目的 制备中华眼镜蛇神经毒素（NT）可溶性微针（DMNs-NT），并考察其理化性质及体外透皮性能。方法 采用两步离心法制备DMNs-NT，并以微针针体的成形性、机械强度及背衬层的柔韧性为指标，考察硫酸软骨素（CS）与聚乙烯吡咯烷酮（PVP k30）的比例、基质液含水量、背衬层材料；HPLC法测定其载药量，正置光学显微镜表征，并考察稳定性；采用Franz扩散池考察其体外透皮性能。结果 通过单因素考察确定DMNs-NT制备的最佳处方工艺为CS与PVP K30比例1∶1、基质材料与加水量比例5∶4、以羧甲基纤维素（CMC）为背衬层材料。DMNs-NT针体呈四棱锥形，表面平整，长度约为500 μm，每片含药量为（15.4±0.5）μg，药物位于针体上部，3个月内稳定性良好。离体皮肤渗透结果显示，4 h后DMNs-NT中NT的累积渗透量可达95.8%，而NT溶液几乎没有透过皮肤，证明可溶性微针对NT透皮递送具有良好的促进作用，能有效穿透大鼠离体皮肤。结论 制备DMNs-NT机械强度及柔韧性好，实现了大分子药物NT的透皮递送。

Objective To prepare Naja atra neurotoxin (NT) loaded dissolving microneedles (DMNs-NT), and investigate the physicochemical properties and in vitro transdermal properties. Methods DMNs-NT was prepared by a two-step centrifugation method. The ratio of CS and PVP K30, the water content of the matrix solution, and the backing layer material were optimized by the indexes of formability and mechanical strength of the microneedles and flexibility of the backing layer. The drug loading content was determined by HPLC, and the morphological characteristics were observed under an optical microscope, and the stability was also examined. Franz diffusion cell was used to investigate its in vitro skin permeation characteristics. Results Through the single-factor exploration, we confirmed that the optimal prescription technique for DMNs-NT preparation was a 1:1 ratio of CS and PVP k30, a 5:4 ratio of matrix material and water, with CMC as the backing layer material. The DMNs-NT had a pyramidal shape with a smooth surface and a length of approximately 500 μm. The drug loading content of per tablet was (15.4±0.5) μg. The drug was located in the upper part of the needle. DMNs-NT had good stability within 3 months. The results of in vitro skin permeation assay showed that the cumulative penetration of NT in DMNs-NT could reach 95.8% in 4 h, while NT solution barely penetrated the skin, which proved that it had a good promoting effect on NT transdermal delivery. Conclusion In this study, DMNs-NT had good mechanical properties and good skin penetration, which realized the transdermal drug delivery of macromolecular drugs.

R283.6

浙江省自然科学青年基金项目资助（LQ19H280004）；浙江省中医药优秀青年人才基金项目（2018ZQ013）；浙江省台州市科技计划项目（1701KY18）；浙江省药学会科研资助项目（2016ZYY27）；浙江省新苗人才计划项目资助（2019R410057）；浙江中医药大学2018年度校级科研基金（2018ZJ09）