难溶性多西紫杉醇的溶解微针制备及体外评价

Preparation and in vitro evaluation of insoluble docetaxel loaded dissolving microneedle

目的:制备一种用于透皮给药的负载多西紫杉醇(DTX)的溶解微针,并进行体外评价。方法:考察不同材料及配方制备DTX溶解微针(DTX-MN),通过外观和力学性能指标对微针进行表征,测定微针针头载药量。使用猪皮肤考察微针溶解性能。剥离小鼠腹部皮肤,进行体外透皮吸收研究,初步考察DTX-MN给药后的皮肤药代动力学。结果:成功制备了针头完整、力学性能良好的DTX-MN,最佳工艺得到的微针针头载药量为(14.81±4.20)μg (n=5),微针能完整插入皮肤穿透角质层屏障,且在10 min内完全溶解。体外透皮实验显示,DTX-MN的初始透皮速率和累积透皮通量都高于药物溶液组,相比溶液组,DTX-MN在24 h后累积渗透量提高了3.27倍,其释放机制符合Fickian扩散。结论:制备的DTX-MN有良好的穿刺皮肤的性能,能够显著促进DTX的透皮递送,该类微针有望促进DTX的浅表皮肤递送,具有潜在的临床应用价值。

OBJECTIVE To prepare a dissolving microneedle loaded with docetaxel(DTX) for transdermal delivery and evaluate its quality in vitro.METHODS The DTX dissolving microneedle(DTX-MN) was prepared with different materials and formulations. The microneedle was characterized by appearance and mechanical properties, and the drug loading of microneedle was determined by using.porcine skin to investigate the solubility of microneedle. The abdominal skin of mice was peeled off and the transdermal absorption in vitro was studied to preliminarily investigate the skin pharmacokinetics of DTX-MN.RESULTS DTX-MN with intact needle and good mechanical properties was successfully prepared. The drug loading of needle obtained by the optimum process was(14.81±4.20) μg(n=5). The microneedle could completely insert into skin, penetrate the stratum corneum barrier and completely dissolve in 10 min. The in vitro transdermal experiment showed that the initial transdermal rate and cumulative transdermal flux of DTX-MN were higher than those of drug solution. Compared with the solution, the cumulative permeation amount of DTX-MN increased by 3.27 times after 24 hours, and its release mechanism conformed to a Fickian diffusion model.CONCLUSION The prepared DTX-MN has good skin puncture performance, and can significantly promote the transdermal delivery of DTX. This kind of microneedle is expected to promote the superficial skin delivery of DTX with potential clinical application value.