Open AccessTransscleral Iontophoresis for Noninvasive Ocular Drug Delivery of Macromolecules
Author(s) -
Sarah Molokhia,
Kongnara Papangkorn,
Charlotte Butler,
John W. Higuchi,
Balbir Brar,
Balamurali K. Ambati,
S. Kevin Li,
William I. Higuchi
Publication year - 2020
Publication title -
journal of ocular pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 61
eISSN - 1557-7732
pISSN - 1080-7683
DOI - 10.1089/jop.2019.0081
Subject(s) - iontophoresis , in vivo , sclera , ophthalmology , medicine , drug delivery , pharmacology , chemistry , biomedical engineering , biology , microbiology and biotechnology , organic chemistry , radiology
Purpose: The objectives were to investigate the effect of transscleral iontophoresis of macromolecules in vitro and in vivo , to study the importance of electroosmosis on macromolecules of low charge to mass ratio, and to evaluate transscleral iontophoresis efficacy in a choroidal neovascularization (CNV) animal model. Methods: Through in vitro transport experiments, the permeability coefficients of macromolecules [eg, immunoglobulin G (IgG), dextran 70 kDa] were determined under different conditions. The effect of ionic strength formulations and iontophoretic conditions was studied on the distribution of IgG and bevacizumab into the eye in vivo . Magnetic resonance imaging (MRI) was utilized to evaluate in vivo real time distribution of gadolinium-labeled albumin (Galbumin) following iontophoresis. The efficacy between no treatment, intravitreal injection (IVT), and iontophoresis of bevacizumab on a CNV model of subretinal injection of adeno-associated virus encoding human VEGF-165 was investigated. Results: The permeability data suggested a significant effect of ionic strength on the iontophoretic transport of macromolecules. Transscleral iontophoresis of IgG at 4 mA with a low ionic strength formulation was about 600 times greater than passive diffusion and 14-fold over a conventional formulation in vitro . Approximately 0.6 mg of bevacizumab can be delivered into the rabbit eye in vivo with a 20-min treatment of iontophoresis. MRI showed that Galbumin was in the posterior tissues after iontophoresis. In the CNV model, the iontophoresis and IVT methods of bevacizumab delayed retinal neovascularization by 4 and 8 weeks, respectively. Conclusions: Transscleral iontophoresis is capable of delivering macromolecule drugs through the conjunctiva and sclera, eventually exposing the retina/choroid to the drugs.