncovalent immobilization of oligonucleotides on the surface of soft nanoparticles (i.e., liposomes) and the subsequent controlled assembly by DNA triple helix formation. The noncovalent approach avoids tedious surface chemistry and necessary purification procedures and can simplify and extend the available methodology for the otherwise difficult thermal denaturation analysis of complex triple helical DNA assemblies. The approach is based on lipid modified triplex forming oligonucleotides (TFOs) which control the assembly of liposomes in solution in the presence of single- or double-stranded DNA targets. The thermal denaturation analysis is monitored by ultraviolet spectroscopy at submicromolar concentrations and compared to regular thermal denaturation assays in the absence of liposomes. We report on triplex forming oligonucleotides (TFOs) based on DNA and locked nucleic acid (LNA)/DNA hybrid building blocks and different target sequences (G or C-rich) to explore the applicability of the method for different triple helical assembly modes. We demonstrate advantages and limitations of the approach and show the reversible and reproducible formation of liposome aggregates during thermal denaturation cycles. Nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS) show independently from ultraviolet spectroscopy experiments the formation of liposome aggregates.

  20. Chemically triggered release of 5-aminolevulinic acid from liposomes*

    PubMed Central

    Plaunt, Adam J.; Harmatys, Kara M.; Hendrie, Kyle A.; Musso, Anthony J.

    2014-01-01

    5-Aminolevulinic acid (5-ALA), a prodrug of Protoporphyrin IX (PpIX), is used for photodynamic therapy of several medical conditions, and as an adjunct for fluorescence guided surgery. The clinical problem of patient photosensitivity after systemic administration could likely be ameliorated if the 5-ALA was delivered more selectivity to the treatment site. Liposomal formulations are inherently attractive as targeted delivery vehicles but it is hard to regulate the spatiotemporal release of aqueous contents from a liposome. Here, we demonstrate chemically triggered leakage of 5-ALA from stealth liposomes in the presence of cell culture. The chemical trigger is a zinc(II)-dipicolylamine (ZnBDPA) coordination complex that selectively targets liposome membranes containing a small amount of anionic phosphatidylserine. Systematic screening of several ZnBDPA complexes uncovered a compound with excellent performance in biological media. Cell culture studies showed triggered release of 5-ALA from stealth liposomes followed by uptake into neighboring mammalian cells and intracellular biosynthesis to form fluorescent PpIX. PMID:25414791

  1. Detection of liposome membrane viscosity perturbations with ratiometric molecular rotors.

    PubMed

    Nipper, Matthew E; Dakanali, Marianna; Theodorakis, Emmanuel; Haidekker, Mark A

    2011-06-01

    Molecular rotors are a form of fluorescent intramolecular charge-transfer complexes that can undergo intramolecular twisting motion upon photoexcitation. Twisted-state formation leads to non-radiative relaxation that competes with fluorescence emission. In bulk solutions, these molecules exhibit a viscosity-dependent quantum yield. On the molecular scale, the fluorescence emission is a function of the local free volume, which in turn is related to the local micro-viscosity. Membrane viscosity, and the inverse; fluidity, are characteristic terms used to describe the ease of movement withing the membrane. Often, changes in membrane viscosity govern intracellular processes and are indicative of a disease state. Molecular rotors have been used to investigate viscosity changes in liposomes and cells, but accuracy is affected by local concentration gradients and sample optical properties. We have developed self-calibrating ratiometric molecular rotors to overcome this challenge and integrated the new molecules into a DLPC liposome model exposed to the membrane-fluidizing agent propanol. We show that the ratiometric emission intensity linearly decreases with the propanol exposure and that the ratiometric intensity is widely independent of the total liposome concentration. Conversely, dye concentration inside liposomes influences the sensitivity of the system. We suggest that the new self-calibrating dyes can be used for real-time viscosity sensing in liposome systems with the advantages of lifetime measurements, but with low-cost steady-state instrumentation.

  2. Crosslinked Multilamellar Liposomes for Controlled Delivery of Anticancer Drugs

    PubMed Central

    Joo, Kye-Il; Xiao, Liang; Liu, Shuanglong; Liu, Yarong; Lee, Chi-Lin; Conti, Peter S.; Wong, Michael K.; Li, Zibo; Wang, Pin

    2014-01-01

    Liposomes constitute one of the most popular nanocarriers for the delivery of cancer therapeutics. However, since their potency is limited by incomplete drug release and inherent instability in the presence of serum components, their poor delivery occurs in certain circumstances. In this study, we address these shortcomings and demonstrate an alternative liposomal formulation, termed crosslinked multilamellar liposome (CML). With its properties of improved sustainable drug release kinetics and enhanced vesicle stability, CML can achieve controlled delivery of cancer therapeutics. CML stably encapsulated the anticancer drug doxorubicin (Dox) in the vesicle and exhibited a remarkably controlled rate of release compared to that of the unilamellar liposome (UL) with the same lipid composition or Doxil-like liposome (DLL). Our imaging study demonstrated that the CMLs were mainly internalized through a caveolin-dependent pathway and were further trafficked through the endosome-lysosome compartments. Furthermore, in vivo experiments showed that the CML-Dox formulation reduced systemic toxicity and significantly improved therapeutic activity in inhibiting tumor growth compared to that of UL-Dox or DLL-Dox. This drug packaging technology may therefore provide a new treatment option to better manage cancer and other diseases. PMID:23375392

  3. Preparation and evaluation of semi-permanent hair dyes liposome.

    PubMed

    Chen, Lichou; Chen, Chonyu

    2011-01-01

    This study used phospholipids from fresh egg yolks to prepare liposome-encapsulated semi-permanent hair dyes in different pH buffer solutions and evaluated the functions and colour fastness to washing of the dyes. The extraction ratio of egg yolk phospholipids was 5%, and the purity was 91.8%. Empty liposome solutions were then prepared using high-speed homogenizer with particle size 219-848 nm. After being stored at 4 °C for 28 days, the average particle size of the liposome-encapsulated dye formulas increased from 1.36-1.92 µm to 1.99-2.38 µm. The ΔE colour difference values of the five hair extension sets dyed with the control group and hair dyes on the market were of the range 6.56-13.39 after eight times of washing, whereas the ΔE values of the four hair extension sets dyed with the liposome-encapsulated dyes were of the range 3.56-5.21 after eight times of washing. The liposome-encapsulated dye at pH 3 showed the best result.

  4. Application of Liposomes in Treatment of Rheumatoid Arthritis: Quo Vadis

    PubMed Central

    Singh, Sachin Kumar; Gulati, Monica

    2014-01-01

    The most common treatments for rheumatoid arthritis include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease modifying antirheumatic drugs (DMARDs), and some biological agents. However, none of the treatments available is able to achieve the ultimate goal of treatment, that is, drug-free remission. This limitation has shifted the focus of treatment to delivery strategies with an ability to deliver the drugs into the synovial cavity in the proper dosage while mitigating side effects to other tissues. A number of approaches like microemulsions, microspheres, liposomes, microballoons, cocrystals, nanoemulsions, dendrimers, microsponges, and so forth, have been used for intrasynovial delivery of these drugs. Amongst these, liposomes have proven to be very effective for retaining the drug in the synovial cavity by virtue of their size and chemical composition. The fast clearance of intra-synovially administered drugs can be overcome by use of liposomes leading to increased uptake of drugs by the target synovial cells, which in turn reduces the exposure of nontarget sites and eliminates most of the undesirable effects associated with therapy. This review focuses on the use of liposomes in treatment of rheumatoid arthritis and summarizes data relating to the liposome formulations of various drugs. It also discusses emerging trends of this promising technology. PMID:24688450

  5. Ultrasonic energy in liposome production: process modelling and size calculation.

    PubMed

    Barba, A A; Bochicchio, S; Lamberti, G; Dalmoro, A

    2014-04-21

    The use of liposomes in several fields of biotechnology, as well as in pharmaceutical and food sciences is continuously increasing. Liposomes can be used as carriers for drugs and other active molecules. Among other characteristics, one of the main features relevant to their target applications is the liposome size. The size of liposomes, which is determined during the production process, decreases due to the addition of energy. The energy is used to break the lipid bilayer into smaller pieces, then these pieces close themselves in spherical structures. In this work, the mechanisms of rupture of the lipid bilayer and the formation of spheres were modelled, accounting for how the energy, supplied by ultrasonic radiation, is stored within the layers, as the elastic energy due to the curvature and as the tension energy due to the edge, and to account for the kinetics of the bending phenomenon. An algorithm to solve the model equations was designed and the relative calculation code was written. A dedicated preparation protocol, which involves active periods during which the energy is supplied and passive periods during which the energy supply is set to zero, was defined and applied. The model predictions compare well with the experimental results, by using the energy supply rate and the time constant as fitting parameters. Working with liposomes of different sizes as the starting point of the experiments, the key parameter is the ratio between the energy supply rate and the initial surface area.

  6. Design considerations for liposomal vaccines: Influence of formulation parameters on antibody and cell-mediated immune responses to liposome associated antigens

    PubMed Central

    Watson, Douglas S.; Endsley, Aaron N.; Huang, Leaf

    2012-01-01

    Liposomes (phospholipid bilayer vesicles) are versatile and robust delivery systems for induction of antibody and T lymphocyte responses to associated subunit antigens. In the last 15 years, liposome vaccine technology has matured and now several vaccines containing liposome-based adjuvants have been approved for human use or have reached late stages of clinical evaluation. Given the intensifying interest in liposome-based vaccines, it is important to understand precisely how liposomes interact with the immune system and stimulate immunity. It has become clear that the physicochemical properties of liposomal vaccines – method of antigen attachment, lipid composition, bilayer fluidity, particle charge, and other properties – exert dramatic effects on the resulting immune response. Here, we present a comprehensive review of the physicochemical properties of liposomal vaccines and how they influence immune responses. A discussion of novel and emerging immunomodulators that are suitable for inclusion in liposomal vaccines is also presented. Through a comprehensive analysis of the body of liposomal vaccine literature, we enumerate a series of principles that can guide the rational design of liposomal vaccines to elicit immune responses of a desired magnitude and quality. We also identify major unanswered questions in the field, pointing the direction for future study. PMID:22306376

  7. Reversible and irreversible aggregation of magnetic liposomes.

    PubMed

    García-Jimeno, Sonia; Estelrich, Joan; Callejas-Fernández, José; Roldán-Vargas, Sándalo

    2017-10-12

    Understanding stabilization and aggregation in magnetic nanoparticle systems is crucial to optimizing the functionality of these systems in real physiological applications. Here we address this problem for a specific, yet representative, system. We present an experimental and analytical study on the aggregation of superparamagnetic liposomes in suspension in the presence of a controllable external magnetic field. We study the aggregation kinetics and report an intermediate time power law evolution and a long time stationary value for the average aggregate diffusion coefficient, both depending on the magnetic field intensity. We then show that the long time aggregate structure is fractal with a fractal dimension that decreases upon increasing the magnetic field intensity. By scaling arguments we also establish an analytical relation between the aggregate fractal dimension and the power law exponent controlling the aggregation kinetics. This relation is indeed independent on the magnetic field intensity. Despite the superparamagnetic character of our particles, we further prove the existence of a population of surviving aggregates able to maintain their integrity after switching off the external magnetic field. Finally, we suggest a schematic interaction scenario to rationalize the observed coexistence between reversible and irreversible aggregation.

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

    PubMed Central

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

    2016-01-01

    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 obtain required parts; 2) assembly of the dialyzer; and 3) sealing the dialyzer with epoxy. Preparation of the dialyser takes about 1.5 h, not including overnight epoxy curing. Each round of dialysis takes 1–24 h, depending on the analyte and membrane employed. We previously used the dialyzer for small-volume nonenzymatic RNA synthesis reactions inside fatty acid vesicles. In this protocol, we demonstrate other applications, including removal of unencapsulated calcein from vesicles, remote loading, and vesicle microscopy. PMID:26020615

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

    PubMed

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

    2012-06-01

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

  10. An efficient PEGylated liposomal nanocarrier containing cell-penetrating peptide and pH-sensitive hydrazone bond for enhancing tumor-targeted drug delivery

    PubMed Central

    Ding, Yuan; Sun, Dan; Wang, Gui-Ling; Yang, Hong-Ge; Xu, Hai-Feng; Chen, Jian-Hua; Xie, Ying; Wang, Zhi-Qiang

    2015-01-01

    Cell-penetrating peptides (CPPs) as small molecular transporters with abilities of cell penetrating, internalization, and endosomal escape have potential prospect in drug delivery systems. However, a bottleneck hampering their application is the poor specificity for cells. By utilizing the function of hydration shell of polyethylene glycol (PEG) and acid sensitivity of hydrazone bond, we constructed a kind of CPP-modified pH-sensitive PEGylated liposomes (CPPL) to improve the selectivity of these peptides for tumor targeting. In CPPL, CPP was directly attached to liposome surfaces via coupling with stearate (STR) to avoid the hindrance of PEG as a linker on the penetrating efficiency of CPP. A PEG derivative by conjugating PEG with STR via acid-degradable hydrazone bond (PEG2000-Hz-STR, PHS) was synthesized. High-performance liquid chromatography and flow cytometry demonstrated that PHS was stable at normal neutral conditions and PEG could be completely cleaved from liposome surface to expose CPP under acidic environments in tumor. An optimal CPP density on liposomes was screened to guaranty a maximum targeting efficiency on tumor cells as well as not being captured by normal cells that consequently lead to a long circulation in blood. In vitro and in vivo studies indicated, in 4 mol% CPP of lipid modified system, that CPP exerted higher efficiency on internalizing the liposomes into targeted subcellular compartments while remaining inactive and free from opsonins at a maximum extent in systemic circulation. The 4% CPPL as a drug delivery system will have great potential in the clinical application of anticancer drugs in future. PMID:26491292

  11. Effect of space length of mannose ligand on uptake of mannosylated liposome in RAW 264.7 cells: In vitro and in vivo studies.

    PubMed

    Jeong, Hwan-Seok; Na, Kyung Sook; Hwang, Hyosook; Oh, Phil-Sun; Kim, Dong Hyun; Lim, Seok Tae; Sohn, Myung-Hee; Jeong, Hwan-Jeong

    2014-12-01

    The most widely used method for increasing uptake on macrophage is specific targeting for mannose receptor (MR) presented on macrophages. Efficiency of the uptake for MR is influenced by the space length and flexibility of mannose ligand in liposome (LP). We prepared mannosylated liposomes (M-EGn-LP-ICG) encapsulated indocyanine green (ICG) with mannose ligand of various ethylene glycol units (EG), LP-ICG, and mannosylated liposome (M-LP-ICG) incorporated with p-aminophenyl-α-d-mannopyranoside. We studied the effect of space length of the mannose ligand in vitro and in vivo with prepared liposomes. A space length of two ethylene glycol units at least was needed for uptake by macrophages and the uptake was increased as the space length increased up to EG4. We measured near-infrared (NIR) fluorescence intensity by ICG and the fluorescence value of cell-associated N-(4-nitrobenzo-2-oxa-1,3-diazole) (NBD) in liposome after cellular uptake. M-EG4-LP-ICG showed lower NIR fluorescence intensity but higher NBD fluorescence value than M-LP-ICG. The result of pre-treatment with d(+)-mannose as an inhibitor showed significant decreasing in uptake of mannosylated LP-ICG but no difference in LP-ICG. These were explained that mannosylated LP-ICG was taken up by macrophages through the MR and M-EG4-LP-ICG showed more specific uptake than M-LP-ICG. We obtained images as time passed in the NIR range after intravenous administration using a Balb/c mouse with inflammatory model. The results showed high uptake in liver at early time and rapid degradation of mannosylated LP-ICG. M-EG4-LP-ICG was more selectively taken up by macrophages than M-LP-ICG.

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

    SciTech Connect

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

    1980-08-01

    Ultraviolet radiation and sunlight caused lipid peroxidation in the liposomal membrane (as detected by measurement of the oxidation index, A/sub 233//A/sub 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.

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

    PubMed

    Federico, Cinzia; Morittu, Valeria M; Britti, Domenico; Trapasso, Elena; Cosco, Donato

    2012-01-01

    This review describes the strategies used in recent years to improve the biopharmaceutical properties of gemcitabine, a nucleoside analog deoxycytidine antimetabolite characterized by activity against many kinds of tumors, by means of liposomal devices. The main limitation of using this active compound is the rapid inactivation of deoxycytidine deaminase following administration in vivo. Consequently, different strategies based on its encapsulation/complexation in innovative vesicular colloidal carriers have been investigated, with interesting results in terms of increased pharmacological activity, plasma half-life, and tumor localization, in addition to decreased side effects. This review focuses on the specific approaches used, based on the encapsulation of gemcitabine in liposomes, with particular attention to the results obtained during the last 5 years. These approaches represent a valid starting point in the attempt to obtain a novel, commercializable drug formulation as already achieved for liposomal doxorubicin (Doxil(®), Caelyx(®)).

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

    PubMed Central

    Perche, Federico; Torchilin, Vladimir P.

    2013-01-01

    Liposomes are delivery systems that have been used to formulate a vast variety of therapeutic and imaging agents for the past several decades. They have significant advantages over their free forms in terms of pharmacokinetics, sensitivity for cancer diagnosis and therapeutic efficacy. The multifactorial nature of cancer and the complex physiology of the tumor microenvironment require the development of multifunctional nanocarriers. Multifunctional liposomal nanocarriers should combine long blood circulation to improve pharmacokinetics of the loaded agent and selective distribution to the tumor lesion relative to healthy tissues, remote-controlled or tumor stimuli-sensitive extravasation from blood at the tumor's vicinity, internalization motifs to move from tumor bounds and/or tumor intercellular space to the cytoplasm of cancer cells for effective tumor cell killing. This review will focus on current strategies used for cancer detection and therapy using liposomes with special attention to combination therapies. PMID:23533772

  15. Liposomal amphotericin B and leishmaniasis: dose and response.

    PubMed

    Sundar, Shyam; Chakravarty, Jaya

    2010-05-01

    Liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL). It is the treatment of choice for immunocompetent patients in the Mediterranean region and the preferred drug for HIV/VL co-infection. Although there is a regional variation in the susceptibility of the parasite a total dose of 20 mg/kg is effective in immunocompetent patients. Randomized clinical trials of liposomal amphotericin B in the treatment and secondary prophylaxis of HIV-VL coinfected patients is urgently needed to optimize treatment in this subset. With the availability of Liposomal amphotericin B at a preferential pricing in the endemic areas, short course combination therapy can become a viable alternative.

  16. Second generation liposomal cancer therapeutics: transition from laboratory to clinic.

    PubMed

    Sen, Kacoli; Mandal, Mahitosh

    2013-05-01

    Recent innovations and developments in nanotechnology have revolutionized cancer therapeutics. Engineered nanomaterials are the current workhorses in the emerging field of cancer nano-therapeutics. Lipid vesicles bearing anti-tumor drugs have turned out to be a clinically feasible and promising nano-therapeutic approach to treat cancer. Efficient entrapment of therapeutics, biocompatibility, biodegradability, low systemic toxicity, low immunogenicity and ability to bypass multidrug resistance mechanisms has made liposomes a versatile drug/gene delivery system in cancer chemotherapy. The present review attempts to explore the recent key advances in liposomal research and the vast arsenal of liposomal formulations currently being utilized in treatment and diagnosis of cancer. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Liposomal extended-release bupivacaine for postsurgical analgesia

    PubMed Central

    Lambrechts, Mark; O’Brien, Michael J; Savoie, Felix H; You, Zongbing

    2013-01-01

    When physicians consider which analgesia to use postsurgery, the primary goal is to relieve pain with minimal adverse side effects. Bupivacaine, a commonly used analgesic, has been formulated into an aqueous suspension of multivesicular liposomes that provide long-lasting analgesia for up to 72 hours, while avoiding the adverse side effects of opioids. The increased efficacy of liposomal extended-release bupivacaine, compared to bupivacaine hydrochloride, has promoted its usage in a variety of surgeries including hemorrhoidectomy, bunionectomy, inguinal hernia repair, total knee arthroplasty, and augmentation mammoplasty. However, like other bupivacaine formulations, the liposomal extended-release bupivacaine does have some side effects. In this brief review, we provide an update of the current knowledge in the use of bupivacaine for postsurgical analgesia. PMID:24043932

  18. Trigger release liposome systems: local and remote controlled delivery?

    PubMed

    Bibi, Sagida; Lattmann, E; Mohammed, Afzal R; Perrie, Yvonne

    2012-01-01

    Target-specific delivery has become an integral area of research in order to increase bioavailability and reduce the toxic effects of drugs. As a drug-delivery option, trigger-release liposomes offer sophisticated targeting and greater control-release capabilities. These are broadly divided into two categories; those that utilise the local environment of the target site where there may be an upregulation in certain enzymes or a change in pH and those liposomes that are triggered by an external physical stimulus such as heat, ultrasound or light. These release mechanisms offer a greater degree of control over when and where the drug is released; furthermore, targeting of diseased tissue is enhanced by incorporation of target-specific components such as antibodies. This review aims to show the development of such trigger release liposome systems and the current research in this field.

  19. Liposomes as a potential ocular delivery system of distamycin A.

    PubMed

    Chetoni, Patrizia; Monti, Daniela; Tampucci, Silvia; Matteoli, Barbara; Ceccherini-Nelli, Luca; Subissi, Alessando; Burgalassi, Susi

    2015-08-15

    Liposomes containing Distamycin A (DA) may be clinically useful in the treatment of ocular HSV infections, especially in acyclovir-resistant HSV keratitis. This study evaluated the in vitro and in vivo performance of a topical controlled release liposomal formulation containing DA (DA-Lipo) aimed at reducing the toxicity of the encapsulated active agent and improving drug uptake by ocular tissues. The bioavailability of DA in the tear fluid and the DA uptake into the cornea were increased after instillation of DA-Lipo in rabbits, reaching the DA corneal concentration corresponding to IC50 values against HSV without any sign of transcorneal permeation of drug. DA-Lipo was definitely less cytotoxic then plain DA in rabbit corneal epithelial cells. These results provide new insights into the correlation between the in vitro data and the drug kinetics following ocular applications of liposomal vesicles. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Predicting diffusive transport of cationic liposomes in 3-dimensional tumor spheroids.

    PubMed

    Wientjes, Michael G; Yeung, Bertrand Z; Lu, Ze; Wientjes, M Guillaume; Au, Jessie L S

    2014-10-28

    Nanotechnology is widely used in cancer research. Models that predict nanoparticle transport and delivery in tumors (including subcellular compartments) would be useful tools. This study tested the hypothesis that diffusive transport of cationic liposomes in 3-dimensional (3D) systems can be predicted based on liposome-cell biointerface parameters (binding, uptake, retention) and liposome diffusivity. Liposomes comprising different amounts of cationic and fusogenic lipids (10-30mol% DOTAP or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, 1-20mol% DOPE or 1,2-dioleoyl-3-trimethylammonium-propane, +25 to +44mV zeta potential) were studied. We (a) measured liposome-cell biointerface parameters in monolayer cultures, and (b) calculated effective diffusivity based on liposome size and spheroid composition. The resulting parameters were used to simulate the liposome concentration-depth profiles in 3D spheroids. The simulated results agreed with the experimental results for liposomes comprising 10-30mol% DOTAP and ≤10mol% DOPE, but not for liposomes with higher DOPE content. For the latter, model modifications to account for time-dependent extracellular concentration decrease and liposome size increase did not improve the predictions. The difference among low- and high-DOPE liposomes suggests concentration-dependent DOPE properties in 3D systems that were not captured in monolayers. Taken together, our earlier and present studies indicate the diffusive transport of neutral, anionic and cationic nanoparticles (polystyrene beads and liposomes, 20-135nm diameter, -49 to +44mV) in 3D spheroids, with the exception of liposomes comprising >10mol% DOPE, can be predicted based on the nanoparticle-cell biointerface and nanoparticle diffusivity. Applying the model to low-DOPE liposomes showed that changes in surface charge affected the liposome localization in intratumoral subcompartments within spheroids.

  1. Liposomes coated with thiolated chitosan as drug carriers of curcumin.

    PubMed

    Li, Riwang; Deng, Li; Cai, Zhengwei; Zhang, Shuyun; Wang, Kun; Li, Lihua; Ding, Shan; Zhou, Changren

    2017-11-01

    Liposome is one of a promising delivery system to improve water solubility, stability, and bioavailability of curcumin. But its instability is not favorable for long-circulating treatment, controlled release or conservation. To overcome the disadvantages, thiol derivatised chitosan (CSSH) were synthesized and utilized to coat liposomes. The CSSH coated curcumin liposomes (Cur-Lip-CSSH) had an encapsulation efficiency (EE) of 93.95%, a drug loading (DL) of 7.95%, an average particle size of 406.0nm, and a positive zeta-potential of 36.6mV, which were all higher than that of Cur-Lip. Cur-Lip-CSSH showed slower in vitro release than Cur-Lip at pH5.5 and pH7.4, and the higher retention of curcumin would be remained for the following uptake of cells. The stability of the both liposomes at 4°C was almost the same, but Cur-Lip-CSSH displayed a higher stability at room temperature and higher temperature by DSC characterization. Curcumin can inhibit the growth of cancer cells under certain conditions. MCF-7 cell line was used to study its inhibition and proliferation after treating with curcumin and Cur-Lip-CSSH. Treatment of MCF-7 with curcumin and Cur-Lip-CSSH showed dose and time dependent cytotoxicity, with growth suppression at 200μM, 72h, obviously. These results indicate that the proper coating of liposomes is able to improve the stability of liposomes and the Lip-CSSH can function as potential drug delivery system. Copyright © 2017. Published by Elsevier B.V.

  2. Arrays of lipid bilayers and liposomes on patterned polyelectrolyte templates.

    PubMed

    Kohli, Neeraj; Vaidya, Sachin; Ofoli, Robert Y; Worden, Robert M; Lee, Ilsoon

    2006-09-15

    This paper presents novel methods to produce arrays of lipid bilayers and liposomes on patterned polyelectrolyte multilayers. We created the arrays by exposing patterns of poly(dimethyldiallylammonium chloride) (PDAC), polyethylene glycol (m-dPEG) acid, and poly(allylamine hydrochloride) (PAH) on polyelectrolyte multilayers (PEMs) to liposomes of various compositions. The resulting interfaces were characterized by total internal reflection fluorescence microscopy (TIRFM), fluorescence recovery after pattern photobleaching (FRAPP), quartz crystal microbalance (QCM), and fluorescence microscopy. Liposomes composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dioleoyl-sn-glycero-3-phosphate (monosodium salt) (DOPA) were found to preferentially adsorb on PDAC and PAH surfaces. On the other hand, liposome adsorption on sulfonated poly(styrene) (SPS) surfaces was minimal, due to electrostatic repulsion between the negatively charged liposomes and the SPS-coated surface. Surfaces coated with m-dPEG acid were also found to resist liposome adsorption. We exploited these results to create arrays of lipid bilayers by exposing PDAC, PAH and m-dPEG patterned substrates to DOPA/DOPC vesicles of various compositions. The patterned substrates were created by stamping PDAC (or PAH) on SPS-topped multilayers, and m-dPEG acid on PDAC-topped multilayers, respectively. This technique can be used to produce functional biomimetic interfaces for potential applications in biosensors and biocatalysis, for creating arrays that could be used for high-throughput screening of compounds that interact with cell membranes, and for probing, and possibly controlling, interactions between living cells and synthetic membranes.

  3. Activatable bispecific liposomes bearing fibroblast activation protein directed single chain fragment/Trastuzumab deliver encapsulated cargo into the nuclei of tumor cells and the tumor microenvironment simultaneously.

    PubMed

    Tansi, Felista L; Rüger, Ronny; Böhm, Claudia; Steiniger, Frank; Kontermann, Roland E; Teichgraeber, Ulf K; Fahr, Alfred; Hilger, Ingrid

    2017-05-01

    Molecular targeting plays a significant role in cancer diagnosis and therapy. However, the heterogeneity of tumors is a limiting obstacle for molecular targeting. Consequently, clinically approved drug delivery systems such as liposomes still rely on passive targeting to tumors, which does not address tumor heterogeneity. In this work, we therefore designed and elucidated the potentials of activatable bispecific targeted liposomes for simultaneous detection of fibroblast activation protein (FAP) and the human epidermal growth factor receptor 2 (HER2). The bispecific liposomes were encapsulated with fluorescence-quenched concentrations of the near-infrared fluorescent dye, DY-676-COOH, making them detectable solely post processing within target cells. The liposomes were endowed with a combination of single chain antibody fragments specific for FAP and HER2 respectively, or with the FAP single chain antibody fragment in combination with Trastuzumab, which is specific for HER2. The Trastuzumab based bispecific formulation, termed Bi-FAP/Tras-IL revealed delivery of the encapsulated dye into the nuclei of HER2 expressing cancer cells and caused cell death at significantly higher rates than the free Trastuzumab. Furthermore, fluorescence imaging and live microscopy of tumor models in mice substantiated the delivery of the encapsulated cargo into the nuclei of target tumor cells and tumor stromal fibroblasts. Hence, they convey potentials to address tumor plasticity, to improve targeted cancer therapy and reduce Trastuzumab resistance in the future. This work demonstrates the design of activatable bispecific liposomes aimed to target HER2, a poor prognosis tumor marker in many tumor types, and fibroblast activation protein (FAP), a universal tumor marker overexpressed on tumor fibroblasts and pericytes of almost all solid tumors. Encapsulating liposomes with a quenched concentration of a NIRF dye which only fluoresced after cellular degradation and activation enabled

  4. Size and stability of liposomes: a possible role of hydration and osmotic forces.

    PubMed

    Sabín, J; Prieto, G; Ruso, J M; Hidalgo-Alvarez, R; Sarmiento, F

    2006-08-01

    Dynamic light scattering and electrophoretic mobility measurements have been used to characterize the size, size distribution and zeta potentials (zeta-potentials) of egg yolk phosphatidylcholine (EYPC) liposomes in the presence of monovalent ions ( Na(+) and K(+)). To study the stability of liposomes the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory has been extended by introducing the hydrated radius of the adsorbed ions onto the liposome surfaces. The decrease of liposome size is explained on the basis of the membrane impermeability to some ions which generate osmotic forces, which leads to evacuate water from liposome inside.

  5. Liposomal-Encapsulated Stroma-Free Hemoglobin as a Potential Blood Substitute.

    DTIC Science & Technology

    1980-01-02

    circulating life-time even further. If all liposomes are taken up by RE cells, then when 14C- inulin is administered i.v. encapsulated in liposomes one should...of inulin would result only when liposomes become leaky or decompose before being taken up by cells. If liposomes are not maximally stable, then after...some time any liposome which had not been taken-up by RE cells would have decomposed and the released inulin excreted. We have used these facts to

  6. Liposomal squalenoyl-gemcitabine: formulation, characterization and anticancer activity evaluation.

    PubMed

    Pili, Barbara; Reddy, L Harivardhan; Bourgaux, Claudie; Lepêtre-Mouelhi, Sinda; Desmaële, Didier; Couvreur, Patrick

    2010-08-01

    A new prodrug of gemcitabine, based on the covalent coupling of squalene to gemcitabine (GemSQ), has been designed to enhance the anticancer activity of gemcitabine, a nucleoside analogue active against a wide variety of tumors. In the present study, the feasibility of encapsulating GemSQ into liposomes either PEGylated or non-PEGylated has been investigated. The in vivo anticancer activity of these formulations has been tested on subcutaneous grafted L1210wt leukemia model and compared to that of free gemcitabine. The liposomal GemSQ appears to be a potential delivery system for the effective treatment of tumors.

  7. Liposomal squalenoyl-gemcitabine: formulation, characterization and anticancer activity evaluation

    NASA Astrophysics Data System (ADS)

    Pili, Barbara; ReddyCurrent Address: Sanofi-Aventis, 13 Quai Jules-Guesdes, 94403, Vitry-Sur-Seine, France., L. Harivardhan; Bourgaux, Claudie; Lepêtre-Mouelhi, Sinda; Desmaële, Didier; Couvreur, Patrick

    2010-08-01

    A new prodrug of gemcitabine, based on the covalent coupling of squalene to gemcitabine (GemSQ), has been designed to enhance the anticancer activity of gemcitabine, a nucleoside analogue active against a wide variety of tumors. In the present study, the feasibility of encapsulating GemSQ into liposomes either PEGylated or non-PEGylated has been investigated. The in vivo anticancer activity of these formulations has been tested on subcutaneous grafted L1210wt leukemia model and compared to that of free gemcitabine. The liposomal GemSQ appears to be a potential delivery system for the effective treatment of tumors.

  8. Octadecyl ferulate behavior in 1,2-Dioleoylphosphocholine liposomes

    NASA Astrophysics Data System (ADS)

    Evans, Kervin O.; Compton, David L.; Whitman, Nathan A.; Laszlo, Joseph A.; Appell, Michael; Vermillion, Karl E.; Kim, Sanghoon

    2016-01-01

    Octadecyl ferulate was prepared using solid acid catalyst, monitored using Supercritical Fluid Chromatography and purified to a 42% yield. Differential scanning calorimetry measurements determined octadecyl ferulate to have melting/solidification phase transitions at 67 and 39 °C, respectively. AFM imaging shows that 5-mol% present in a lipid bilayer induced domains to form. Phase behavior measurements confirmed that octadecyl ferulate increased transition temperature of phospholipids. Fluorescence measurements demonstrated that octadecyl ferulate stabilized liposomes against leakage, maintained antioxidant capacity within liposomes, and oriented such that the feruloyl moiety remained in the hydrophilic region of the bilayer. Molecular modeling calculation indicated that antioxidant activity was mostly influenced by interactions within the bilayer.

  9. Potential antitumor activity of novel DODAC/PHO-S liposomes

    PubMed Central

    Luna, Arthur Cássio de Lima; Saraiva, Greice Kelle Viegas; Filho, Otaviano Mendonça Ribeiro; Chierice, Gilberto Orivaldo; Neto, Salvador Claro; Cuccovia, Iolanda Midea; Maria, Durvanei Augusto

    2016-01-01

    In recent studies, we showed that synthetic phosphoethanolamine (PHO-S) has a great potential for inducing cell death in several tumor cell lines without damage to normal cells. However, its cytotoxic effect and selectivity against tumor cells could increase with encapsulation in cationic liposomes, such as dioctadecyldimethylammonium chloride (DODAC), due to electrostatic interactions between these liposomes and tumor cell membranes. Our aim was to use cationic liposomes to deliver PHO-S and to furthermore maximize the therapeutic effect of this compound. DODAC liposomes containing PHO-S (DODAC/PHO-S), at concentrations of 0.3–2.0 mM, prepared by ultrasonication, were analyzed by scanning electron microscopy (SEM) and dynamic light scattering. The cytotoxic effect of DODAC/PHO-S on B16F10 cells, Hepa1c1c7 cells, and human umbilical vein endothelial cells (HUVECs) was assessed by MTT assay. Cell cycle phases of B16F10 cells were analyzed by flow cytometry and the morphological changes by SEM, after treatment. The liposomes were spherical and polydisperse in solution. The liposomes were stable, presenting an average of ∼50% of PHO-S encapsulation, with a small reduction after 40 days. DODAC demonstrated efficient PHO-S delivery, with the lowest values of IC50% (concentration that inhibits 50% of the growth of cells) for tumor cells, compared with PHO-S alone, with an IC50% value of 0.8 mM for B16F10 cells and 0.2 mM for Hepa1c1c7 cells, and without significant effects on endothelial cells. The Hepa1c1c7 cells showed greater sensitivity to the DODAC/PHO-S formulation when compared to B16F10 cells and HUVECs. The use of DODAC/PHO-S on B16F10 cells induced G2/M-phase cell cycle arrest, with the proportion significantly greater than that treated with PHO-S alone. The morphological analysis of B16F10 cells by SEM showed changes such as “bleb” formation, cell detachment, cytoplasmic retraction, and ap