微针阵列技术对纳米粒经皮给药的促透作用探究.pdfVIP

微针阵列技术对纳米粒经皮给药的促透作用研究 Enhancement of transdermal nanoparticles delivery by microneedles 1 2 2 高静 张玮 高申 1. 第二军医大学药学院2. 第二军医大学附属长海医院药学部 课题所属基金项目：国家自然基金（项目编、上海市自然基金（项目编号10ZR1437300）；通讯作者：高申，男， 1957-，教授，博士生导师，主要从事经皮给药及靶向制剂的研究 [摘要] ：目的：考察微针阵列对纳米粒经皮给药的促渗作用，以及纳米粒在接收液和皮肤中的分布。方法：采用双荧光探针 指示纳米粒的经皮过程，采用Franz 扩散池法，将裸鼠皮肤置于扩散池间，微针组供给室加入纳米粒混悬液，皮肤采用微针 阵列作用；对照组皮肤无微针作用。采用共聚焦显微镜观察纳米粒在皮肤内的渗透过程，采用HPLC 法测定纳米粒的分布。 结果：共聚焦显微镜观察显示纳米粒经由微针作用皮肤后产生的微孔渗透进入皮肤。与对照比较，微针可以显著增加纳米粒 在皮肤内的滞留量，但纳米粒不能穿透皮肤进入接受液中；纳米粒在表皮层中的滞留量大于真皮层。结论：微针作用皮肤后 可显著增加纳米粒的皮肤内递送，有利于局部皮肤给药。 [关键字] ：皮肤；微针；PLGA ；纳米粒；局部给药 ABSTRACT Objective: This study was to investigate penetration and distribution of Poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles in the skin treated with microneedles. Methods: Double fluorescent PLGA nanoparticles were prepared to indicate the transdermal transport process of the nanoparticles. Permeation study was performed on Franz-type diffusion cells in vitro. Penetration of nanoparticles was visualized by confocal laser scanning microscopy (CLSM). Distribution of nanoparticles was quantified by HPLC. Results: The CLSM images revealed that nanoparticles were delivered into the microconduits created with microneedles and penetrate into epidermis and dermis. The quantitative results showed that, (i) Amount of nanoparticles penetrating into the skin was enhanced by using microneedles, but no nanoparticles reached the receptor compartment, (ii) much more nanoparticles deposited in epidermis than in dermis. Conclusion: These results suggested that microneedles were able to enhance intradermal PLGA nanoparticles delivery, and the nanoparticles would deposit in the skin and sustain drug release over a prolonged period. This strategy was potentially employed for topical drug administration. Keywords ：skin; microneedles; PLGA; nanoparticles; topical drug delivery