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

Area of Science:

• Ophthalmology
• Biomaterials Science
• Drug Delivery Systems

Background:

• Proliferative vitreoretinopathy (PVR) is a major cause of vision loss due to recurrent retinal detachment.
• Current treatments for PVR have limitations, necessitating novel therapeutic strategies.
• Intravitreal methotrexate (MTX) has shown promise in early clinical studies for PVR management.

Purpose of the Study:

• To develop and characterize a polycaprolactone (PCL)-based drug carrier for sustained release of methotrexate (MTX).
• To evaluate the in vitro pharmacodynamics and biological effects of the MTX-loaded PCL carrier on retinal cells.

Main Methods:

• A PCL-based carrier was fabricated by melting and combining PCL with MTX.
• Drug release kinetics were assessed using an ocular pharmacokinetic model.
• The effects of the MTX-loaded carrier on human retinal pigment epithelium (hRPE) and Müller glial (MIO-M1) cells were evaluated for viability, proliferation, metabolism, migration, protein expression, and toxicity.

Main Results:

• The PCL-MTX carrier demonstrated a sustained release profile of MTX for up to 6 months.
• Exposure to the carrier significantly reduced hRPE and MIO-M1 cell viability and proliferation without inducing toxicity.
• The carrier downregulated fibroblastic protein expression in hRPE cells and affected other protein expressions in proteomics assays.

Conclusions:

• The developed MTX-loaded PCL carrier exhibits a prolonged release profile and potential protective effects against PVR in vitro.
• This novel drug delivery system addresses limitations of current PVR treatments.
• Further research is needed to explore the clinical applicability of this PCL-MTX carrier for PVR.