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

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.

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.

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.

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.

This in vitro study introduces a new PCL-based sustained-release MTX drug carrier that may help address major limitations of current PVR treatments.