Construction and In Vitro Evaluation of a CS-PLGA/pEGFP/HA Ternary Biodegradable Nanocarrier as a Potential Candidate for Intravitreal Ocular Gene Delivery

In this study, we developed a biodegradable CS-PLGA/pEGFP/HA ternary complex for intraocular gene therapy via intravitreal injection. In our system, plasmid-enhanced green fluorescent protein (pEGFP) was chosen as the model plasmid, chitosan (CS) was used to condense the plasmid DNA, poly(lactic-co-glycolic acid) (PLGA) provided sustained-release potential and structural protection for plasmids, and hyaluronic acid (HA) served as a ligand for targeting CD44 receptors on the surface of adult retinal pigment epithelial (ARPE-19) cells. In vitro evaluations revealed that the CS-PLGA/pEGFP/HA group exhibited higher cellular uptake, transfection efficiency, and protein expression levels compared with those of free pEGFP and CS-PLGA/pEGFP groups. Several previous studies have verified the feasibility of intravitreal plasmid delivery. Therefore, this CS-PLGA/pEGFP/HA ternary complex is a promising nonviral vector with the potential to deliver plasmids to ocular tissues and enhance protein expression in target cells.