A Polycaprolactone-Based Drug Carrier Loaded With Methotrexate to Attenuate Proliferative Vitreoretinopathy In Vitro

Purpose: Proliferative vitreoretinopathy (PVR) leads to poor outcomes through recurrent detachment. Early clinical evidence suggests that repeated intravitreal injections of methotrexate (MTX) may offer protective benefits. In this study, we developed a polycaprolactone (PCL)-based drug carrier loaded with MTX and examined its in vitro pharmacodynamics and biological effects in vitro. Methods: PCL was melted and combined with MTX to form a solidified carrier, which was then characterized by electron microscopy. Drug release kinetics were assessed using an ocular pharmacokinetic model. Human retinal pigment epithelium (hRPE) cells and Müller glial cells (MIO-M1) were exposed to the MTX-loaded carrier for 48 hours, and proliferation, metabolism, migration, protein expression, and toxicity were evaluated. Results: Ultrastructural analysis confirmed the typical morphology of the PCL-based matrix. The pharmacokinetic model revealed an initial burst release of MTX followed by a sustained release over approximately 6 months. Exposure to the drug carrier significantly reduced viability and proliferation of both hRPE and MIO-M1 cells, while toxicity was not detected. The drug carrier led to downregulation of fibroblastic protein expression in hRPE, but did not affect MIO-M1. Several other proteins exhibited significant regulation in the proteomics assay. Conclusions: The MTX-loaded PCL carrier maintained a prolonged release profile and demonstrated potential protective effects against PVR in vitro. Further studies are warranted to explore the clinical applicability of this drug delivery system. Translational Relevance: This in vitro study introduces a new PCL-based sustained-release MTX drug carrier that may help address major limitations of current PVR treatments.