Abstract
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Silymarin has hepatoprotective properties and is used in treatment of various liver diseases, but its bioavailability from oral products is very poor. In order to overcome its poor oral bioavailability we have prepared silymarin loaded hepatic targeting liposomes suitable for parenteral administration. The liposomal formulations were composed of hydrogenated soy phosphatidylcholine and cholesterol with or without distearoylphosphoethanolamine-(polyethyleneglycol)-2000 and various amounts of β-sitosterol β-d-glucoside (Sito-G) as the hepatic targeting moiety. Increasing the amount of Sito-G in the liposomes gradually decreased drug encapsulation efficiencies from ∼70% to ∼60%; still showing promising drug encapsulation efficiencies. Addition of Sito-G to non-PEGylated liposomes clearly affected their drug release profiles and plasma protein interactions, whereas no effect on these was seen for the PEGylated liposomes. Non-PEGylated liposomes with 0.17M ratio of Sito-G exhibited the highest cellular drug uptake of 37.5% for all of the studied liposome formulations. The highest cellular drug uptake in the case of PEGylated liposomes was 18%, which was achieved with 0.17 and 0.33M ratio of added Sito-G. The liposome formulations with the highest drug delivery efficacy in this study showed hemolytic activities around 12.7% and were stable for at least 2months upon storage in 20mM HEPES buffer (pH 7.4) containing 1.5% Polysorbate 80 at 4°C and room temperature. These results suggest that the Sito-G containing liposomes prepared in this work have hepatic targeting capability and that they are promising candidates for delivering silymarin to the liver.