Department of Mechanical Engineering, The University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, British Columbia V6T 1Z4, Canada.
Department of Dermatology, University of California San Francisco, San Francisco, CA 94143, USA.
Int J Pharm. 2023 May 10;638:122885. doi: 10.1016/j.ijpharm.2023.122885. Epub 2023 Apr 2.
Microneedles (MNs) are needles with a tip diameter ranging from 10 to 100 um and a length ranging up to 1 mm. The first patent for drug delivery device for percutaneous administration filed by Alza corporation dates back to 1976 (Gerstel and Place, 1976), and in between 1989 and 2021 the filed patents for MNs are >4500 [1]. These devices can potential overcome some drawbacks of traditional needles, such as the pain generated during insertion, requirement for trained personnel to manipulate syringes, and difficulty of performing injections in elderly and obese patients. MNs and MN arrays are emerging as a convenient method to deliver compounds and extract blood without causing any pain. A promising application is the use of MNs as alternative solution to topical creams (TC) and transdermal patches (TP) for transdermal drug delivery. The external layer of human skin, the epidermis, offers a major barrier to transdermal drug delivery, thanks to the stratum corneum (SC). Exposed to the external environment, SC ultimately protects the human body from UV light radiation, heat, water loss, bacteria, fungi and viruses, and it is the barrier that controls diffusion rate for almost all compounds. TC and TP applications are limited by the skin permeability to lipophilic compounds and small molecules, and by the slow delivery rate of some compounds. MNs have been around for >35 year now, and it is a general opinion that MNs increase delivery compared to passive diffusion, thanks to the feature of penetrating the SC and reaching the dermis. This review recollects the existing studies that compare MN delivery of drugs with passive diffusion of the same drugs in alive organisms, giving an overview of what are the type of MNs, the chemical delivered and the methods employed to quantify drug delivery into skin and/or in the bloodstream. The final aim is to quantify the enhancement factor of MNs with respect to passive diffusion, and establish a possible standard on how tests can be performed in order to compare different data.
微针（MNs）是一种针尖直径为 10 至 100μm，长度可达 1mm 的针。Alza 公司于 1976 年首次为经皮给药的药物输送装置申请专利（Gerstel 和 Place，1976），1989 年至 2021 年期间，MN 的已申请专利超过 4500 项[1]。这些装置可以克服传统针的一些缺点，例如插入时产生的疼痛、需要训练有素的人员来操作注射器以及在老年和肥胖患者中进行注射的困难。MNs 和 MN 阵列正在成为一种方便的方法，可以在不引起疼痛的情况下输送化合物和提取血液。一个有前途的应用是将 MNs 用作替代局部乳膏（TC）和透皮贴剂（TP）的方法，用于经皮药物输送。人体皮肤的外层表皮，由于角质层（SC）的存在，为经皮药物输送提供了主要的屏障。暴露于外部环境中，SC 最终保护人体免受紫外线辐射、热量、水分流失、细菌、真菌和病毒的侵害，它是控制几乎所有化合物扩散速率的屏障。TC 和 TP 的应用受到亲脂性化合物和小分子的皮肤渗透性以及某些化合物的缓慢输送速率的限制。MNs 已经存在了 35 年以上，人们普遍认为，MNs 比被动扩散更能增加药物的输送，这要归功于穿透 SC 到达真皮的特性。本综述回顾了将 MN 输送药物与活体生物中相同药物的被动扩散进行比较的现有研究，概述了 MN 的类型、输送的化学物质以及用于量化药物输送到皮肤和/或血液中的方法。最终目的是量化 MN 相对于被动扩散的增强因子，并建立一种可能的标准，说明如何进行测试以比较不同的数据。
