面向经皮给药的高分子可溶微针的优化设计与研究

Transdermal drug delivery offers the first choice over traditional drug delivery methods. The stratum corneum is the greatest barrier to transdermal transport. Polymer microneedle as a method for painlessly and transiently disrupting the stratum corneum barrier can facilitate the delivery of macromolecules. However, there are still several bottleneck issues which need to be addressed before their application, such as low drug loading (lower than 50 ug per 1 cm2 patch), poor drug stability (about 50% drug loss in microneedles), fast release of drug in the skin, etc. To address these issues, we will carry out this project as follows: (1) design and develop novel funnel based microneedles to increase the drug loading in microneedles (over than 500 ug per 1 cm2 patch); (2) microneedle and drug loaded nanoparticles fabrication process will be optimized to protect the drug in the development (over than 70% drug activity); and (3) drug loaded nanoparticles will be introduced in the microneedles to achieve long term release of drug from microneedles in the skin. All these studies will provide theoretical and technical support for further applications of microneedles in transdermal drug delivery.

与传统给药方式相比，经皮给药是临床上一些疾病治疗的首选。但皮肤尤其是角质层成为开发经皮给药制剂的重要屏障。高分子微针可在皮肤角质层上无痛地创造微米级药物输送通道，加速大分子药物的快速通过。但目前高分子微针给药仍有若干关键问题亟待解决，如载药量低（1 cm2微针贴片载药量通常小于50 μg）、微针制备过程药物活性损失较高（约50%）、药物在皮下释放速率过快等。本项目针对以上关键问题展开研究。重点研究：（1）设计并开发新型漏斗状微针结构，以大幅度增加微针载药量（1 cm2微针贴片载药量大于500 μg）；（2）系统研究高分子微针及载药纳米粒制备过程中影响药物活性损失的主要因素，提出优化的微针及载药纳米粒制备工艺及配方，使微针中药物活性在70%以上；（3）将载药纳米粒引入微针开发与制备，以达到微针快速溶解和药物在皮下缓速释放的效果。为高分子微针经皮给药的进一步推广及应用提供技术支持和理论基础

与传统给药方式相比，经皮给药是临床上一些疾病治疗的首选。但皮肤尤其是角质层成为开发经皮给药制剂的重要屏障。高分子微针可在皮肤角质层上无痛地创造微米级药物输送通道，加速大分子药物的快速通过。本项目设计并开发了两段式、气泡式微针，用于胰岛素药物的皮下传输，优化了微针制备工艺、探讨了药物在微针中稳定性的机理、研究了载药微针的结构与性能的关系、评价了高分子微针应用于人体的安全性。研究结果表明，本项目所开发的高分子微针可有效、安全地用于无痛皮下给药的传输系统。项目研究成果为高分子微针的临床应用提供了重要的数据支撑与技术基础。