赖氨酸在甘草次酸弹性囊泡形成过程中的作用机制  

Mechanism of Lysine on the Formation of Glycyrrhetic Acid Elastic Vesicles

作　　者：李爽[1,2] 邱玉琴[1] 张锁慧[1] 高云华[1] 

机构地区：[1]中国科学院理化技术研究所,光化学转换和功能材料重点实验室,北京100190 [2]中国科学院研究生院,北京100049

出　　处：《物理化学学报》2011年第9期2167-2172,共6页Acta Physico-Chimica Sinica

基　　金：国家自然科学基金(20975106)资助项目~~

摘　　要：制备和评价含赖氨酸的甘草次酸弹性囊泡, 并考察赖氨酸在囊泡形成过程中的作用机制. 在水合介质中加入赖氨酸, 利用薄膜-高压均质法制备甘草次酸弹性囊泡. 并合成了甘草次酸赖氨酸盐及其弹性囊泡作为对比制剂. 通过对粒径、zeta电位、包封率、相转变温度、变形性和体外经皮渗透性的测试, 考察赖氨酸在甘草次酸弹性囊泡中的存在形式及作用. 结果显示加入赖氨酸后, 甘草次酸弹性囊泡的粒径略有降低, 膜相转变温度降低, 包封率和囊泡变形性显著提高, 载药量提高近30倍(1.5 mg·mL-1), 并显著高于其赖氨酸盐所形成囊泡的载药量和弹性. 此外, 赖氨酸的加入使弹性囊泡的变形能力增加, 8 h累积透过量和皮肤驻留量分别提高4.3倍和9.2倍. 表明赖氨酸与甘草次酸形成离子缔合物, 促进甘草次酸参与膜的形成, 使膜的流动性增加, 赖氨酸与弹性囊泡对提高囊泡载药量起协同作用.Elastic vesicles of glycyrrhetic acid （GA） with lysine in the aqueous phase were prepared by the film-high pressure homogenization method. The influence of lysine on the formation of GA elastic vesicles was evaluated in this work. The lysine salt of GA was synthesized and entrapped in elastic vesicles as a control formulation. The particle size, zeta-potential, entrapment efficiency, phase transformation temperature, deformability of the elastic vesicles, and the permeation of GA through rat skin were investigated. By the incorporation of lysine into elastic vesicles the particle size decreased slightly and the phase transformation temperature decreased while the entrapment efficiency and deformability of the elastic vesicles increased obviously. The drug loading reached 1.5 mg · mL^-1, which was 30 times higher than that of GA elastic vesicles without lysine. The drug loading and deformability of the elastic vesicles was remarkably higher than that obtained using the lysine salt. In addition, the cumulative amount of GA permeation through rat skin within 8 h and the residual amount in the skin were found to be 4.3 times and 9.2 times higher than that of the vesicles without lysine, which was higher than that of the elastic vesicles with the lysine salt of GA. These results indicate that lysine forms an ion associate with GA, which takes part in the formation of vesicle membranes and subsequently increases the membrane＇s fluidity. Such a high drug loading capability is a result of the synergistic effect between lysine and the elastic vesicles.

关 键 词：甘草次酸 弹性囊泡 赖氨酸 载药量 机理 

分 类 号：TQ460.1[化学工程—制药化工]