Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Department of Surgery, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Adv Mater. 2022 Feb;34(5):e2107315. doi: 10.1002/adma.202107315. Epub 2021 Dec 8.
Iontophoresis is an electrical-current-based, noninvasive drug-delivery technology, which is particularly suitable for intraocular drug delivery. Current ocular iontophoresis devices use low current intensities that significantly limit macromolecule and nanoparticle (NP) delivery efficiency. Increasing current intensity leads to ocular tissue damage. Here, an iontophoresis device based on a hydrogel ionic circuit (HIC), for high-efficiency intraocular macromolecule and NP delivery, is described. The HIC-based device is capable of minimizing Joule heating, effectively buffering electrochemical (EC) reaction-generated pH changes, and absorbing electrode overpotential-induced heating. As a result, the device allows safe application of high current intensities (up to 87 mA cm , more than 10 times higher than current ocular iontophoresis devices) to the eye with minimal ocular cell death and tissue damage. The high-intensity iontophoresis significantly enhances macromolecule and NP delivery to both the anterior and posterior segments by up to 300 times compared to the conventional iontophoresis. Therapeutically effective concentrations of bevacizumab and dexamethasone are delivered to target tissue compartments within 10-20 min of iontophoresis application. This study highlights the significant safety enhancement enabled by an HIC-based device design and the potential of the device to deliver therapeutic doses of macromolecule and NP ophthalmic drugs within a clinically relevant time frame.
电渗析是一种基于电流的非侵入式药物输送技术，特别适用于眼内药物输送。目前的眼部电渗析设备使用的电流强度较低，这极大地限制了大分子和纳米颗粒（NP）的输送效率。增加电流强度会导致眼部组织损伤。本文介绍了一种基于水凝胶离子电路（HIC）的电渗析设备，用于高效的眼内大分子和 NP 输送。基于 HIC 的设备能够最小化焦耳加热，有效缓冲电化学（EC）反应产生的 pH 变化，并吸收电极过电位引起的加热。因此，该设备允许安全地应用高电流强度（高达 87 mA cm ，比目前的眼部电渗析设备高 10 倍以上）到眼睛，而对眼部细胞死亡和组织损伤的影响最小。与传统电渗析相比，高强度电渗析可将大分子和 NP 的输送效率提高 300 倍以上，无论是在前节还是后节。贝伐单抗和地塞米松的治疗有效浓度在电渗析应用后 10-20 分钟内输送到目标组织隔室。本研究强调了基于 HIC 的设备设计所实现的显著安全性增强，以及该设备在临床相关时间内输送治疗剂量的大分子和 NP 眼科药物的潜力。
