Dissolving microneedle patches loaded with resveratrol albumin nanoclusters for corneal anti-angiogenic therapy.

Corneal neovascularization (CNV) is a leading cause of corneal blindness. Although resveratrol (RES) effectively inhibits neovascularization, its clinical utility remains severely limited by poor aqueous solubility and low permeability across ocular surface barriers. To address these challenges, we developed dissolving microneedle patches encapsulating RES-loaded bovine serum albumin nanoclusters (RES-NC@MN). Specifically, we fabricated RES-NCs via a microfluidic-assisted nanoprecipitation method and systematically optimized the formulation using a three-factor Box-Behnken design. The optimized RES-NCs exhibited uniform spherical nanostructures (∼158 nm) with high encapsulation efficiency. XRD and DSC analyses confirmed the amorphous state of the encapsulated drug. The resulting RES-NC@MNs demonstrated sufficient mechanical strength for corneal insertion and facilitated rapid drug release. Notably, the steady-state flux of RES from RES-NC@MNs was approximately 10-fold higher than that from RES suspensions. Pharmacokinetic studies revealed that RES-NC@MNs achieved a 7.2-fold increase in Cmax and a 26.5-fold greater AUC0-∞ compared to conventional RES suspensions. In a rat alkali-burn model, treatment with these MNs reduced the neovascular area by approximately 70% and significantly suppressed CD31 and VEGF expression alongside pro-inflammatory cytokine levels. Consequently, the RES-NC@MN system presents a robust strategy for delivering lipophilic therapeutics to the ocular surface, offering enhanced anti-angiogenic efficacy for CNV treatment.