目的 制備光甘草定醇質(zhì)體與立方液晶納米粒，通過測定2種納米制劑在離體豚鼠皮膚中的滯留量優(yōu)選出適合光老化經(jīng)皮給藥的制劑。建立光老化模型，通過觀察優(yōu)選制劑對(duì)豚鼠光老化模型的治療效果來評(píng)價(jià)藥物的療效。方法 采用注入法制備光甘草定醇質(zhì)體，高壓均質(zhì)法制備光甘草定立方液晶納米粒，利用Franz擴(kuò)散裝置考察光甘草定醇質(zhì)體、立方液晶納米粒凝膠離體鼠皮中的滯留量，優(yōu)選出光甘草定經(jīng)皮給藥治療光老化的納米制劑。紫外線照射背部剃毛豚鼠建立皮膚光老化模型。雌性豚鼠隨機(jī)分為模型組、基質(zhì)（給予空白凝膠0.5 g/只）組、維甲酸（陽性對(duì)照，0.5 g/只）組和甘草定立方液晶納米粒凝膠高、低劑量（0.50、0.25 g/只）組，治療2周后，通過肉眼觀察、HE染色、Masson染色等評(píng)價(jià)其治療效果，用水份測定儀觀察其對(duì)豚鼠皮膚含水量的影響。結(jié)果 2種納米制劑凝膠的鼠皮滯留量最高者為光甘草定立方液晶納米粒凝膠。豚鼠皮膚光老化模型建立成功，HE染色、Masson染色等結(jié)果表明光甘草定立方液晶納米粒對(duì)光老化有明顯的治療效果，使光老化皮膚的含水量顯著升高（P<0.05）。結(jié)論 光甘草定立方液晶納米粒在離體鼠皮中的滯留較高，對(duì)豚鼠皮膚光老化模型治療效果顯著，為光甘草定的臨床應(yīng)用提供了新的方法與思路。

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

國家自然科學(xué)基金青年科學(xué)基金項(xiàng)目（81602773）