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PubMedDate not supplied

Liposomes as cyclosporin A carriers: the influence of ordering of hydrocarbon chains of phosphatidylglycerol liposomes on the association with and topography of cyclosporin A.

The addition of cholesterol and stearylamine to liposomes prepared from phosphatidylglycerol containing saturated and unsaturated fatty acids was studied to determine the effect on binding of cyclosporin A (CsA). It was found that liposomes containing phosphatidylglycerol-stearylamine-cholesterol in the molar ratio of 7:2.25:2 had the highest capacity to bind CsA (36.7 mol of phospholipid to 1 mol of CsA), while binding of CsA to phosphatidylglycerol liposomes, phosphatidylglycerol-stearylamine liposomes, or phosphatidylglycerolcholesterol liposomes was significantly lower (342.9, 174.4 and 422.3 mol of phospholipid to 1 mol of CsA, respectively). The binding of CsA to all these liposomes was compared with their order parameters, obtained by electron spin resonance spectroscopy using 5-nitroxide stearic acid spin probe. It was found that increased binding of CsA paralleled the increased ordering of hydrocarbon chains achieved by addition of cholesterol to these liposomes. When liposomes were prepared from pure dimyristoylphosphatidylglycerol (DMPG), 30.7 mol of DMPG were required to bind 1 mol of CsA. The topography of CsA in phosphatidylglycerol liposomes was established by using 5-nitroxide stearic acid as a spin probe. In DMPG liposomes, CsA was found in hydrocarbon chains adjacent to the polar head group, while in liposomes prepared from phosphatidylglycerol containing mixed fatty acids, CsA was associated with the polar head group region without penetrating the hydrocarbon chains of phosphatidylglycerol.

Cyclosporine↗
PubMedDate not supplied

Formulation kit for liposomal doxorubicin composed of lyophilized liposomes.

BACKGROUND: Doxorubicin can be loaded into preformed liposome by remote loading. Lyophilization of liposomes results in particle size increase and content leakage. Cryoprotectants have been used to improve the stability of liposomal formulations during lyophilization. Here we have developed a formulation kit for liposomal doxorubicin based on lyophilized liposomes incorporating these cryoprotectants. MATERIALS AND METHODS: Liposomes compared of egg phosphatidylcholine/cholesterol and containing either glucose or sucrose as a cryoprotectant were prepared by polycarbonate membrane extrusion. These were then loaded with doxorubicin by a pH-gradient-based remote loading procedure either before or after lyophilization and reconstitution. The loading efficiency of DOX was evaluated by gel-filtration chromatography. The effect of lyophilization on the stability of liposomal DOX was also evaluated. RESULTS: Cryoprotectants were effective in maintaining liposome size distribution but not drug retention during lyophilization. DOX loading efficiency of the reconstituted liposomes was near quantitative and comparable to that of freshly prepared liposomes. CONCLUSION: Liposomal doxorubicin can be produced and stored as a lyophilized kit that can be reconstituted without significant changes to critical formulation properties.

Antibiotics, Antineoplastic↗
PubMed2005

[Mechanisms of action of transportation of liposomes and chitosan-coated liposomes containing leuprolide across intestine and Caco-2 cell].

AIM: To investigate the mechanisms of action of transportation of liposomes and chitosan-coated liposomes containing leuprolide across rat intestine and Caco-2 cell. METHODS: Everted-gut technique and Caco-2 cell were used to study the transport properties of free leuprolide, liposomes and chitosan-coated liposomes containing leuprolide. Caco-2 cell was used to study the effect of chitosan concentration and the order of addition on the permeation of liposomes. RESULTS: The transport of leuprolide was passive diffusion. Probably because the entrapment by liposomes prevents the transport of leuprolide across the rat intestine and Caco-2 cell, the permeation amount of leuprolide from liposomes was lower than that of the free drug. However, liposomes protected the leuprolide from degradation. Chitosan promoted the transport of leuprolide from liposomes and there was no obvious difference in enhancement effect from the concentration of 0.1% to 0.5%. On the other hand, the incubation of chitosan with liposomes may weak the enhancement effect of chitosan. CONCLUSION: Chitosan-coated liposomes showed both protection and enhancement effect, therefore, they may promote the oral absorption of leuprolide.

Animals↗
PubMed2006

Properties of liposomes coated with hydrophobically modified chitosan in oral liposomal drug delivery.

Chitosan (CS) has been widely used as an adhesive coating polymer for oral liposomal drug delivery systems because of its adhesive properties on mucous layers. The coating mechanism or interaction of chitosan and liposomes or mucin mainly depends on electrostatic forces. Thus, to enhance the adhesive properties of chitosan, a hydrophobically modified chitosan, i.e., dodecylated chitosan (DC), was synthesized. BIACORE results showed that both CS and DC could interact with mucin. Differences in sensorgram patterns between chitosan-mucin and dodecylated chitosan-mucin were observed and tentatively attributed to differences in binding kinetics. The zeta potential of dodecylated chitosan-coated liposomes (DC-Lip) showed positive values in both liposomal formulations, i.e., negatively charged and neutral-charge liposomes. These results indicated that DC could be considered a more suitable polymer for coating neutral-charge liposomes than CS because the hydrophobic side chain of DC inserts itself into the lipid bilayer of liposomes. Moreover, CS seemed to be less effective in the coating of a neutral-charge liposome because of the low positive values of its zeta potential. CS provided solely electrostatic forces when used for coating liposomes while DC provided electrostatic and hydrophobic forces due to the long alkyl chain in its backbone. Confocal Laser Scanning Microscopy (CLSM) images indicated that both chitosan-coated liposomes (CS-Lip) and DC-Lip could adhere to and penetrate through the small intestine of rats after oral administration. The pharmacological results showed that DC-Lip had a greater effect in decreasing blood calcium concentration during the first 12 h compared with CS-Lip. Therefore, it can be concluded that dodecylated chitosan can be useful in designing oral liposomal drug delivery systems.

Administration, Oral↗
PubMed1984

Liposome facilitated xenogeneic approach for studying human colon cancer immunity: carrier and adjuvant effect of liposomes.

Liposomes prepared with human LS174T colon tumour cell membranes induce specific primary xenogeneic immune responses in BALB/c splenocytes in vitro. Characterization of the adjuvant role of these liposomes was accomplished by determining the effect on immune induction of several modifications on the liposomal carrier. The results showed that the carrier effect of liposomes was mediated primarily by tumour antigens exposed on the outer surface. Trypsin treatment of the liposomes eliminated 95% of the surface protein and significantly (P less than 0.05) reduced the ability of liposomes to induce cytotoxic splenocytes. The generation of cytolytic activity with liposomes was dose-dependent, with a 10 micrograms protein threshold and a maximal response at 100 micrograms. 'Rigid' liposomes were shown to be significantly (P less than 0.05) more efficacious than fluid liposomes in inducing cytotoxicity. In addition, the data indicate that the xenogeneic cell-mediated immunity exhibits identical classes of effector cells as found in murine-murine reactions. Lymphocytes bearing the THY-1, Lyt-1 and Lyt-2 surface markers were necessary for immune induction. The role of Lyt-123 subpopulation was suggested by the inability to achieve normal cytolytic levels by reconstitution with Lyt-1 plus Lyt-2 cells. Adherent cells were, as expected, necessary for the generation of primary immunity. Indeed, the interaction of I-A+ adherent cells with liposomes for at least 8 h was required to generate subsequent maximal T cell cytotoxic activity. The phenotype of the cytotoxic effector cell was Thy-1+, Lyt-2+, and I-Ad-. If this were an allo-or syngeneic, and not a xenogeneic system, this study would be of less interest. However, when coupled with the known molecular homologies between murine and human lymphocyte antigens, these results suggest that the concept of cross species major histocompatibility complex (MHC) restriction is tenable. Thus the liposome is not only an effective antigen carrier, but also a functional adjuvant for in vitro induced cell-mediated immunity.

Adjuvants, Immunologic↗
PubMed1982

Further studies on the charge-related alterations of methotrexate transport in Ehrlich ascites tumor cells by ionic liposomes: correlation with liposome-cell association.

Interaction of positively (phosphatidylcholine/stearylamine 5:1) or negatively (phosphatidylcholine/stearic acid 5:1) charged liposomes with Ehrlich ascites tumor cells for 1-5 min increases or decreases, respectively, the bidirectional fluxes of the folic acid analog, methotrexate. These effects on influx and efflux appear to be symmetrical since the liposomes do not change the intracellular level of methotrexate at the steady state. Influx kinetics show that these alterations result from an increase or decrease in the Vmax with no change in the Kinm. These effects appear to be specific for the methotrexate-tetrahydrofolate carrier system since the transport of other compounds which utilize this carrier, aminopterin, 5-methyltetrahydrofolate, and 5-formyltetrahydrofolate, is affected similarly to methotrexate, whereas, the transport of folic acid, a compound similar in structure and charge but not significantly transported by this carrier is unaffected by liposomes. Once cells are exposed to charged liposomes, the effects on methotrexate transport cannot be reversed by washing the cells free of the extracellular liposomes. If, however, cells are exposed to liposomes of one charge, washed and then exposed to liposomes of the opposite charge, methotrexate influx is reversed to control rates. The effects of charged liposomes on methotrexate influx were not abolished by treating the cells with neuraminidase, metabolic inhibitors or lowering the temperature to 4 degrees C. Studies on the uptake of [14C] liposomes show that these effects are not proportional to the total amount of lipid associated with the cell but result from an initial rapid liposome-cell association that is not dependent on temperature or energy metabolism nor related to cell surface charge.

Animals↗
PubMed1986

Fusion of Sendai virus with negatively charged liposomes as studied by pyrene-labelled phospholipid liposomes.

Sendai virus particles fuse with negatively charged liposomes but not with vesicles made of zwitterionic phospholipids. The liposome-virus fusion process was studied by dilution of the concentration-dependent excimer-forming fluorophore 2-pyrenyldodecanoylphosphatidylcholine contained in the liposomes by the viral lipids. The data were analyzed in the framework of a mass action kinetic model. This provided analytical solutions for the final levels of probe dilution and numerical solutions for the kinetics of the overall fusion process, in terms of rate constants for the liposome-virus adhesion, deadhesion and fusion. This analysis led to the following conclusions: At neutral pH and 37 degrees C, only 15% of the virus particles can fuse with the phospholipid vesicles, although all the virions may aggregate with the liposomes. The rate constants for aggregation, fusion and deadhesion are of the orders of magnitude of 10(7) M-1 X s-1, 10(-3) s-1 and 10(-2), s-1, respectively. The fraction of active virus increases with temperature. At acidic pH, both the fraction of 'fusable' virus and the rate of fusion increase markedly. The optimal pH for fusion is 3-4, where most of the virus particles are active. At higher pH values, an increasing fraction of the virus particles become inactive, probably due to ionization of viral glycoproteins, whereas at pH values below 3.0 the fusion is markedly reduced, most likely due to protonation of the negatively charged vesicles. While only 15% of the virions fuse with the liposomes at pH 7.4 and 37 degrees C, all the liposomes lose their content (Amselem, S., Loyter, A. Lichtenberg, D. and Barenholz, Y. (1985) Biochim. Biophys. Acta 820, 1-10). We therefore propose that release of entrapped solutes is due to liposome-virus aggregation, and not to fusion. Both trypsinization and heat inactivation of the virus particles inhibit not only the fusion process but also the release of carboxyfluorescein. This demonstrates the obligatory role of viral membrane proteins in liposome-virus aggregation. Reconstituted vesicles made of the viral lipid and the hemagglutinin/neuraminidase (HN) glycoprotein fuse with negatively charged liposomes similar to the intact virions. This suggests that the fusion of virions with negatively charged vesicles, unlike the fusion of the virus with biological membranes, requires only the HN and not the fusion glycoprotein.

Calcium↗
PubMed1990

Substantial glucose leakage from liposomes on filters and upon molecular-sieve chromatography in determinations of reconstituted glucose-transport activity and liposome volumes.

Transport-protein activities are often determined by procedures that involve isolation of liposomes containing the transported radioactive solute. We determined the activity of the human red cell glucose transporter in liposomes and, by similar procedures, internal volumes of liposomes. For these purposes, we isolated freeze-thawed liposomes loaded with [14C]glucose, either by filtration on cellulose-nitrate and cellulose-acetate filters, or by chromatography on Sephadex. The interaction of liposomes with filters caused substantial leakage of [14C]glucose. About half of the internal [14C]glucose was released on the filters from glucose-transporter liposomes with inhibited transport. Chromatography at high flow rate provided higher and more accurate values than did the filtration procedure. Leakage corrections could be made by use of flow-cell scintillation elution profiles. The ratios between the corrected chromatographic volume values and the filtration values were 1.4-3.0 for liposomes without protein, 2.4-4.0 for glucose-transporter liposomes and 3.6-7.9 for liposomes with several human red cell integral membrane proteins. The D-glucose equilibrium exchange with glucose-transporter liposomes at 50 mM D-glucose was 2.0 nmol D-glucose per microgram transporter per second as determined by use of chromatography at high flow rate. The filtration procedure gave only 0.6 nmol.microgram-1.s-1 due to the [14C]glucose leakage. In our experiments, the chromatographic procedure thus proved superior.

Biological Transport↗
PubMed1989

Prostaglandin and thromboxane in liposomes: suppression of the primary immune response to liposomal antigens.

Liposomes containing lipid A as adjuvant and also containing prostaglandin E2 or thromboxane B2 were examined for the ability to influence induction of humoral immunity against liposomal protein or lipid antigens in rabbits. The protein antigen consisted of cholera toxin that was bound to ganglioside GM1 on the surface of the liposomes. High titers of anti-cholera toxin antibodies were produced and IgM and IgG responses were detected. When the immunizing liposomes contained either prostaglandin E2 or thromboxane B2 as part of the lipid bilayer, the primary immune response, involving both IgM and IgG antibodies, was greatly reduced. The secondary immune response observed after a boosting immunization was not suppressed by liposomal eicosanoids. A similar inhibitory effect on the primary response was observed when liposomal lipid antigens were examined instead of cholera toxin. An inhibitory effect of liposomal prostaglandin E2 on the phagocytic uptake of opsonized liposomes by cultured macrophages was also observed, suggesting that liposomal eicosanoids can have direct local effects on macrophages that might influence the immune response to liposomal antigens.

Animals↗
PubMed1995

Mucosal immunoadjuvant activity of liposomes: induction of systemic IgG and secretory IgA responses in mice by intranasal immunization with an influenza subunit vaccine and coadministered liposomes.

This paper reports on a novel immunoadjuvant activity of liposomes. An influenza subunit preparation, containing the isolated viral surface antigens, was incorporated in a liposomal formulation. Administration of this vaccine to mice via the intranasal (i.n.) route resulted in a stimulated serum IgG response relative to the response to i.n. immunization with the antigen alone. In addition, the liposomal vaccine induced a secretory IgA (sIgA) response in the mucosa of the lungs and nasal cavity. Both serum IgG and sIgA responses persisted up to at least 21 weeks postimmunization. Immune stimulation was observed with negatively charged liposomes consisting of phosphatidylcholine (PC), cholesterol and dicetylphosphate (DCP), but not with zwitterionic liposomes, consisting of PC and cholesterol alone. Remarkably, for stimulation of serum IgG responses and induction of an sIgA response, liposomes could be simply mixed with the antigen. Moreover, i.n. administration of empty liposomes up to 48 h prior to i.n. immunization with the subunit antigen also resulted in immune stimulation, indicating that the liposomes did not exert their adjuvant effect by acting as a carrier for the antigen. The liposomal vaccine conferred protection against infection. It is concluded that liposomes, administered i.n., provide a promising adjuvant system for stimulation of antibody responses in general, and mucosal sIgA responses in particular.

Adjuvants, Immunologic↗
PubMed1985

Intracellular digestion of saturated and unsaturated phospholipid liposomes by mucosal cells. Possible mechanism of transport of liposomally entrapped macromolecules across the isolated vascularly perfused rabbit ileum.

The mechanism of intestinal absorption of liposomally entrapped [14C]inulin and 125I-labelled poly(vinylpyrrolidone) was studied using the isolated rabbit intestinal loop with intact perfused vasculature, a system more closely resembling an in vivo system than the everted sac technique. [14C]Inulin or 125I-poly(vinylpyrrolidone) was entrapped in liposomes prepared from unsaturated egg phosphatidylcholine and soya phosphatidylcholine, and saturated distearoylphosphatidylcholine (18:0), dipalmitoylphosphatidylcholine (16:0) and dimyrostoylphosphatidylcholine (14:0). Free and liposomally entrapped macromolecules were introduced in the ileum and the transport of liposomes and entrapped macromolecules into the venous effluent was monitored by measuring the presence of the aqueous marker 125I-poly(vinylpyrrolidone) or [14C]inulin, and lipid marker [3H]cholesterol. The results show that intact liposomes are not transported across intestine into the venous effluent, but they are taken up by mucosal cells and digested intracellularly, releasing the entrapped markers 125I-poly(vinylpyrrolidone) and [14C]inulin. These markers are then transported into the venous effluent as free molecules. The absorption of liposomally entrapped [14C]inulin into the venous effluent is biphasic, first slow for 30 min (i.e., a lag period of 30 min), followed by a rapid linear increase. The duration of the lag period and the rate of absorption of the entrapped [14C]inulin are dependent on the degree of saturation and the transition temperature of the phospholipids used to prepare liposomes. The possible explanation of the lag period based on the evidence presented here is that it is the time required for the liposomes to be taken up by mucosal cells and digested intracellularly. Intracellular digestion of liposomes prepared from saturated phospholipids is more rapid than from those prepared from unsaturated phospholipids, and the greater the fatty acid chain length of the saturated phospholipids the more rapid the intracellular degradation of liposomes.

Animals↗
PubMed2006

Pharmacokinetics of poly(hydroxyethyl-l-asparagine)-coated liposomes is superior over that of PEG-coated liposomes at low lipid dose and upon repeated administration.

'Stealth' liposomes with a poly(ethylene glycol) (PEG) coating are frequently studied for drug delivery and diagnostic purposes because of their prolonged blood circulation kinetics. However, several recent reports have demonstrated that PEG-liposomes are rapidly cleared at single low lipid doses (<1 micromol/kg) and upon repeated administration (time interval between the injections 5 days-4 weeks). Recently, poly(amino acid)-based stealth liposome coatings have been developed as alternative to the PEG-coating. In this study, the pharmacokinetic behavior of liposomes coated with the poly(amino acid) poly(hydroxyethyl-l-asparagine) (PHEA) was evaluated at low lipid doses and upon repeated administration in rats. Blood circulation times and hepatosplenic localization of PHEA-liposomes were assessed after intravenous injection. When administered at a dose of 0.25 micromol/kg or less, PHEA-liposomes showed significantly longer blood circulation times than PEG-liposomes. A second dose of PHEA-liposomes 1 week after the first injection was less rapidly cleared from the circulation than a second dose of PEG-liposomes. Although the mechanisms behind these observations are still not clear yet, the use of PHEA-liposomes appears beneficial when single low lipid doses and/or repeated dosing schedules are being applied.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2006

Liposomal drugs dispersed in hydrogels. Effect of liposome, drug and gel properties on drug release kinetics.

Release of calcein and griseofulvin (GRF) from control (gels in which solutes are dissolved in) and liposomal gels was studied using agarose-assisted immobilization as a technique to separate gels from drug-receptor compartments. Liposomes composed of phosphatidylcholine (PC) or distearoyl-glycero-PC and cholesterol (DSPC/Chol), and incorporating calcein or GRF were prepared by thin film hydration. After cleaning the liposomes they were dispersed in different hydrogels (carbopol 974 [1, 1.5 or 2% (w/w)], hydroxylethyl-cellulose (HEC) [4% (w/w)], or a mixture of the two), and release of calcein or GRF was followed by fluorescence or photometric technique, respectively. Results show that calcein release from liposomal gels is slower compared to control gels, and can be further retarded by using rigid-membrane liposomes (faster release from PC-liposome compared to DSPC/Chol-liposome gels). Additionally, calcein release is not affected by the lipid amount loaded (in the range from 2 to 8 mg/ml), therefore solute loading can be controlled according to needs. Oppositely, GRF release from liposomal gels is determined by drug loading. At high drug loading levels (compared to GRF aqueous solubility), GRF is released with constant rate from liposomal gels irrespective of liposome type (PC or DSPC/Chol). Thereby, for amphiphilic/lipophilic drugs, drug properties (solubility, log P) determine the system behavior. Calcein and GRF release from control carbopol gels is faster compared to HEC and mixture gels. The same is true for calcein in liposomal gels. Carbopol gel rheological properties were found to be significantly different (compared to the other gels), implying that these characteristics are important for drug diffusion from gels.

Drug Carriers↗
PubMed2006

Immobilization of liposomes onto quartz crystal microbalance to detect interaction between liposomes and proteins.

To study the interaction between liposomes and proteins, intact liposomes were immobilized on a metal planar support by chemical binding and/or bioaffinity using a quartz crystal microbalance (QCM). A large decrease in the resonance frequency of quartz crystal was observed when the QCM, modified by a self-assembled monolayer (SAM) of carboxythiol, was added to liposome solutions. The stable chemical immobilization of intact liposomes onto SAM was judged according to the degree with which adsorbed mass depended on the prepared size of liposomes, as well as on the activation time of SAMs when amino-coupling was introduced, where the liposome coverage of electrodes was 69+/-8% in optimal conditions. When avidin-biotin binding was used on amino-coupling liposome layers, liposome immobilization finally reached 168% coverage of the electrode surface. Denatured protein was also successfully detected according to the change in the frequency of the liposome-immobilized QCM. The adsorbed mass of denatured carbonic anhydrase from bovine onto immobilized liposomes showed a characteristic peak at a concentration of guanidine hydrochloride that corresponded to a molten globule-like state of the protein, although the mass adsorbed onto deactivated SAM increased monotonously.

Adsorption↗
PubMed2001

Conjugation of anti-My9 antibody to stealth monensin liposomes and the effect of conjugated liposomes on the cytotoxicity of immunotoxin.

The carboxylic ionophore, monensin, was successfully entrapped in stealth liposomes by employing the pH-gradient method (interior pH of liposomes 9.5; exterior pH 5.0-5.9). A maximum of 14% of monensin could be entrapped in stealth liposomes by this method. The stealth liposomes could be successfully freeze-dried having mean particle size varying between 197 and 223 nm. The stealth liposomes were conjugated to anti-My9 monoclonal antibody (targeted against CD 33 antigen) by a disulfide linkage with almost full retention of immunoreactivity. The method of conjugation of liposomes with the antibody did not alter the particle size of liposomes and resulted in only 10% leakage of monensin. In-vitro cytotoxicity studies showed that antibody-conjugated monensin liposomes (3.5x10(-8) M monensin) potentiated the cytotoxicity of anti-My9 immunotoxin by a factor of 2070, in comparison to 360-fold potentiation observed with unconjugated monensin liposomes against human HL-60 promyelocytic leukemia cells. These results indicate that it is possible to enhance the in-vitro cytotoxicity of immunotoxin by several folds using antibody-conjugated monensin liposomes.

Antibodies, Monoclonal↗
PubMed2002

Modulation of murine liver macrophage clearance of liposomes by diethylstilbestrol. The effect of vesicle surface charge and a role for the complement receptor Mac-1 (CD11b/CD18) of newly recruited macrophages in liposome recognition.

We have studied the blood clearance and reticuloendothelial organ distribution of intravenously injected neutral (egg phosphatidylcholine, egg PC/cholesterol, mol ratio 7:2), anionic (egg PC/cholesterol/dicetylphosphate, mol ratio 7:2:1), and cationic (egg PC/cholesterol/stearylamine, mol ratio 7:2:1) liposomes of approximately the same size distribution in mice 3 days after treatment with the synthetic oestrogen diethylstilbestrol (DES). Male mice administered DES intraperitoneally at a dose of 1 mg per mouse (body weight 22-25 g) manifested an increase in the vascular clearance rate of liposomes irrespective of the initial vesicle surface charge. The enhancement in the vascular clearance of liposomes in DES-treated animals was associated with a concomitant increase in liver weight as well as hepatic phagocytosis. However, DES treatment significantly enhanced the hepatic sequestration (on the basis of % of injected dose of liposomes per g of liver tissue) of positively charged liposomes when compared to both neutral and negatively charged vesicles of similar size distribution. This observation was also confirmed by the 'hepatic-blockade' experiments where blockade was induced by prior intravenous injection of liposomes of the same size distribution and charge to that of test vesicles. The in vitro cell suspension studies suggested that the enhanced liposome uptake (irrespective of the initial vesicle surface charge) by Kupffer cells of DES-treated mice was independent of changes in the blood opsonization processes. Furthermore, in vitro studies also showed the operation of multiple mechanisms and involvement of different populations of liver macrophages (resident and recruited cells) in liposome recognition following DES treatment. For example, in DES-treated animals, the newly recruited liver macrophages were found to play a major role in the clearance of stearylamine incorporated liposomes via complement receptors (Mac-1). The resident Kupffer cells seem to recognize cationic vesicles via other receptors as the expression of Mac-1 is virtually absent in these cells. On the other hand, complement receptors seem to play a minor role in the uptake of anionic DCP vesicles by hepatic macrophages of DES-treated mice. DES appears to offer a new approach in dissecting the mechanisms of liposome-macrophage interaction.

Animals↗
PubMed1997

Lung specific stealth liposomes: stability, biodistribution and toxicity of liposomal antitubercular drugs in mice.

Liposomes with enhanced affinity towards lung tissue were prepared for the development of more effective chemotherapy against tuberculosis. Modification of surface of stealth liposomes by tagging O-stearylamylopectin (O-SAP) resulted in the increased affinity of these liposomes towards lung tissue of mice. Liposomes containing egg phosphatidylcholine (ePC), cholesterol (CH), dicetylphosphate (DCP), O-SAP and monosialogangliosides (GM1)/distearylphosphatidylethanolamine-poly(ethylene glycol) 2000 (DSPE-PEG 2000) were found to be most stable in serum. Tissue distribution of these liposomes showed more accumulation in lungs than in reticuloendothelial systems (RES) of normal and tuberculous mice. Pre administration of PC and CH (2:1.5) liposomes before the injection of lung specific stealth liposomes further enhanced their uptake in lungs. In vivo stability of these liposomes demonstrated the slow and controlled release of their encapsulated contents. Isoniazid and rifampicin encapsulated in liposomes were less toxic to peritoneal macrophages as compared to free drugs. Further, encapsulated drugs also demonstrated reduced in vivo toxicity in comparison to free drug(s). These findings suggest liposomes to be better drug delivery vehicles for experimental tuberculosis.

Alanine Transaminase↗
PubMed2002

HEPC-based liposomes trigger cytokine release from peripheral blood cells: effects of liposomal size, dose and lipid composition.

The immune response caused by liposome stimulation was studied by assessing the level of several cytokines released from human peripheral blood cells. Liposome stimulation resulted in the release of IL-6, IL-10, IL-1beta, TNF-alpha and IFN-gamma. The size of the liposomes affected the degree of the cytokine releases with larger sized liposomes causing higher levels of cytokine induction. In addition, it appears that the lipid composition of liposomes had no effect on the degree of cytokine release. The release of cytokines occurred even in the absence of serum, suggesting that serum proteins did not contribute to liposome stimulation in peripheral blood cells. The release of cytokines induced by liposome stimulation was inhibited by the presence of either protein kinase-C (PKC) or protein tyrosine kinase (PTK) inhibitor, but not by the presence of an endocytosis inhibitor. This indicates that signal transduction via PKC or PTK is necessary, in order for human peripheral blood cells to release cytokines (IL-6, IL-10, IL-1beta, TNF-alpha and IFN-gamma) as the result of liposome stimulation. These quantitative data on the release of cytokines by liposomal stimulation provide useful information for the development of rational drug delivery systems and the safety of cytokine induction via the use of liposomes.

Cytokines↗