微针技术应用研究现状_赵思博.pdf

第 23 卷第 2 期2023年 2月过 程 工 程 学 报The Chinese Journal of Process EngineeringVol.23 No.2Feb.2023Current application and development of microneedleSibo ZHAO,Yiru BAO,Min XIE*State Chemical Experiment Teaching Demonstration Center,College of Chemistry and Molecular Science,Wuhan University,Wuhan,Hubei 430072,ChinaAbstract:Microneedles are micrometer sized single needles or needle arrays that are produced by microfabricating techniques.Microneedles could penetrate the stratum corneum layer of the skin to reach the dermal layer which is favorable for percutaneous drug delivery.Microneedles have a number of advantages in drug delivery,compared with oral administration,microneedles circumvent the metabolic effects of the digestive system on drugs,compared with injection needles,microneedles are able to reduce pain and improve adherence compliance in patients.Due to their special transdermal pathway and precise,convenient application methods,microneedle has also become a hot studies area in biomedicine at present and their applications in vaccination,tissue fluid extraction and biomarker detection,etc.have been well investigated.According to working mechanisms for percutaneous drug delivery,microneedles can be classified as five kinds,including solid,coated,dissolving,hollow,and hydrogel microneedles.This review,combined with relevant articles in the field of microneedle technology in recent years,provides a brief overview of the types and fabricating materials of microneedles,mainly introduces the current applications of microneedles in the field of drug delivery(such as insulin injection for diabetes treatment,local drug delivery for cancer treatment,vaccination,tissue fluid extraction and biomarker detection,etc.)Besides,if the microneedles would be widely applied in the marker for medical application,some factors including mechanic strength,biological safety,sterilization process and biological stability of biomolecules on the micrneedles should be well considered which are also discussed in the review.At last,outlooks on microneedles future development are prospected,such as developing microneedles based drug delivery system for heart attack treatment,improving biological stability of the biological molecules on the microneedles for convenient vaccination,and combining of microneedles with other techniques,such as sensitive biomarker detection method,microfluidic chip and wearable device,which will open a new prospect for the development of microneedles techniques.Key learning points:(1)Microneedle is a minimally invasive,convenient,precise,effective and advanced medical technology.(2)Microneedles are prepared from various materials such as metal,glass,silicon,ceramic,stainless steel or biodegradable materials.(3)Based on working mechanism,microneedles can be classified as five types which are solid,coated,dissolving,hollow,and hydrogel microneedles.(4)Microneedle is widely used in drug delivery,vaccination,tissue fluid extraction,as well as biomarker detection,etc.Key words:microneedle;transdermal technology;working mechanism;medical application;future development综述DOI:10.12034/j.issn.1009-606X.222114收稿：2022-04-02，修回：2022-05-11，网络发表：2022-05-24；Received:2022-04-02,Revised:2022-05-11,Published online:2022-05-24基金项目：国家自然科学基金资助项目(编号：21575100；21974098)；武汉大学实验教学中心开放实验项目(编号：WHU-2021-XYKF-04)；武汉大学2022年教学研究项目“面向专业需求的大学化学实验课程体系建设”作者简介：赵思博，化学生物学专业，E-mail:；通讯联系人，谢敏，副教授，研究领域为纳米传感和生物医学分析，E-mail:引用格式引用格式：赵思博,鲍怡如,谢敏.微针技术应用研究现状.过程工程学报,2023,23(2):163172.Zhao S B,Bao Y R,Xie M.Current application and development of microneedle(in Chinese).Chin.J.Process Eng.,2023,23(2):163172,DOI:10.12034/j.issn.1009-606X.222114.过 程 工 程 学 报第 23 卷 微针技术应用研究现状赵思博，鲍怡如，谢 敏*武汉大学化学与分子科学学院，国家级化学实验教学示范中心，湖北 武汉 430072摘要：微针是通过微制造加工获得的一种针状体，单个针体尺寸为微米级，多个针体组成微针阵列，能够穿透皮肤角质层直达真皮层，在研发初期主要用于药物递送。与口服给药相比，微针能避开消化系统对药物的代谢作用；与注射针头相比，微针能够有效减小患者疼痛感，提高患者依从性。此外，微针技术因为其便捷的透皮作用方式，在疫苗接种、组织液提取、生物标志物检测、医疗美容等领域的应用也被广泛开发。微针的制作材料有硅、不锈钢及生物降解材料，如透明质酸、聚乳酸等；从给药方式上可分为固体、包被、溶解、空心以及水凝胶等多种微针类型。本综述结合近年来微针技术相关进展，简要概述微针的制造材料及作用形式，重点介绍微针在药物递送、疫苗接种及组织液提取和生物标志物检测等领域的应用，探讨微针的机械强度、生物安全性、无菌化处理及稳定性等对其在市场上推广应用的影响，并对其未来发展进行了展望。要点：(1)微针技术是一种微创、便捷而精确有效的先进医疗技术。(2)微针由金属、玻璃、硅、陶瓷、不锈钢或生物降解材料等多种材料制备而成。(3)根据作用模式，微针包括固体、包被、溶解、空心和水凝胶微针五种类型。(4)微针技术广泛应用于药物递送、疫苗接种、组织液提取以及生物标志物检测等领域。关键词：微针；透皮技术；工作原理；医学应用；未来发展中图分类号：R318 文献标识码：A 文章编号：1009-606X(2023)020163101 前 言 微针是通过微制造加工而成的一种针状体，针头直径多为几十微米，长度一般为几十微米至几毫米，多以单针体或多针体阵列形式存在。微针可进行皮肤穿刺，因其微创、便捷、而又精确有效的作用模式，已广泛用于药物递送、疫苗接种、组织液提取、生物标志物检测等。以药物递送为例，微针可穿透皮肤角质层直达真皮层，形成微米尺寸给药通道，使药物递送更精准快速、剂量更稳定。相比口服给药，微针能避开消化系统对药物的代谢；相比肌肉注射，微针能减少疼痛，提高依从性。因此，微针作为一种新兴透皮技术在医疗领域具有广阔发展前景。微针可由金属、玻璃、硅、陶瓷、不锈钢或生物降解材料(如透明质酸、聚乳酸)等，通过蚀刻1-3、激光切割模具4、金属电镀5、光刻6等技术制备而得；按透皮作用方式，主要分为五类：固体微针、包被微针、溶解微针、空心微针、水凝胶微针。该技术最早出现于1976年7，但由于微加工技术的匮乏，直到20世纪90年代才得以推广。据中国知网()以及 Web of Science()的文献检索分析，微针技术相关研究在近二十年来发表文章数量逐年升高，十分具有发展前景(图1和2)。本综述对近年来具有代表性的微针研究进行梳理归纳，简要概述微针的透皮作用方式及制作材料，重点归纳微针的应用研究现状，并对微针技术及应用中可能存在的问题进行探讨，对未来发展方向进行展望。2 微针分类 当前，根据微针透皮给药的作用方式，可将微针分为五类：固体微针、包被微针、溶解微针、空心微针和水198019851990199520002005201020152020020406080100