苦参碱醇质体的制备☆

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：制备苦参碱醇质体并评价其在大鼠皮肤中的在体抗炎活性。设计、时间及地点：随机对照动物实验，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：采用乙醇注入法与超声法结合制备苦参碱醇质体。方法：采用激光动态散射仪检测醇质体粒径；超速离心法检测包封率；采用反射分光光度仪检测苦参碱制剂在体抗炎活性。主要观察指标：苦参碱醇质体的粒径、包封率及大鼠在体皮肤的红斑指数变化。结果：苦参碱醇质体平均粒径为50~200 nm，粒径分布窄，包封率为40%~90%。空白醇质体的红斑指数变化与生理盐水溶液比较没有显著差异（P > 0.05），而水-乙醇溶液与空白醇质体或生理盐水溶液相比有显著性差异(P < 0.01)。苦参碱醇质体与苦参碱非醇质体制剂相比能更快地消退红斑；空白醇质体既没有诱发红斑作用也没有抗炎活性。结论：苦参碱醇质体的平均粒径依赖于其组成，随乙醇体积分数增加而减小，随磷脂质量浓度增加而增加；而包封率随乙醇和磷脂水平增加而增加。空白醇质体作为皮肤传递载体在大鼠皮肤显示有良好的耐受性；苦参碱醇质体能增强苦参碱对在体大鼠皮肤诱发红斑的抗炎活性。

Preparation of matrine ethosomes

BACKGROUND: Ethosome is a new liposome with high deformability, high entrapment efficiency and permeating completely through skin. It is suitable for the carrier of external administration and cutaneous penetration.OBJECTIVE: To prepare matrine ethosomes and evaluate the anti-inflammatory activity in vivo on rat skin.DESIGN, TIME AND SETTING: The experiment, a randomized controlled study, was carried out in Laboratory of National Hepatobiliary & Enteric Surgery Research Center, Central South University from August 2007 to March 2008.MATERIALS: Matrine ethosomes were prepared by ethanol infusion and ultrasonic method.METHODS: The size of matrine ethosomes was measured by laser light scattering technique and entrapment efficiency with ultracentrifugation. Reflectance spectrophotometry was used to evaluate the anti-inflammatory activity of matrine formulations.MAIN OUTCOME MEASURES: The size, entrapment efficiency and erythema index variation in vivo on rats of matrine ethosomes.RESULTS: Matrine ethosomes had mean sizes ranging from 50 nm to 200 nm, a narrow size distribution and entrapment efficiency ranging from 40% to 90%. There was not significantly difference between erythema index variation of empty ethosomes and that of saline solution (P > 0.05), but it was significantly different for water-ethanol solution to empty ethosomes or water-ethanol solution to saline solution (P < 0.01). Matrine ethosomes were able to reduce the erythema more rapidly with respect to the matrine solutions of free ethosomes. Induced erythema or anti-inflammatory activities were not observed for empty ethosomes.CONCLUSION: 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 could improve anti-inflammatory activity of matrine for induced erythema of rat skin in vivo.