可分离近红外光诱导热熔性微针透皮给药机制研究

Microneedle transdermal delivery systems are one kind of important research fields for the drug safety and efficient delivery due to their advantages of minimally invasive, painless and convenient. However, the disadvantages including the low preparation efficiency, passive delivery manner and uncontrolled release of drugs according to the individual physiological conditions or external specific stimulus using current microneedle drug delivery systems have severely restricted them to practical applications. In this project, development of separable and near-infrared (NIR) induced thermal ablation microneedle systems prepared by 3D printing technology has been proposed for blood glucose control on diabetic rats. The research works including the design composition and structure of microneedle materials, preparation of microneedles by 3D printing technology, break the interfaces and delivery barriers, structure-activity relationship of microneedles and a series of simulation experiments in vitro and in vivo, will be carried out in this project. In addition, the mechanism of transdermal delivery of drugs, pharmacological and pharmacokinetics effects will be further explored. The successful implementation of this project will promote to develop a new NIR-responsive microneedle transdermal delivery system, a new strategy for transdermal drug delivery with active manner. The results obtained from this project will also provide theoretical and experimental supports for the development of microneedle transdermal delivery.

微针透皮给药具有微创、无痛、方便等优势，是实现药物安全、高效递送的重要研究方向。但当前微针给药系统存在制备效率低下、药物被动给药为主及难以依据个体生理条件的变化或外界特定刺激实现程序可控主动释药等缺陷。本项目拟以可分离近红外光诱导热熔性微针透皮给药为主要目标、以糖尿病实验鼠的血糖控制为基本模型，从微针针体材料的设计、微针的3D打印制备及体外、体内模拟给药实验等步骤，研究微针载体材料结构、界面与突破载运屏障，提高药物递送效率的构效关系，在此基础上进一步探究药物利用可分离近红外光诱导热熔性微针的载运递送机制及透皮给药的时效和量效关系。从而发展基于近红外光诱导微针热熔的透皮给药新系统，实现主动调控微针负载药物释放的新方法，构筑新的微针透皮给药新策略。为发展微针透皮给药的新理论、新方法和新材料提供理论支持和实验依据。

针对当前微针给药系统制备效率低下、被动给药为主及难以依据个体生理条件的变化或外界特定刺激实现程序可控主动释药等缺陷，本项目拟以近红外光响应调控微针经皮给药为主要目标，从微针针体材料的设计、经皮给药系统的3D打印制备及体外、体内模拟给药实验等步骤，研究微针载体材料结构、界面与突破载运屏障，提高药物递送效率的构效关系，在此基础上进一步探究药物的载运递送机制及经皮给药的时效和量效关系。重点开展了以下几方面的研究工作：（1）通过材料的选择与设计，制备具有近红外光诱导热熔性微针针体材料；（2）利用生物3D打印技术制备药物负载的可分离式微针，探寻负载药物对近红外光诱导热熔释放机制；（3）建立糖尿病实验动物模型，研究近红外光诱导热熔性微针经皮给药的载运递送机制及给药的时效和量效关系。从而发展新型的基于对近红外光响应微针经皮给药新系统，主动调控微针负载药物释放的新方法，构筑新的微针透皮给药新策略。本项目的主要研究成果已在Chem. Eng. J.、Acta Biomater.、Biomater. Sci.、Bio-Des. Manuf.、Macromol. Rapid Commun.（封面论文）、ACS Biomater. Sci. Eng.、Mater. Sci. Eng. C、ACS Appl. Bio Mater.、Biomed. Microdevices、Biomed. Phys. Eng. Express、J. Bionic Eng.、Front. Mater. Sci.（封面论文）、生物工程学报、中国生物医学工程学报、高分子学报等国内外学术期刊录用和发表SCI/EI论文21篇，申请发明专利10项，已获授权发明专利5项，培养博士/硕士研究生8名。获科技成果奖1项，国内外学术会议报告5次，圆满完成项目的预期所有目标，并拓展了微针介导药物递送在血糖水平调控、肿瘤治疗、血尿酸调控、皮肤创口修复等领域的应用研究。