Studies on the encapsulation of oxymatrine into liposomes by ethanol injection and pH gradient method

Oxymatrine is the major active alkaloid constituent extracted from traditional Chinese herb medicine Sophora flavescens Ait (Kushen) and Sophora alopecuroides (Kudouzi). In recent years, oxymatrine had been found to posses remarkable anti-hepatic activity and has been used for treating hepatitis B in clinical therapy in China. In this study, we attempted to entrap oxymatrine into liposomes to facilitate the delivery of oxymatrine to the liver and enhance the therapeutic efficiency for hepatitis. Preformulation investigation was performed to obtain the drug physicochemical properties such as solubility, pKa, and logP for rational liposomes preparation design. Liposomes were prepared with soybean lecithin by ethanol injection and pH gradient loading methods. At the same time the factors affecting the entrapment efficiencies were investigated and compared. Ethanol injection method yielded liposomes with entrapment efficiency less than 20%. The lipid composition and aqueous medium had some effects on entrapment efficiency. However, liposomes could be produced with entrapment efficiency above 50% by pH gradient method. The internal pH buffer capacity, the lipid composition, and drug-to-lipid ratio greatly influenced the entrapment efficiency, while the incubation temperature had almost no effect on entrapment efficiency in the active loading procedure.