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Our scrutiny centers on the substrate materials pivotal for microneedle construction and the core properties that dictate their efficacy. We delve into the distinctive interplay between microneedles and dermal layers, underscoring the mechanisms by which this synergy enhances drug absorption and precision targeting. Moreover, we examine the acupoint\u2013target organ\u2013ganglion nexus, an innovative strategy that steers drug concentration to specific targets, offering a paradigm for precision medicine. A thorough analysis of the clinical applications of polymeric microneedle systems is presented, highlighting their adaptability and impact across a spectrum of therapeutic domains. This review also accentuates the systems\u2019 promise to bolster patient compliance, attributed to their minimally invasive and painless mode of drug delivery. We present forward-looking strategies aimed at optimizing stimulation sites to amplify therapeutic benefits. The anticipation is set for the introduction of superior biocompatible materials with advanced mechanical properties, customizing microneedles to cater to specialized clinical demands. In parallel, we deliberate on safety strategies aimed at boosting drug loading capacities and solidifying the efficacy of microneedle-based therapeutics. In summation, this review accentuates the pivotal role of polymeric microneedle technology in contemporary healthcare, charting a course for future investigative endeavors and developmental strides within this burgeoning field.<\/jats:p>","DOI":"10.3390\/polym16182568","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T05:45:12Z","timestamp":1726033512000},"page":"2568","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Polymeric Microneedle Drug Delivery Systems: Mechanisms of Treatment, Material Properties, and Clinical Applications\u2014A Comprehensive Review"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0451-184X","authenticated-orcid":false,"given":"Yun","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiyue","family":"Mao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijia","family":"Han","sequence":"additional","affiliation":[{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiancheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1007\/s13346-020-00710-x","article-title":"Development and clinical study of the use of infrared radiation to accelerate the dissolution rate of a microneedle array patch (MAP)","volume":"3","author":"Park","year":"2020","journal-title":"Drug Deliv. 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