In situ swelling of hydrogel microneedles facilitates suprachoroidal space expansion for targeted delivery of TOP-V122 to the posterior segment

Abstract

Posterior segment eye diseases are leading causes of vision impairment, yet current treatments such as intravitreal injections require frequent administration and carry risks of complications, including endophthalmitis and retinal detachment, highlighting the need for minimally invasive and controllable alternatives. Here, we present an improved hydrogel-forming microneedle (HFMN) platform composed of 20% poly(methyl vinyl ether-alt-maleic acid) and 7.5% poly(ethylene glycol) for minimally invasive, targeted drug delivery to the posterior segment via the suprachoroidal space. A dispensing-based drug-loading method reduced the required drug volume from 4 mL to 50 μL (∼80-fold), enabling precise dosing of expensive ophthalmic agents. We employed TOP-V122, a clinically relevant hydrophobic compound that releases nitric oxide and inhibits phosphodiesterase 5, addressing the limitations of prior hydrophilic model-drug studies. The platform exhibited sufficient mechanical strength for scleral penetration (2.49 N per needle) and biocompatibility (higher ARPE-19 cell viability than free drug). Validation included ex vivo drug permeation studies using Nile red as a fluorescent tracer, in vitro cytotoxicity assays, and a short-term in vivo rabbit feasibility study. The platform enabled rapid ex vivo V122 permeation across porcine scleral tissue, with 64.6 ± 10.5% of loaded drug detected within 30 min, and supported suprachoroidal space-associated fluorescence distribution after short-term ex vivo application. In the rabbit study, 15-min V122-HFMN application reduced intraocular pressure and increased ocular cyclic guanosine monophosphate levels, without overt acute histological damage at the insertion site. These findings support HFMNs as a promising platform for rapid, short-duration posterior segment therapy, potentially improving patient compliance and reducing healthcare burden.

Statement of significance

Treating posterior segment eye diseases remains a significant clinical challenge. Repeated intravitreal injections, the standard of care, carry risks of serious complications and impose a substantial burden on patients. Here, we present a hydrogel-forming microneedle platform that penetrates the sclera, swells upon contact with ocular fluid, and transiently opens the suprachoroidal space to enable drug delivery to the posterior segment. A dispensing-based drug-loading method reduces the required drug volume by approximately 80-fold, enabling precise dosing of costly therapeutics. Using a clinically relevant hydrophobic compound with dual vascular activity, we demonstrate rapid, short-duration drug delivery and preliminary outcomes comparable to intravitreal injection, with reduced tissue disruption. This platform offers a practical, minimally invasive alternative for managing blinding posterior segment diseases.