Transdermal on-demand drug delivery based on an iontophoretic hollow microneedle array system.
Transdermal on-demand drug delivery based on an iontophoretic hollow microneedle array system.
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DOI：
10.1039/d3lc00160a
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发表时间：
2023-04
期刊：
影响因子：
6.1
通讯作者：
Usanee Detamornrat;Marc Parrilla;Juan Domínguez-Robles;Q. K. Anjani;E. Larrañeta;K. De Wael;R. Donnelly
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文献类型：
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作者：
Usanee Detamornrat;Marc Parrilla;Juan Domínguez-Robles;Q. K. Anjani;E. Larrañeta;K. De Wael;R. Donnelly
透皮药物递送已经成为治疗药物的替代给药途径，克服了口服和肠胃外给药的当前问题。然而，这种技术受到皮肤角质层的低渗透性的阻碍。在这项工作中，我们开发了两种增强技术的协同组合，以通过与中空微针（HMN）耦合的离子电渗系统来改善和按需给药。第一次，设计了一种与集成离子电渗耦合的聚合物HMN阵列，用于递送带电分子和大分子（例如蛋白质）。为了证明这一概念，首先使用1.5%琼脂糖凝胶模型在体外设置中测试了亚甲蓝、荧光素钠、盐酸利多卡因和牛血清白蛋白-异硫氰酸荧光素缀合物（BSA-FITC）。随后，使用Franz扩散池进行离体药物渗透研究，在施加1 mA cm-2电流6 h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61倍、43倍、54倍和17倍。此外，分析了递送的药物总量（即在皮肤和受体隔室中），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）中提供了该概念的完整实现。总的来说，IHMAS设备提供了一种多功能的可穿戴技术，用于经皮按需给药，可以改善个性化剂量的给药，并有可能提高精准医疗。
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 stratum corneum 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 (e.g. 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 in vitro setup using 1.5% agarose gel model. Subsequently, the ex vivo 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-2 current for 6 h. Moreover, the total amount of drug delivered (i.e. 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.