Iontophoretic ocular delivery of latanoprost-loaded nanoparticles via skin-attached electrodes

Prolonged drug efficacy to reduce the number of administrations is a key factor in the successful treatment of glaucoma through topical drug delivery to the eye. Therefore, we propose a new strategy for iontophoretic ocular delivery of drug-loaded nanoparticles. Considering safety and convenience, our strategy is involved with topical administration of the drug-loaded nanoparticles followed by their permeation into the eye tissues via noninvasive iontophoresis, using the skin-attached electrodes. Thus, those nanoparticles stayed longer in the eye, and during this period, the drug was released in a sustained manner, thereby prolonging drug exposure even with one-time treatment. The nanoparticles were made of poly(lactic-co-glycolic acid) (PLGA), which were loaded with a glaucoma drug, latanoprost. We varied the size of the nanoparticles at 100, 200, 300, and 500 nm and sought to find the optimum size under the fixed conditions for iontophoresis proposed in this work (4 mA; 30 min). Even with iontophoresis through the skin-attached electrodes, the nanoparticles were indeed deposited in the eye tissues, where with an increase in particle size, drug release was more sustained, but fewer particles could permeate into the eye tissues. Because of these two competing factors, iontophoretic delivery of the 300-nm particles exhibited the most prolonged drug efficacy in vivo for more than 7 days, and showed an approximately 23-fold increase in drug efficacy compared with that of Xalatan (R), a commercially available eye drop of latanoprost developed for once-a-day administration every day. Statement of significance To treat glaucoma, conventional eye drops are often prescribed; however, they often require multiple daily administrations due to rapid preocular clearance. To resolve this, we suggest a noninvasive iontophoretic ocular delivery of latanoprost-loaded PLGA nanoparticles using the skin-attached electrodes. Even with iontophoresis via the skin-attached electrodes, the nanoparticles can indeed be deposited into the eye tissues. However, with an increase in particle size, fewer particles can permeate into the eye tissues, although drug release is more sustained. Therefore, the particles with a size of 300 nm show the optimal in vivo delivery profile in this work, where the drug efficacy can be extended for more than 7 days with a single administration. (C) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.