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

作者：Wangdu Luo, Fang Liu, Yi Lin, Junlong Yu, qianyi lin, Xin Liu, Yujie Rao, Jiaguo Yuan, Yan Zhang, Xiaomin Zhu, Xiangji Li, Lin Xie · 发表于：Biomedical Materials · 年份：2026 · DOI：10.1088/1748-605x/ae4a63 · 研究领域：Corneal Surgery and Treatments、Ocular Surface and Contact Lens、Advanced Drug Delivery Systems

Abstract To develop a poly(lactic-co-glycolic acid) (PLGA) nanoparticle system encapsulating the type II TGF- β receptor (T β RII)-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, and in vitro release. Uptake by human conjunctival fibroblasts (HConFs) was assessed by flow cytometry and confocal microscopy. In a TGF- β 2-induced fibrotic model, cytocompatibility, proliferation, migration, and expression of α -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- β 2-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 I...