智能微针药物递送系统是一种利用微小的针状结构穿透皮肤表层，实现药物的经皮给药和控制释放的技术，可以提高药物的生物利用度和治疗效果，同时减少药物的副作用和给药次数。智能微针药物递送系统通常由可溶性或可降解性的材料制成，可以根据皮肤内的温度、pH值、酶活性、氧化还原应激等刺激来响应性地释放药物。

智能微针药物递送系统用于银屑病的治疗的案例：

可溶性微针贴片，通过透皮给药及胞内递送的分级递药策略，实现 CRISPR/Cas9基因编辑系统对皮下免疫细胞和角质形成细胞内NLRP3基因的高效编辑，有效提高了银屑病和特异性皮炎的糖皮质激素疗法。该可溶性微针贴片可以在皮肤内形成纳米级的基因编辑复合物，并在靶细胞内释放出Cas9核酸酶和NLRP3靶向sgRNA，从而实现NLRP3基因的敲除。该可溶性微针贴片可以显著抑制银屑病和特异性皮炎的炎症反应，并且对正常组织无毒副作用。

活性氧响应凝胶微针贴片同时递送抗细胞增殖药物甲氨蝶呤（MTX）和活性氧清除药物EGCG用于银屑病的联合治疗。该活性氧响应凝胶微针贴片可以在银屑病皮肤内与基座分离，并根据皮肤内活性氧水平来控制MTX和EGCG的释放。该活性氧响应凝胶微针贴片可以显著改善和延长银屑病的治疗效果，并且对正常组织无毒副作用。
Intelligent microneedle drug delivery system is a technique that uses tiny needle-like structures to penetrate the skin to achieve transdermal delivery and controlled release of drugs, which can improve the bioavailability and therapeutic effect of drugs, while reducing the side effects and number of doses. Intelligent microneedle drug delivery systems are usually made of soluble or biodegradable materials that can release drugs in response to the temperature, pH, enzyme activity, redox stress and other stimuli.

Case of an intelligent microneedle drug delivery system for the treatment of psoriasis:

Soluble microneedle patch, through transdermal administration and keratinocytes, effectively improved glucocorticoid therapy for psoriasis and specific dermatitis. The soluble microneedle patch can form nanoscale gene-editing complexes within the skin and release Cas 9 nuclease and NLRP 3 targeting sgRNA in target cells, thus enabling NLRP 3 gene knockout. This soluble microneedle patch can significantly inhibit the inflammatory response of psoriasis and specific dermatitis, and has no toxic side effects on normal tissues.

The reactive oxygen gel microneedle patch simultaneously delivers the anticellular proliferation drug methotrexate (MTX) and the reactive oxygen species scavenging agent EGCG for the combined treatment of psoriasis. This ROS-responsive gel microneedle patch can be separated from the base within psoriatic skin and control MTX and EGCG release based on intracutaneous ROS levels. This ROS-responsive gel microneedle patch can significantly improve and prolong the therapeutic effect of psoriasis, and has no toxic side effects on normal tissues.

参考文献：

[1]Donnelly, R. F., Singh, T. R., Tunney, M. M., & Morrow, D. I. (2010). Microneedle-mediated transdermal and intradermal drug delivery. John Wiley & Sons. https://doi.org/10.1002/9780470665521

[2] Wang, Y., Zhang, Y., Zhang, Y., Liu, J., Zhang, Y., Wang, L., … & Ping, Y. (2021). Dissolving Microneedle Patches for Transcutaneous and Intracellular Delivery of CRISPR/Cas9 System to Treat Inflammatory Skin Diseases. ACS nano, 15(2), 2764-2777. https://doi.org/10.1021/acsnano.0c10768

[3]Bi, D., Liu, Y., Zhu, J., & Liu, Y. (2021). Reactive Oxygen Species-Responsive Gel-Based Microneedle Patches for Prolonged and Intelligent Psoriasis Management. ACS nano, 15(3), 4898-4910. https://doi.org/10.1021/acsnano.2c08979