Investigation Of Preparation And Pharmac-Okinetics For Oxymatrine Liposome

Oxymatrine(OM) is a alkaloid of quinolizidine group, extracted from a traditional Chinese medicine, Ku-dou-zi or the aired root of Sophora flavescens ait..The studies of pharmacological have shown that OM has wide pharmacological effects including anti-arrhythmic, anti-inflammatory, anti-tumor, immunol-ogical enhancement. At present, OM is widely used for the treatment of chronic type B hepatitis, but OM injection used clinically has some disadvantages including short half-life, low drug concentration in tissues.Liposomes are well recognized as drug delivery vehicles that have target effents, delayed drug release and degraded drug toxicity. Thus, in this study we intend to prepare the OM liposome(OM-L) to improve its pharmacokinetics characters such as half-life and target effect and enhance therapeutic efficacy.We had applied a pH-gradient method to prepare OM-L. Through orthogonal experimental design, one optimum recipes of OM-L was founded that showed OM/EPC 1:10, EPC/Ch 3:1, pH 6.8, incubation tempreture 60℃. Under the optimal formulation, OM was encapsulated 51.35%.A method was developed for the determination of OM concentration in liposomes and entrapment efficiency and biological samples by HPLC, it was proved that this method was accurate, sensitive, specific and good enough to be used in pharmacokinetic study of OM. The small unilamellar vesicle liposomes were observed by transmission electron microscope. The mean particle diameter is about 80nm. The stability of OM-L was valuated with the entrapment efficiency and preoxidation value in 4, 25℃for 1 month. The results showed that the OM-L stored in 4℃would keep stability.The pharmacokinetic parameters and tissues distribution of OM water solution or OM-L were studied after intravenous administration OM or OM-L to rabbits and mice, respectively. The experimental results showed that the concentration-time curves of OM-L fit in a two-compartement model. To compare with water solution, biological half-life of liposomes prolonged 54 min in rabbits plasma and the concentrations of OM in liver, lung, spleen of mice were improved obviously. The result of pharmacokinetics and tissues distribution showed that OM-L had better tissues targeting and slow-release effect than OM.