苦参碱醇质体的制备及其体外透皮性能

Preparation and in vitro percutaneous permeation profile of matrine ethosomes

背景:醇质体是一种新型脂质体,具有高变形性、高包封率的优点,能完整地透过皮肤,尤其适合作为外用给药和透皮给药载体。目的:采用卵磷脂和乙醇制备苦参碱醇质体,观察其在体外大鼠皮肤的透皮性能。设计、时间及地点:对比观察实验,于2007-08/2008-03在中南大学卫生部肝胆肠外科研究中心实验室完成。材料:苦参碱原料药由西安华鹏天然植物开发有限公司生产。大豆卵磷脂由美国AvantiPolarLipidsInc.生产。方法:苦参碱醇质体由10～30g/L卵磷脂、体积分数为30%～45%的乙醇、10g/L苦参碱和水组成,采用乙醇注入超声法制备。采用Franz扩散池检测体外透皮效果,供给池给药后,从接收池取样采用高效液相法检测药物透皮量。主要观察指标:苦参碱醇质体的粒径、包封率及苦参碱在体外大鼠皮肤的透皮量。结果:醇质体的粒径随乙醇体积分数增加而下降,随磷脂质量浓度增加而增加。与其他剂型相比,苦参碱醇质体的24h透皮累积量(60.5%)最大,而没有透皮延迟时间。结论:成功制备了苦参碱醇质体,其在体外实验中能增加苦参碱的经皮渗透性。

BACKGROUND： Ethosome is a new liposome with high deformability, high entrapment efficiency and permeating completely through skin. It is especially suitable for the carrier of external administration and cutaneous penetration. OBJECTIVE： To prepare matrine ethosomes and evaluate the percutaneous permeation profile in vitro on rat＇s skin. DESIGN, TIME AND SETTING： A comparison observation experiment was performed in the Laboratory of National Hepatobiliary ＆ Enteric Surgery Research Center, Central South University from August 2007 to March 2008. MATERIALS： Raw material of matrine was produced by Xi＇an Huapeng Natural Production Co., Ltd. Soybean lecithin was the production of American Avanti Polar Lipids Inc. METHODS： Matrine ethosomes comprised 10-30 g/L of lecithin, 30%-45% （v/v） ethanol, 10 g/L matrine and water, which were prepared by ethonal infusion and ultrasonic method. The percutaneous permeation of matrine ethosomes was evaluated with a Franz diffusion cell, matrine concentration was detected by HPLC from the examples of a receiving cell after administration at a supplying cell. MAIN OUTCOME MEASURES： The size entrapment efficiency and erythema index variation in vitro on rats of matrine ethosomes. RESULTS： The mean size of matrine ethosomes decreases with increasing ethanol concentrations whereas it increases as phospholipid concentrations increase, and the entrapment efficacy increases with increasing ethanol and phospholipids concentrations. The matrine ethosomes showed a permeation profile with a maximal cumulative amount of matrine permeated after 24 hours of 60.5% of the applied dose, and no lag time. CONCLUSION： The matrine ethosomes were successfully prepared, which showed an increase of the percutaneous permeation of matrine in vitro.