Finerenone liposome-embedded dissolving microneedles: A transcorneal platform for minimally invasive therapy of diabetic retinopathy

Diabetic retinopathy (DR) is a leading cause of vision loss characterized by retinal neovascularization and chronic inflammation. Conventional topical therapies exhibit poor corneal bioavailability and rapid precorneal clearance. Herein, we engineered a dissolvable microneedle patch incorporating finerenone-loaded liposomes (FIN-LIP@MNs) to simultaneously overcome drug solubility limitations and epithelial barrier constraints. The optimized liposomal formulation exhibited a mean diameter of 128.6 nm and high encapsulation efficiency (84.5%). PXRD and DSC further confirmed that the incorporated drug existed in an amorphous state. The MNs were characterized by drug enrichment at the needle tips, sufficient mechanical strength to penetrate the cornea, and complete dissolution within 15 min. In vivo pharmacokinetic studies showed that FIN-LIP@MNs achieved a 28.4-fold higher Cmax and a 26.9-fold greater AUC0~∞ in aqueous humor compared with conventional eye drops, along with a prolonged mean residence time (6.3 h). Retinal delivery was also markedly enhanced, with Cmax and AUC0~∞ increasing by 22.4-fold and 47.7-fold, respectively. In a db/db mouse model of DR, FIN-LIP@MNs restored retinal laminar architecture, rescued pericyte-endothelial homeostasis, reduced acellular capillaries by 53.8%, and markedly suppressed retinal CD31, VEGF, and inflammatory cytokines. This "liposome-in-microneedle"platform provides a minimally invasive and patient-friendly strategy for anti-angiogenic and anti-inflammatory therapy in DR.