Folate-decorated polymeric nanoparticles offer a novel approach to deliver poorly soluble drug molecules to retinal pigment epithelium (RPE) while prolonging the therapeutic effects in the posterior segment of the eye. RPE is a monolayer of epithelial cells that forms the outer blood-retinal barrier in the posterior segment of the eye, and is also implicated in the pathology of ocular diseases, such as neovascularization in age-related macular degeneration (AMD). In this study, folate-functionalized poly(ethylene glycol)-b-polycaprolactone (folate-PEG-b-PCL) were synthesized for assembling into nanoparticles of ~ 130 nm. These nanoparticles were internalized into ARPE-19 (human RPE cell line) via receptor-mediated endocytosis, and the cellular uptake was significantly higher than parti...[ Read more ]

Folate-decorated polymeric nanoparticles offer a novel approach to deliver poorly soluble drug molecules to retinal pigment epithelium (RPE) while prolonging the therapeutic effects in the posterior segment of the eye. RPE is a monolayer of epithelial cells that forms the outer blood-retinal barrier in the posterior segment of the eye, and is also implicated in the pathology of ocular diseases, such as neovascularization in age-related macular degeneration (AMD). In this study, folate-functionalized poly(ethylene glycol)-b-polycaprolactone (folate-PEG-b-PCL) were synthesized for assembling into nanoparticles of ~ 130 nm. These nanoparticles were internalized into ARPE-19 (human RPE cell line) via receptor-mediated endocytosis, and the cellular uptake was significantly higher than particles without folate modification. Triamcinolone acetonide (TA) was efficiently encapsulated (>97%) into the folate-decorated nanoparticles and was slowly released over a period of 4 weeks at pH 5.5 and 8 weeks at pH 7.4. The enhanced uptake and controlled release resulted in prolonged anti-angiogenesis effects in RPE cells. In cell culture, the down-regulation of vascular endothelial growth factor (VEGF) and up-regulation of pigment epithelium derived factor (PEDF) lasted for at least 3 weeks, as detected by RT-PCR. Unlike benzyl alcohol, the surfactant found in commercial formulation, the folate-modified nanoparticles were non-toxic. Furthermore, TA became less cytotoxic by being encapsulated in the nanoparticles. Our findings suggest that folate-decorated nanoparticles are promising RPE-targeting drug carriers for intravitreal injection.