@article{5d88cdf1f9bc4c988344b85109992b8e,
title = "A Hydrogel Ionic Circuit Based High-Intensity Iontophoresis Device for Intraocular Macromolecule and Nanoparticle Delivery",
abstract = "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−2, 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.",
author = "Fan Zhao and Shan Fan and Deepta Ghate and Svetlana Romanova and Bronich, {Tatiana K.} and Siwei Zhao",
note = "Funding Information: This research was supported by Departmental Start‐Up Fund provided by the Holland Regenerative Medicine Program at the University of Nebraska Medical Center. This research was also supported by the National Institute of General Medical Sciences, U54 GM115458, which funds the Great Plains IDeA‐CTR Network. The content in this publication was solely the responsibility of the authors and did not necessarily represent the official views of the NIH. The authors acknowledge the Nanomaterials Core Facility of the Center for Biomedical Research Excellence (CoBRE) and Nebraska Center for Nanomedicine supported by the Institutional Development Award from the National Institutes of General Medical Sciences (P30GM127200). The authors acknowledge Dr. Meghal Gagrani for the instruction of ocular tissue dissections; Dr. Wen Xue for the instruction of ELISA assay; Dr. Bo Liu for the instruction of nanoparticle fabrication; Dr. Cuifen Wang for the paraffin section and H&E staining of ocular tissues; and Dr. Mike Punsoni and Dr. Dominick J. Dimaio for the interpretation of ocular tissue damage from H&E staining images. Funding Information: This research was supported by Departmental Start-Up Fund provided by the Holland Regenerative Medicine Program at the University of Nebraska Medical Center. This research was also supported by the National Institute of General Medical Sciences, U54 GM115458, which funds the Great Plains IDeA-CTR Network. The content in this publication was solely the responsibility of the authors and did not necessarily represent the official views of the NIH. The authors acknowledge the Nanomaterials Core Facility of the Center for Biomedical Research Excellence (CoBRE) and Nebraska Center for Nanomedicine supported by the Institutional Development Award from the National Institutes of General Medical Sciences (P30GM127200). The authors acknowledge Dr. Meghal Gagrani for the instruction of ocular tissue dissections; Dr. Wen Xue for the instruction of ELISA assay; Dr. Bo Liu for the instruction of nanoparticle fabrication; Dr. Cuifen Wang for the paraffin section and H&E staining of ocular tissues; and Dr. Mike Punsoni and Dr. Dominick J. Dimaio for the interpretation of ocular tissue damage from H&E staining images. Note: The name of the author Tatiana K. Bronich was corrected on December 10, 2021, after initial publication online. Publisher Copyright: {\textcopyright} 2021 Wiley-VCH GmbH",
year = "2022",
month = feb,
day = "3",
doi = "10.1002/adma.202107315",
language = "English (US)",
volume = "34",
journal = "Advanced Materials",
issn = "0935-9648",
publisher = "Wiley-VCH Verlag",
number = "5",
}