目的 制备冰片修饰根皮素醇质体（borneol-modified phloretin ethosomes，Bor-Phl-ES），考察其体外释药行为和经皮渗透性能。方法 薄膜分散法制备Bor-Phl-ES；选择磷脂与胆固醇用量比、脂药比和丙二醇体积分数为主要影响因素，以Bor-Phl-ES包封率、载药量和粒径的总评归一值（overall desirability，OD）作为响应值，Box-Behnken设计-效应面法优化Bor-Phl-ES处方；采用卡波姆940作为基质将Bor-Phl-ES制备成凝胶，透析法考察其体外释药行为，透射电子显微镜观察微观外貌，并对Bor-Phl-ES凝胶进行流变学研究；Franz扩散池法考察Bor-Phl-ES凝胶透皮性能。结果Bor-Phl-ES最佳处方：磷脂与胆固醇用量比为13.6∶1，脂药比为11.7∶1，丙二醇体积分数为31%；Bor-Phl-ES的平均包封率为（81.92±1.07）%，载药量为（6.16±0.07）%，粒径为（179.44±6.76）nm，ζ电位为（−10.89±0.91）mV；Bor-Phl-ES形态为球形或椭圆形；Bor-Phl-ES凝胶24 h累积释放度为77.96%，释药行为符合Higuchi模型；流变学研究显示，Bor-Phl-ES凝胶具有固体弹性性质；透皮试验研究表明，Bor-Phl-ES凝胶将根皮素透皮速率、单位面积累积渗透量和皮肤滞留量分别提高至4.32、4.17、3.35倍。结论Bor-Phl-ES凝胶缓释特征明显，药物透皮渗透速率高且稳定，有效促进了根皮素透皮吸收。

Objective To prepare borneol-modified phloretin ethosomes (Bor-Phl-ES), and to study its drug release in vitro and transdermal permeation properties. Methods Bor-Phl-ES was prepared by film dispersion method. Phospholipid to cholesterol ratio, lipids to drug ratio, volume fraction of propylene glycol were selected as main influencing factors, overall desirability (OD) of entrapment efficiency, drug loading and particle size acted as response values, Box-Behnken design-response surface method was used to optimize preparations of Bor-Phl-ES. Bor-Phl-ES gel was prepared using carbomer 940 as matrix, and drug release in vitro was studied by dialysis method. Microscopic appearance of Bor-Phl-ES was observed by transmission electron microscopy (TEM), and rheology of Bor-Phl-ES gel was also studied. Franz diffusion cell method was used to study the transdermal properties of Bor-Phl-ES gels. Results The optimal formulation of Bor-Phl-ES: phospholipid to cholesterol ratio was 13.6:1, lipids to drug ratio was 11.7:1, volume fraction of propylene glycol was 31%. Average encapsulation efficiency, drug loading, particle size and ζ potential of Bor-Phl-ES were (81.92 ±1.07)%, (6.16 ±0.07)%, (179.44 ±6.76) nm, and (−10.89 ±0.91) mV, respectively. Shape of Bor-Phl-ES was spherical or elliptical, cumulative release rate of Bor-Phl-ES gel at 24 h was 77.96%, which accorded with Higuchi model. Rheological properties of Bor-Phl-ES gels showed solid elastic properties. Transdermal test results showed that Bor-Phl-ES gel increased the permeation rate, cumulative penetration and skin retention of phloretin to 4.32, 4.17 and 3.35 times, respectively. Conclusion Bor-Phl-ES gel had obvious sustained-release characteristics, transdermal drug penetration rate was high and stable, and the transdermal permeation of phloretin was promoted effectively by Bor-Phl-ES gel.

R283.6

2023年度河南省高等学校重点科研项目(23B320013);2024年度河南省医学教育研究项目(WJLX2024211);2024年度郑州市社科调研课题项目(ZSKL20241285);河南应用技术职业学院青年骨干教师资助项目(2022-GGJS-Y003);河南应用技术职业学院首席技师资助项目(2023-SXJS-HL02)