Sustained release of cisplatin from multivesicular liposomes: potentiation of antitumor efficacy against S180 murine carcinoma

Cisplatin was encapsulated into multivesicular liposomes (MVLs) and the entrapment efficiency, size distribution, and in vitro drug release characteristics of the cisplatin-MVLs were studied. Pharmacokinetics, tissue distribution, and therapeutic efficacy of cisplatin-MVLs were compared against injection of cisplatin solution into mice inoculated with the murine carcinoma 180 (S180) tumor. The results showed that the cisplatin-MVLs were capable of high drug loading (0.148:1 mg cisplatin/mg lipid) and high encapsulation efficiency (>80%). The mean diameter of cisplatin-MVLs was 17 microm. In vitro studies of cisplatin-MVLs in saline solution showed that they sustained release of encapsulated drug for >7 days. Cisplatin-MVLs showed higher drug accumulation in the liver, spleen, and tumor regions than cisplatin solution, as well as higher plasma concentrations and a longer circulation time. The therapeutic efficacy of the cisplatin-MVL preparation against S180 tumor-bearing mice is significantly higher than that of cisplatin solution.     

Encapsulation and stability of clofazimine liposomes.

The entrapment of clofazimine (CLO) in a liposomal delivery system for topical application can protect it from absorption into the blood circulation and increase its residence time within the skin. This may reduce the very long mean period of leprosy treatment, as well as the side effects due to the long term administration of large doses of the drug. This investigation deals with critical parameters controlling the formulation and stabilization of liposomes with encapsulated CLO. The entrapment efficiency of CLO in liposomes was increased by altering the proportion of phosphatidyl choline (PC) and cholesterol (CHOL) in liposomes. The stability of liposomal suspensions and the liposomal gels (HPMC K4M) in terms of retention of CLO was measured at refrigeration temperature (2-8 degrees C), room temperature (25 +/- 2 degrees C) and body temperature (37 degrees C) for a period of 3 months. The results show that entrapment of CLO in liposomes can be increased by increasing the proportion of PC. However, the optimum encapsulation and retention of CLO was achieved only with a specific PC:CHOL molar ratio (5.13:1.00). An almost identical value of the entrapment efficiency was obtained when gel filtration and ultracentrifugation methods were used to separate the CLO-carrying liposomes from free drug. The effect of vortexing and sonication on the entrapment efficiency gave similar results, although the mean particle size was different. CLO liposomal gels were found to be stable at room temperature for up to 3 months.     

Development and characterization of dutasteride bearing liposomal systems for topical use

Dutasteride loaded liposomal system were developed for topical application in order to avoid the side effects associated with the oral administration of the drug. Drug-loaded multilamellar liposomes were prepared using thin-film hydration method followed by sonication and optimized with respect to entrapment efficiency, drug payload, size and lamellarity. The vesicular systems consisting of egg phosphatidylcholine (100 mg), cholesterol (50 mg), and dutasteride (5 mg) showed highest drug entrapment efficiency (94.6%) and drug payload (31.5 μg/mg of total lipids). Mean vesicle size of these liposomes was noted to be 1.82 ± 0.15 μm. Significantly higher skin permeation of dutasteride through excised abdominal mouse skin was achieved via the developed liposomal formulations as compared to hydro-alcoholic solution and conventional gels. The formulation exhibited about seven fold higher deposition of drug in skin. Stability studies indicated that the liposomal formulations were quite stable in the refrigerated conditions for 10 weeks with negligible drug leakage or vesicle size alteration. Results of the current studies exhibited improved and localized drug action in the skin and thus could be formulated as a better option to cure androgenetic alopecia.     

Effect of formulation design and freeze-drying on properties of fluconazole multilamellar liposomes

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.     

Formulation of Liposome for topical delivery of arbutin

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.     

Increasing bioavailability of silymarin using a buccal liposomal delivery system: preparation and experimental design investigation

Silymarin is a natural lipotropic agent of low bioavailability from oral products. The aim of our study is to prepare buccal liposomal delivery system of silymarin with higher bioavailability. The effect of lecithin:cholesterol molar ratio on the percentage drug encapsulated was investigated. The influence of fluctuating the amount of added drug was also determined. The effect of additives such as positive charge inducer, negative charge inducer and surfactants was studied using two different 2(3) full factorial designs. Furthermore, additives used to optimize liposomal product were also investigated for their optimal concentrations, release properties and in vitro permeation and absorption through chicken cheek pouch. Optimal liposomal encapsulation efficiency was found at 7:4 lecithin to cholesterol molar ratio. A decrease in entrapment efficiency with increasing cholesterol content was observed. Tween 20 or Tween 80 beyond 0.5 molar ratio decreased the entrapment efficiency. Positively charged liposomes showed superior entrapment efficiency over neutral and negatively charged liposomes. Release studies as well as permeation and absorption studies showed that hybrid liposomes prepared according to formula 3 containing lecithin, cholesterol, stearyl amine and Tween 20 in 9:1:1:0.5 molar ratio, respectively, gave the best drug absorption and permeation. It showed steady state permeation through chicken cheek pouch for 6h. This is expected to improve the bioavailability of silymarin in the developed liposomal buccal delivery system, as the results show an increase in drug penetration compared to free drug powder.     

Enhanced transdermal delivery of acyclovir sodium via elastic liposomes

The elastic liposomes bearing acyclovir sodium were prepared for its enhanced transdermal delivery by conventional rotary evaporation method and characterized for various parameters such as vesicle shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, polydispersity index, turbidity and in vitro release pattern. Permeability studies of acyclovir sodium incorporated in elastic liposomes were performed across artificial membranes and rat skin. Skin permeation potential of the developed formulation was assessed using confocal laser scanning microscopy, that revealed an enhanced permeation of the formulation to the deeper layers of the skin (up to 160 microm) following channel like pathways. Skin permeation profile of elastic liposomal formulation bearing acyclovir sodium was observed and the investigations revealed an enhanced transdermal flux (6.21 +/- 1.8 microg/cm(2)/hr) and decreased lag time (0.6 hr) for acyclovir sodium. The obtained flux was nearly 2.0 and 6.3 times higher than conventional liposomal formulation bearing acyclovir sodium and plain drug solution, respectively (p < 0.01). The elastic liposomal formulation for transdermal delivery of acyclovir sodium provides better transdermal flux, higher entrapment efficiency, ability as a self-penetration enhancer and effectiveness for transdermal delivery as compared with conventional liposomes. In vivo studies showed that on transdermal application of elastic liposomes, the concentration of acyclovir sodium in plasma was found to be 105 +/- 9.4 ng/ml after 24 hr which is about 4.2 times compared with conventional liposomes. Thus it is concluded that the elastic liposomes may be promising vehicles for the transdermal delivery of acyclovir sodium.     

Elastic liposomes mediated transdermal delivery of an anti-hypertensive agent: propranolol hydrochloride

One major problem encountered in transdermal drug delivery is the low permeability of drugs through the skin barrier. In the present investigation ultradeformable lipid vesicles, that is, elastic liposomes were prepared incorporating propranolol hydrochloride for enhanced transdermal delivery. Elastic liposomes bearing propranolol hydrochloride were prepared by conventional rotary evaporation method and characterized for various parameters including vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, turbidity, and in vitro drug release. In vitro flux, enhancement ratio (ER), and release pattern of propranolol hydrochloride were calculated for transdermal delivery. In vivo study conducted on male albino rats (Sprague Dawley) was also taken as a measure of performance of elastic liposomal, liposomal, and plain drug solution. The better permeation through the skin was confirmed by confocal laser scanning microscopy (CLSM). Results indicate that the elastic liposomal formulation for transdermal delivery of propranolol hydrochloride provides better transdermal flux, higher entrapment efficiency, ability as a self-penetration enhancer and effectiveness for transdermal delivery as compared to liposomes.     

Development of liposomal systems of finasteride for topical applications: design, characterization, and in vitro evaluation

Finasteride (FNS) is a "drug of choice" for benign prostate hypertrophy and prostate cancer. The drug has also been reported to be useful orally in the treatment of some difficult-to-treat androgen-dependent skin disorders, such as seborrhea, acne, hirsutism, and androgenetic alopecia. However, the ideal route for its administration (i.e., topical) remains unexplored. This has logically suggested the search for strategic formulation approaches to make the drug effective on topical applications, hitherto unexplored. The present study targets the encasement of drug molecules in the interiors of vesicular compartments (liposomes) made up of hydrogenated phospholipids, as an attempt toward the development of a trans-epidermal therapeutic system of FNS. Multilamellar drug-loaded liposomes were prepared by thin-film hydration with sonication method and optimized with respect to drug payload, entrapment efficiency, and size by formulating different vesicular compositions under different process conditions. The vesicular systems consisting of saturated phospholipid (100 mg), cholesterol (50 mg), and FNS (5 mg) showed highest drug payload (2.9 mg/100 mg of total lipids), and drug entrapment efficiency (88.6%). Mean (+/-SD) vesicle size of the prepared liposomes was found to be 3.66+/-1.6 microm. Significantly higher skin permeation of FNS through excised abdominal mice skin of FNS was achieved from the liposomal formulations vis-à-vis corresponding solution and conventional gels. Liposomal FNS formulations also showed more than fivefold higher deposition of drug in skin than the corresponding plain drug solution and conventional gel. Stability studies indicated that the liposomal formulations were quite stable in the refrigerated conditions for 2 months with negligible drug leakage or vesicle size alteration during the storage period. Results of the current studies with FNS-loaded vesicular systems project the high plausibility of a topical liposomal formulation for effective localized delivery of Finasteride.     

Development of Liposomal Systems of Finasteride for Topical Applications: Design,Characterization, and In Vitro Evaluation

Finasteride (FNS) is a “drug of choice” for benign prostate hypertrophy and prostate cancer. The drug has also been reported to be useful orally in the treatment of some difficult-to-treat androgen-dependent skin disorders, such as seborrhea, acne, hirsutism, and androgenetic alopecia. However, the ideal route for its administration (i.e., topical) remains unexplored. This has logically suggested the search for strategic formulation approaches to make the drug effective on topical applications, hitherto unexplored. The present study targets the encasement of drug molecules in the interiors of vesicular compartments (liposomes) made up of hydrogenated phospholipids, as an attempt toward the development of a trans-epidermal therapeutic system of FNS. Multilamellar drug-loaded liposomes were prepared by thin-film hydration with sonication method and optimized with respect to drug payload, entrapment efficiency, and size by formulating different vesicular compositions under different process conditions. The vesicular systems consisting of saturated phospholipid (100 mg), cholesterol (50 mg), and FNS (5 mg) showed highest drug payload (2.9 mg/100 mg of total lipids), and drug entrapment efficiency (88.6%). Mean (± SD) vesicle size of the prepared liposomes was found to be 3.66 ± 1.6 μm. Significantly higher skin permeation of FNS through excised abdominal mice skin of FNS was achieved from the liposomal formulations vis-à-vis corresponding solution and conventional gels. Liposomal FNS formulations also showed more than fivefold higher deposition of drug in skin than the corresponding plain drug solution and conventional gel. Stability studies indicated that the liposomal formulations were quite stable in the refrigerated conditions for 2 months with negligible drug leakage or vesicle size alteration during the storage period. Results of the current studies with FNS-loaded vesicular systems project the high plausibility of a topical liposomal formulation for effective localized delivery of Finasteride.     

Preparation and evaluation of a liposomal formulation of sodium cromoglicate

Sodium cromoglicate (SCG) is given by inhalation in prophylactic control of asthma. It was encapsulated in liposomes with a view to improve utilization of the drug when given via pulmonary route. The liposomes were characterized for encapsulation efficiency, shape, size and release rate. Liposomal dispersions were freeze-dried using a cryoprotectant. Freeze-dried liposomal dispersion retained 60% of drug upon reconstitution but increase in size of liposomes was noted. Liposomes exhibited good keeping properties when stored at 4 degrees C. In vivo performance of liposomal SCG was evaluated in sensitized guinea pigs. In one of the studies, differential leukocyte count and total leukocyte count in bronchoalveolar lavage fluid was measured. Liposomal dispersion showed significant inhibition of influx of neutrophils as compared with drug solution at 24 h. However, in the second study, when recovery period required by animal to revert back to normal respiratory pattern from the onset or preconvulsion time was measured, no significant difference was found between drug solution and liposomal dispersion when administered 2 h before allergen challenge.     

Formulation of plumbagin loaded long circulating pegylated liposomes: in vivo evaluation in C57BL/6J mice bearing B16F1 melanoma

Context and Objective: Plumbagin (2-methyl, 5-hydroxy, 1, 4-naphthoquinone), an anticancer agent is encapsulated either as conventional or long circulating liposomal formulations to enhance its biological half-life and antitumor efficacy.

Methods: The liposomes were prepared by thin film hydration method and in vitro characterization was carried out to examine the particle size, zeta potential, drug encapsulation efficiency and in vitro release. The optimized formulations were tested for pharmacokinetic and pharmacodynamic efficacy against mice bearing B16F1 melanoma. Also in vivo toxicity studies were carried out.

Results and Discussion: The optimum particle size and entrapment efficiency was observed at drug to lipid molar ratio of 1:20. The in-vitro release of plumbagin from the liposomal formulations in phosphate-buffered saline (pH 7.4) showed biphasic release with an initial burst release followed by sustained release phase. Elimination half life (T_1/2) of pegylated, conventional and free plumbagin was 1305.76?±?278.16, 346.87?±?33.82 and 35.89?±?7.95?min respectively. Further, plumbagin exhibited better antitumor efficacy in vivo when administered as long circulating liposomes with no signs of normal tissue toxicity.

Conclusion: It can be concluded that the pegylated liposomes could provide a promising parenteral platform for plumbagin with enhanced plasma half-life and therapeutic efficacy.     

Proliposomes of indomethacin for oral administration

Indomethacin, a non-steroidal anti-inflammatory drug was encapsulated into liposomes composed of soyabean lecithin, cholesterol and stearylamine for oral administration. Liposomes of homogenous size distribution and higher entrapment efficiency were derived from effervescent granule based proliposomes. The efficacy of the oral route was studied by measuring ulcerogenic index and anti-inflammatory activity using carrageenan induced paw oedema test in rats. The effervescent granule based liposomal products exhibited improved in vivo performance with reference to their cytoprotective and anti-inflammatory activities.     

Characterization of a liposome-based formulation of oxaliplatin using capillary electrophoresis: Encapsulation and leakage

A capillary electrophoresis-based method to characterize a PEGylated liposomal drug formulation of the anti-cancer agent oxaliplatin was developed. Pharmaceutical characterization in terms of determination of the free and total oxaliplatin concentrations in the liposomal formulation was successfully performed allowing calculation of the percentage of encapsulated drug and encapsulation efficiency. The trapping efficiency was likewise calculated. The capillary electrophoresis method allowed liposome characterization in the intended formulation media (sucrose solution with low electrolyte concentration), and the attained results were consistent with inductively coupled plasma mass spectrometry measurements. Accelerated drug leakage studies were initiated by the sonication of the PEGylated formulation, using an ultrasound probe, subsequently the drug leakage was determined by capillary electrophoresis. The results obtained with the PEGylated liposomes demonstrate that capillary electrophoresis may be a useful tool for the characterization of liposomal drug formulations.     

Development and evaluation of inhalational liposomal system of budesonide for better management of asthma

Budesonide is a corticosteroid used by inhalation in the prophylactic management of asthma. However, frequent dosing and adverse effects (local and systemic) remain a major concern in the use of budesonide. Liposomal systems for sustained pulmonary drug delivery have been particularly attractive because of their compatibility with lung surfactant components. In the present investigation, pulmonary liposomal delivery system of budesonide was prepared by film hydration method and evaluated for sustained release. Various parameters were optimized with respect to entrapment efficiency as well as particle size of budesonide liposomes. For better shelf life of budesonide liposomes, they were freeze dried using trehalose as cryoprotectant. The liposomes were characterized for entrapment efficiency, particle size, and surface topography; in vitro drug release was evaluated out in simulated lung fluid at 37° at pH 7.4. The respirable or fine particle fraction was determined by using twin stage impinger. The stability study of freeze dried as well as aqueous liposomal systems was carried out at 2-8° and at ambient temperature (28±40). The freeze dried liposomes showed better fine particle fraction and drug content over the period of six months at ambient as well as at 2-8° storage condition compared to aqueous dispersion of liposomes.     

Electrosteric stealth Rivastigmine loaded liposomes for brain targeting: preparation,characterization, ex vivo,bio-distribution and in vivo pharmacokinetic studies

Being one of the highly effective drugs in treatment of Alzheimer’s disease, Rivastigmine brain targeting is highly demandable, therefore liposomal dispersion of Rivastigmine was prepared containing 2?mol% PEG-DSPE added to Lecithin, Didecyldimethyl ammonium bromide (DDAB), Tween 80 in 1:0.02:0.25 molar ratio. A major challenge during the preparation of liposomes is maintaining a stable formulation, therefore the aim of our study was to increase liposomal stability by addition of DDAB to give an electrostatic stability and PEG-DSPE to increase stability by steric hindrance, yielding what we called an electrosteric stealth (ESS) liposomes. A medium nano-sized liposome (478?±?4.94?nm) with a nearly neutral zeta potential (ZP, ?8?±?0.2?mV) and an entrapment efficiency percentage of 48?±?6.22 was prepared. Stability studies showed no major alteration after three months storage period concerning particle size, polydispersity index, ZP, entrapment efficiency and in vitro release study confirming the successful formation of a stable liposomes. No histopathological alteration was recorded for ESS liposomes of the sheep nasal mucosa. While ESS liposomes showed higher % of drug permeating through the sheep nasal mucosa (48.6%) than the drug solution (28.7%). On completing the in vivo pharmacokinetic studies of 36 rabbits showed 424.2% relative bioavailability of the mean plasma levels of the formula ESS compared to that of RHT intranasal solution and 486% relative bioavailability of the mean brain levels.     

Arsenic trioxide encapsulated liposomes prepared via copper acetate gradient loading method and its antitumor efficiency

In this study, arsenic trioxide (ATO) was encapsulated in liposomes via copper acetate (Cu(OAc)₂) gradients and high entrapment efficiency of over 80% was obtained. The average particle size and the zeta-potential of the liposomes were detected to be 115.1 ± 29.1 nm and −21.97 ± 0.6 mV, respectively. The TEM images showed rod-like precipitates in the inner aqueous phase, which was supposed be due to the formation of insoluble ATOCu complex. The in vitro drug release of ATOCu liposomes exhibited a sustained release over 72 h, and the release rates decreased with the increase of the pH of release media. Pharmacokinetic and tissue distribution studies of ATO liposomes showed significantly reduced plasma clearance rate, increased AUC_0–12h and T_1/2, and improved tumor distribution of As compared to iv administration of ATO solution. The anti-tumor effect of ATO loaded liposomes to S180 tumor-bearing mice was significantly improved with a tumor inhibition rate of 61.2%, meanwhile the toxicity of encapsulated ATO was greatly decreased. In conclusion, ATO can be effectively encapsulated into liposomes by remote loading method via Cu(OAc)₂ gradients; the co-administration of ATO and Cu(II) via liposomal formulation may find wide applications in the treatment of various tumors.     

Effect of preparation technique on the properties of liposomes encapsulating ketoprofen-cyclodextrin complexes aimed for transdermal delivery

The combined approach of cyclodextrin complexation and entrapment in liposomes was investigated in order to develop an effective topical formulation of ketoprofen. Equimolar complex of drug and hydroxypropyl-beta-cyclodextrin (HPbetaCyd) was added at different concentrations to the aqueous phase of liposomes consisting of phosphatidylcholine and cholesterol (60%/40%, w/w). Liposomes were prepared with different techniques, such as thin layer evaporation, freezing and thawing, extrusion through microporous membrane, and reverse phase evaporation method, obtaining, respectively, multi-lamellar vesicles (MLV), frozen and thawed MLV (FATMLV), small uni-lamellar vesicles (SUV) and large uni-lamellar vesicles (LUV). Size and morphology of the different types of liposomes were investigated by light scattering analysis, transmission electron microscopy, and confocal laser scanning microscopy, whereas drug entrapment efficiency was determined by dialysis experiments. Cyclodextrin complexation improved drug solubilization and allowed a strong improvement of its entrapment into the aqueous liposomal phase. Liposome preparation method and operating conditions clearly affected both liposome size and drug loading capacity. Encapsulation efficiency increased with increasing the complex concentration up to 10 mM, and was in the order MLV>LUV>SUV. An opposite behaviour was observed for FATMLV, probably due to the freezing phase required by such a preparation method, which reduced the complex solubility. Moreover, it was not possible to use higher complex concentrations, due to the destabilizing effect of cyclodextrins toward the liposomal membrane. Permeability studies of drug-HPbetaCyd complexes, directly in solution or incorporated in liposomes, performed across artificial membranes simulating the skin behaviour, highlighted, as expected, a prolonged release effect of liposomal formulations. Furthermore, the drug permeation rate depended on the vesicle characteristics and varied in the order: SUV>MLV=FATMLV>LUV. Therefore, the most suitable liposome preparation method can be suitably selected on the basis of drug encapsulation efficiency and/or desired drug release rate.     

Effect of various formulation variables on the encapsulation and stability of dibucaine base in multilamellar vesicles

Formulation of local anesthetics in liposomal topical drug delivery system could provide a sustained and localized anesthesia. The aim of this study was to develop a liposomal dibucaine base (DB) local anesthetic delivery system. DB-loaded multilamellar vesicles (MLVs) were prepared through varying lipid composition, induced charge and pH of the hydration medium. Liposomes were characterized for morphology, size, entrapment efficiency (EE), in vitro drug release and stability including leakage stability. The percentage of drug entrapped in liposomes was found to be hydration medium pH dependent and charge dependent and more pronounced for negatively charged liposomes prepared using hydration medium of pH 9. In vitro release studies of liposomes have shown a sustained release of entrapped dibucaine compared to control solution. Results revealed that adjusting the various formulation variables of dibucaine base MLVs could yield stable and effective topical liposomal local anesthetic formulations.     

Preparation and pharmacological evaluation of silibinin liposomes

The aim of the present study was to encage a drug into liposomal structures to make them more effective, safe and targeted to liver cells. The investigation deals with critical parameters controlling the formulation and evaluation of silibinin (silymarin, CAS22888-70-6) liposomes. Small unilamellar liposmal vesicles were prepared using the ethanol injection method. The various formulation and process variables were optimized to improve the drug entrapment efficiency. The study includes the selection of lipid composition, impact of charge imparting agent and the nature of hydration medium. The stability and size parameters were critically monitored. The liposomal systems were also studied for hepatoprotective activity in mice against carbon tetrachloride induced hepatotoxicity and gastroprotective activity using the pyloric ligation method. The results indicate a significant effect of cholesterol on drug-entrapment and drug-leakage characteristics. The size distribution range was from 0.056-1.270 microns with the most frequent size ranging from 0.266-0.466 micron. The amount of drug loaded in these vesicles was approx. 90%. Lipid cholesterol mass ratio of 10:2 has a maximum entrapment of 87.2% (+/- 1.77). The results obtained from the in vivo studies indicate the improved performance of silymarin in liposomes at a level of 55.6% hepatoprotection in comparison to 33.08% of plain drug. Plain liposomes showed hepatoprotection though to a lower degree of 24.2%. Liposomal silymarin and plain liposomes also showed significant antiulcer activity as compared with plain silymarin and control groups.