目的 研究雷公藤甲素双室可溶性微针制备工艺，并进行质量评价及体外透皮性能的考察。方法 以硫酸软骨素（chondroitin sulfate，CS）与羟丙基甲基纤维素（hydroxypropyl methylcellulose，HPMC）为针尖材料，聚乙烯吡咯烷酮（polyvinylpyrrolidone，PVP）K30与聚乙烯醇（polyvinyl alcohol，PVA）为背衬材料。采用两步离心法制备双室载药微针，单因素试验及Box-Behnken设计-响应面法，优选针尖层、背衬层工艺参数。光学显微镜、电子扫描显微镜表征双室载药微针，倒置荧光显微镜观察药物分布，HPLC法测定载药量，大鼠体内外皮肤穿刺考察机械性能；采用Franz扩散池考察其体外透皮性能。结果 双室载药微针的最优处方为40%乙醇-水溶液为药物溶剂；针尖工艺参数：HPMC与CS的比例为1∶4，材料与溶剂的比例为1∶1，针尖药物总质量浓度为6 mg/mL；背衬工艺参数：PVA与PVP K30的比例为1∶2，材料与溶剂的比例为1∶2，微针离心时间10 min，背衬药物总质量浓度为0.5 mg/mL。制备的双室载药微针外观形态、机械性能良好；针尖部位的药物主要分布于针尖尖端，背衬药物有些许下渗至针尖2/3处；每片含药量为（218.88±0.10）mg；体外透皮实验表明，72 h内雷公甲素累积透皮率达98%。结论 雷公藤甲素双室载药的设计，增大载药量的同时还具有良好的缓释作用，该设计可为中药微针的研究奠定实验基础。

Objective To study the preparation process of triptolide double-compartment dissolving microneedles, and to evaluate the quality and investigate the transdermal performance in vitro. Methods Chondroitin sulfate (CS) and hydroxypropyl methylcellulose (HPMC) were used as needle tip materials, and polyvinylpyrrolidone K30 (PVP K30) and polyvinyl alcohol (PVA) were used as backing materials. Two-step centrifugation method was used to prepare dual-chamber drug-loaded microneedles. Single factor experiment and Box-Behnken design response surface method were used to optimize the process parameters of tip layer and backing layer. The dual-chamber drug-loaded microneedles were characterized by optical microscope and electron scanning microscope. The drug distribution was observed by inverted fluorescence microscope. The drug loading was measured by HPLC. In vitro and in vivo skin puncture was used to investigate the mechanical properties. Franz diffusion cell was used to investigate its in vitro transdermal properties. Results The optimal formulation of dual-chamber drug-loaded microneedles was 40% ethanol water solution as drug solvent. Needle tip process parameters was that the ratio of HPMC to CS was 1:4, the ratio of material to solvent was 1:1 and the needle tip drug concentration was 6 mg/mL. Backing process parameters is that the ratio of PVA to PVP K30 was 1:2, the ratio of material to solvent was 1:2, the microneedle centrifugation time was 10 min and the drug concentration of the backing drug was 0.5 mg/mL. The prepared dual-chamber drug-loaded microneedles have good appearance and mechanical properties. The drug at the needle tip was mainly distributed at the tip of the needle tip and the backing drug was slightly infiltrated to 2/3 of the needle tip. The drug content of each tablet was (218.88 ±0.10) µg. The in vitro transdermal experiment showed that the cumulative transdermal rate of ratracin within 72 h reached 98%. Conclusion The double-chamber drug-loading design of triptolide can increase the drug-loading capacity and also has a good sustained-release effect, which can lay an experimental foundation for the research of traditional Chinese medicine microneedle.

R283.6

贵州省特色功能食品与中药制剂开发攻关大平台（黔教合KY字[2020]006）；贵州中医药大学药用高分子材料研究中心（贵中医党办发[2019]70号）；贵中医博士启动基金资助项目（［2021］14号）；贵州省国内一流学科建设项目（GNYL[2017]008）；贵州省药物新剂型新工艺科技创新人才团队项目（黔科合平台人才［2017］5655）