A PLGA-based aptamer delivery system for modulating subconjunctival fibrosis after glaucoma filtration surgery

To develop a poly(lactic-co-glycolic acid) (PLGA) nanoparticle system encapsulating the type II TGF-βreceptor (TβRII)-targeting aptamer S58 (PLGA-S58) and evaluate its ability to mitigate subconjunctival fibrosis after glaucoma filtration surgery. PLGA-S58 was prepared by double emulsion-solvent evaporation and characterized for morphology, size, encapsulation efficiency, andin vitrorelease. Uptake by human conjunctival fibroblasts (HConFs) was assessed by flow cytometry and confocal microscopy. In a TGF-β2-induced fibrotic model, cytocompatibility, proliferation, migration, and expression ofα-smooth muscle actin (α-SMA) and type I collagen were evaluated.In vivo, a rat glaucoma filtration surgery model was established, and S58 or PLGA-S58 was administered subconjunctivally at the filtration site. Bleb morphology and intraocular pressure (IOP) were monitored for 30 d, and tissue fibrosis was assessed by histology and immunofluorescence. PLGA-S58 nanoparticles were spherical with a hydrodynamic size of 255-295 nm and an encapsulation efficiency of ∼66%. PLGA-S58 showed sustained release over 7 d (∼71% cumulative release at 168 h) while preserving aptamer integrity. Compared with free S58, PLGA-S58 more effectively suppressed TGF-β2-induced HConF proliferation, migration, and fibrotic marker expression. In rats, PLGA-S58 formed a local depot detectable for ⩾7 d, produced more diffuse and longer-lasting filtering blebs, achieved greater and more stable IOP reduction over 30 d, and reduced collagen deposition andα-SMA-positive myofibroblast accumulation in the filtration area. PLGA-S58 enables sustained local delivery of a TβRII-targeting aptamer and improves antifibrotic efficacy and bleb function after filtration surgery, supporting translational potential as a safer alternative to cytotoxic antimetabolites.