目的 研究石杉碱甲水凝胶微针的制备条件，并考察微针的性能及其经皮给药的可行性。方法 采用聚乙烯醇和葡聚糖混合水凝胶作为微针的基质材料，考察材料的溶胀性能和拉伸性能，确定最优处方；以两步夹心法将石杉碱甲药粉载入微针基质材料中，采取离心及冷冻-解冻工艺制备针形为圆锥体，针长为500 μm，针间距为1000 μm的水凝胶微针阵列，并对其机械性能、皮肤穿刺性能进行评价；建立石杉碱甲质量分析方法，采用改良的Franz扩散池对载药微针阵列进行体外透皮释药性能考察。结果 得到的最优处方：聚乙烯醇与葡聚糖质量比为9∶1，0.15 g/mL混合溶液作为针尖材料，0.08 g/mL混合溶液作为阵列基底材料；每根微针可承受大于0.5 N的极限压力，表明微针可成功穿刺角质层，进入皮内；体外透皮实验表明，72 h内石杉碱甲的累积透皮率达85%以上。结论 以聚乙烯醇和葡聚糖这2种复合高分子材料制备的石杉碱甲水凝胶微针阵列，具有良好的机械性能和皮肤穿刺性能，为难溶性药物石杉碱甲实现高效、无痛经皮缓释给药，提高患者依从性提供了一种新的可能。

Objective To investigate the preparation conditions of hydrogel microneedles loaded huperzine A, and examine the performance of microneedles as well as the feasibility of percutaneous drug delivery. Methods Polyvinyl alcohol (PVA) and dextran mixed hydrogel were used as the matrix material of the microneedles. The swelling performance and tensile properties of the material were investigated to determine the optimal prescription. The huperzine A powder was loaded into the microneedles matrix material by a two-step sandwiching method. The hydrogel microneedle array with the cone-like-shaped needles, 500 μm in length and 1000 μm in needle spacing, was prepared by centrifugation and freeze-thawing process. The mechanical properties and skin penetration performance of the drug-loaded microneedle array were evaluated. The quality analysis method of huperzine A was established, and the in vitro transdermal release behavior of the drug-loaded microneedles was investigated by a modified Franz diffusion cell. Results The optimal prescription was as follows: the mass ratio of polyvinyl alcohol to dextran was 9:1, 0.15 g/mL mixed solution was used as the needle tip material, and 0.08 g/mL mixed solution was used as the array substrate material. Each microneedle can withstand the ultimate pressure greater than 0.5 N, indicating that the microneedle can successfully puncture the stratum corneum and enter the skin. In vitro transdermal test showed that the cumulative transdermal rate of huperzine A reached more than 85% within 72 h. Conclusion The hydrogel microneedle array prepared with two kinds of composite polymer materials, polyvinyl alcohol and dextran, had good mechanical and skin puncture properties, which provided a new possibility to realize efficient, painless, and percutaneous sustained-release for the insoluble drug huperzine A, as well as improve patient compliance greatly.

R283.6

浙江省自然科学基金资助项目（LY20H300005）