目的 制备光甘草定醇质体与立方液晶纳米粒，通过测定2种纳米制剂在离体豚鼠皮肤中的滞留量优选出适合光老化经皮给药的制剂。建立光老化模型，通过观察优选制剂对豚鼠光老化模型的治疗效果来评价药物的疗效。方法 采用注入法制备光甘草定醇质体，高压均质法制备光甘草定立方液晶纳米粒，利用Franz扩散装置考察光甘草定醇质体、立方液晶纳米粒凝胶离体鼠皮中的滞留量，优选出光甘草定经皮给药治疗光老化的纳米制剂。紫外线照射背部剃毛豚鼠建立皮肤光老化模型。雌性豚鼠随机分为模型组、基质（给予空白凝胶0.5 g/只）组、维甲酸（阳性对照，0.5 g/只）组和甘草定立方液晶纳米粒凝胶高、低剂量（0.50、0.25 g/只）组，治疗2周后，通过肉眼观察、HE染色、Masson染色等评价其治疗效果，用水份测定仪观察其对豚鼠皮肤含水量的影响。结果 2种纳米制剂凝胶的鼠皮滞留量最高者为光甘草定立方液晶纳米粒凝胶。豚鼠皮肤光老化模型建立成功，HE染色、Masson染色等结果表明光甘草定立方液晶纳米粒对光老化有明显的治疗效果，使光老化皮肤的含水量显著升高（P<0.05）。结论 光甘草定立方液晶纳米粒在离体鼠皮中的滞留较高，对豚鼠皮肤光老化模型治疗效果显著，为光甘草定的临床应用提供了新的方法与思路。

Objective To prepare the ethosomes and cubic liquid crystalline nanoparticles of glabridin and selecte the suitable formulation for transdermal delivery by determining the skin retention amount of two nanopreparations in guinea pig skin. To establish photoaging models and the efficacy of the drug was evaluated by observing the therapeutic effect of the optimized preparation on the photoaging model of guinea pigs. Methods Ethosomes of glabridin were prepared by injection method. High pressure homogenization combined with heat was used to prepare cubic liquid crystalline nanoparticles of glabridin. The nanopreparation of glabridin was optimized by investigating the skin retention amount of ethosomes of glabridin gel and cubic liquid crystalline nanoparticles of glabridin gel in guinea pig skin. Expose the guinea pigs to UV-A and UV-B light to establish the animal model of guinea pig skin photoaging. Female guinea pigs were randomly divided into six groups:model group, matrix (blank gel 0.5 g), retinoic acid (positive control group, 0.5 g) and glycyrrhizin cubic liquid crystalline nanoparticles gel high and low dose (0.50, 0.25 g) group. After two weeks of treatment, the therapeutic effect was evaluated by naked eye observation, HE staining and Masson staining. The water content of guinea pig skin was observed by moisture analyzer. Results The higher skin retention amount of the two kinds of nano gel in guinea pigs skin was cubic liquid crystalline nanoparticles of glabridin gel. The photoaging model of guinea pig skin was successfully established. HE staining and Masson staining showed that the Cubic liquid crystalline nanoparticles of glabridin gel had obvious therapeutic effect on photoaging, and the water content of photoaging skin was significantly increased (P<0.05). Conclusion The cubic liquid crystalline nanoparticles of glabridin gel have a higher skin retention amount in the skin of guinea pigs in vitro,which has a remarkable therapeutic effect on photoaging of guinea pigs. It provided a new method and idea for the clinical application of glabridin.

R965

国家自然科学基金青年科学基金项目（81602773）