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

Area of Science:

• Biomaterials Science
• Ophthalmology
• Nanotechnology

Background:

• Subconjunctival fibrosis is a major cause of failure after glaucoma filtration surgery.
• Current treatments often involve cytotoxic antimetabolites with significant side effects.
• Targeting the transforming growth factor-beta (TGF-β) pathway is a promising antifibrotic strategy.

Purpose of the Study:

• To develop poly(lactic-co-glycolic acid) nanoparticles encapsulating the TβRII-targeting aptamer S58 (PLGA-S58).
• To evaluate the antifibrotic efficacy of PLGA-S58 in vitro and in vivo after glaucoma filtration surgery.
• To assess the impact of PLGA-S58 on bleb function and intraocular pressure (IOP) reduction.

Main Methods:

• PLGA-S58 nanoparticles were prepared and characterized for size, morphology, and drug release.
• In vitro studies used human conjunctival fibroblasts (HConFs) in a TGF-β2-induced fibrotic model.
• In vivo studies utilized a rat glaucoma filtration surgery model with subconjunctival administration of S58 or PLGA-S58.

Main Results:

• PLGA-S58 nanoparticles demonstrated sustained release of S58 aptamer over 7 days.
• PLGA-S58 effectively suppressed HConF proliferation, migration, and fibrotic marker expression in vitro.
• In vivo, PLGA-S58 reduced collagen deposition and myofibroblast accumulation, improving bleb function and IOP control.

Conclusions:

• PLGA-S58 nanoparticles provide sustained local delivery of an antifibrotic aptamer.
• This system enhances antifibrotic efficacy and bleb function post-glaucoma surgery.
• PLGA-S58 shows potential as a safer, non-cytotoxic alternative for managing subconjunctival fibrosis.