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智能微針?biāo)幬镞f送系統(tǒng)是一種利用微小的針狀結(jié)構(gòu)穿透皮膚表層，實(shí)現(xiàn)藥物的經(jīng)皮給藥和控制釋放的技術(shù)，可以提高藥物的生物利用度和治療效果，同時(shí)減少藥物的副作用和給藥次數(shù)。智能微針?biāo)幬镞f送系統(tǒng)通常由可溶性或可降解性的材料制成，可以根據(jù)皮膚內(nèi)的溫度、pH值、酶活性、氧化還原應(yīng)激等刺激來(lái)響應(yīng)性地釋放藥物。

智能微針?biāo)幬镞f送系統(tǒng)用于銀屑病的治療的案例：

可溶性微針貼片，通過(guò)透皮給藥及胞內(nèi)遞送的分級(jí)遞藥策略，實(shí)現(xiàn) CRISPR/Cas9基因編輯系統(tǒng)對(duì)皮下免疫細(xì)胞和角質(zhì)形成細(xì)胞內(nèi)NLRP3基因的高效編輯，有效提高了銀屑病和特異性皮炎的糖皮質(zhì)激素療法。該可溶性微針貼片可以在皮膚內(nèi)形成納米級(jí)的基因編輯復(fù)合物，并在靶細(xì)胞內(nèi)釋放出Cas9核酸酶和NLRP3靶向sgRNA，從而實(shí)現(xiàn)NLRP3基因的敲除。該可溶性微針貼片可以顯著抑制銀屑病和特異性皮炎的炎癥反應(yīng)，并且對(duì)正常組織無(wú)毒副作用。

活性氧響應(yīng)凝膠微針貼片同時(shí)遞送抗細(xì)胞增殖藥物甲氨蝶呤（MTX）和活性氧清除藥物EGCG用于銀屑病的聯(lián)合治療。該活性氧響應(yīng)凝膠微針貼片可以在銀屑病皮膚內(nèi)與基座分離，并根據(jù)皮膚內(nèi)活性氧水平來(lái)控制MTX和EGCG的釋放。該活性氧響應(yīng)凝膠微針貼片可以顯著改善和延長(zhǎng)銀屑病的治療效果，并且對(duì)正常組織無(wú)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.

參考文獻(xiàn)：

[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