Ex Vivo Evaluation of Poly(Solketal Acrylate) Nanoparticles for Intravitreal Drug Delivery to the Posterior Eye Segment

Owing the complex anatomy and multiple physiological barriers, delivering drugs to the posterior segment of the eye remains challenging. While intravitreal injection can improve drug delivery, the diffusion of therapeutics through the vitreous humor and their uptake by the retina remain limited due to the anionic nature of the vitreous humor, attributed to its collagen and glycosaminoglycan content. Poly(solketal acrylate)-based nanoparticles (PSA-NPs) were developed via single-emulsion solvent evaporation and nanoprecipitation techniques and loaded with Nile red (NR-PSA-NPs) as a hydrophobic drug model, enabling in vitro and ex vivo tracking via fluorescence microscopy. These NPs exhibit a neutral to negative surface charge, enhancing their distribution through the vitreous humor. Evaluating these NPs for drug delivery, cytotoxicity studies using retinal cells confirmed their excellent nontoxic profiles. Additionally, fluorescence microscopy and FACS analysis revealed a significant increase in the uptake of NR-PSA-NPs in ARPE-19 cells (human retinal pigment epithelial cell line) compared to that of free dye. Moreover, incubation of NR-PSA-NPs with retinal organ cultures and their intravitreal injection into whole porcine eyes showed red fluorescence across all retinal layers, confirming successful uptake, distribution, and widespread retinal penetration, making these NPs promising carriers for delivering hydrophobic drugs to the posterior eye segment.