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基于电渗流中空微针阵列系统的按需透皮药物传递。

Transdermal on-demand drug delivery based on an iontophoretic hollow microneedle array system.

机构信息

School of Pharmacy, Medical Biology Centre, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.

A-Sense Lab, Department of Bioscience Engineering, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium.

出版信息

Lab Chip. 2023 May 2;23(9):2304-2315. doi: 10.1039/d3lc00160a.

Abstract

Transdermal drug delivery has emerged as an alternative administration route for therapeutic drugs, overcoming current issues in oral and parenteral administration. However, this technology is hindered by the low permeability of the of the skin. In this work, we develop a synergic combination of two enhancing technologies to contribute to an improved and on-demand drug delivery through an iontophoretic system coupled with hollow microneedles (HMNs). For the first time, a polymeric HMN array coupled with integrated iontophoresis for the delivery of charged molecules and macromolecules ( proteins) is devised. To prove the concept, methylene blue, fluorescein sodium, lidocaine hydrochloride, and bovine serum albumin-fluorescein isothiocyanate conjugate (BSA-FITC) were first tested in an setup using 1.5% agarose gel model. Subsequently, the drug permeation study using a Franz diffusion cell was conducted, exhibiting a 61-fold, 43-fold, 54-fold, and 17-fold increment of the permeation of methylene blue, fluorescein sodium, lidocaine hydrochloride, and BSA-FITC, respectively, during the application of 1 mA cm current for 6 h. Moreover, the total amount of drug delivered ( in the skin and receptor compartment) was analysed to untangle the different delivery profiles according to the types of molecule. Finally, the integration of the anode and cathode into an iontophoretic hollow microneedle array system (IHMAS) offers the full miniaturisation of the concept. Overall, the IHMAS device provides a versatile wearable technology for transdermal on-demand drug delivery that can improve the administration of personalised doses, and potentially enhance precision medicine.

摘要

经皮给药已成为治疗药物的一种替代给药途径,可克服口服和肠胃外给药的当前问题。然而,该技术受到皮肤渗透性低的限制。在这项工作中,我们开发了两种增强技术的协同组合,通过与中空微针(HMN)结合的离子电渗系统来促进改善和按需药物传递。这是首次设计出一种与集成离子电渗相结合的聚合物 HMN 阵列,用于输送带电分子和大分子(蛋白质)。为了验证这一概念,首先在 1.5%琼脂糖凝胶模型中使用 进行了亚甲蓝、荧光素钠、盐酸利多卡因和牛血清白蛋白-荧光素异硫氰酸酯缀合物(BSA-FITC)的测试。随后,使用 Franz 扩散池进行了 药物渗透研究,在施加 1 mA cm 电流 6 小时期间,亚甲蓝、荧光素钠、盐酸利多卡因和 BSA-FITC 的渗透分别增加了 61 倍、43 倍、54 倍和 17 倍。此外,分析了药物在皮肤和受体隔室中的总递送量( ),以根据分子类型解开不同的递送曲线。最后,将阳极和阴极集成到离子电渗中空微针阵列系统(IHMAS)中,实现了该概念的完全小型化。总体而言,IHMAS 装置为按需经皮药物递送提供了一种通用的可穿戴技术,可改善个性化剂量的管理,并有可能增强精准医学。

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