目的 阐明全缘千里光碱（integerrimine，INT）脂质体及其凝胶剂的离体皮肤渗透与滞留特性，探讨该制剂皮肤应用的作用机制。方法 制备INT脂质体、脂质体凝胶剂与普通凝胶剂；建立离体皮肤渗透接收液与皮肤中药物含量测定的HPLC方法；采用Franz扩散池法测定各种制剂与不同理化参数脂质体的药物离体皮肤渗透与滞留，并通过比较测定结果探讨制剂的作用机制。结果 成功制备并表征3种制剂。渗透接收液与皮肤中INT含量测定的HPLC法准确、精密。3种制剂的药物皮肤透过量均较小；应用12 h后皮肤滞留量：优化脂质体＞脂质体凝胶剂＞普通凝胶剂（2.59∶1.75∶1，P＜0.01），在角质层下皮肤滞留量：优化脂质体＞脂质体凝胶剂＞普通凝胶剂（2.54∶1.72∶1，P＜0.01），而角质层药物滞留量占全皮约为60%，且制剂间无显著性差异。包封率高的脂质体具有较高的角质层药物滞留。结论 脂质体通过与皮肤的相互作用可促进INT进入皮肤，是有毒药物皮肤局部作用的良好载体，而凝胶基质减小脂质体促进药物进入皮肤。

Objective To elucidate the ex vivo skin permeation and deposition characteristics of integerrimine (INT) liposomes and their gels, and to explore the action mechanism of the formulations after skin application. Methods Three types of formulations (liposomes, liposome gels and general gels) of INT were prepared. HPLC methods were developed for the determination of drug content in both receptor medium for ex vivo skin permeation tests and skin. The Franz diffusion cell method was used to determine the ex vivo skin permeation and deposition of the drug in the three types of formulations and liposomes with different physicochemical parameters, and the mechanism of action of the formulations was explored by comparing the results of the determination. Results The three types of formulations were successfully prepared and characterized. The HPLC methods for the determination of INT content were accurate and precise. The drug quantity permeated across skin of the three types of formulations was small. After application for 12 h, the drug deposition in whole skin and skin under the stratum corneum (SC) of the three types of formulations was both in the order of optimized liposomes > liposomal gels > ordinary gels (P < 0.01) with ratio of 2.59:1.75:1 and 2.54:1.72:1 respectively, while drug quantity deposited in SC accounted for about 60% of that in the whole skin, and there was no significant difference among the formulations. Liposomes with high encapsulation efficiency have higher drug deposition in SC. Conclusion Liposomes can promote INT to enter the skin by interaction with the skin, and they are desirable carriers for toxic drugs to achieve local effects on the skin, while gel matrix deters liposomes from promoting drug entry into skin.

R283.6

国家自然科学基金项目（82174096）；浙江省大学生科技创新活动计划暨新苗人才计划（2022R410A024）