Pharmacokinetics and Toxicity Evaluation of a PLGA and Chitosan-Based Micro-Implant for Sustained Release of Methotrexate in Rabbit Vitreous.

The present research investigates the pharmacokinetics and toxicity of a chitosan (CS) and poly(lactic-co-glycolic) acid (PLGA)-based methotrexate (MTX) intravitreal micro-implant in normal rabbit eyes. PLGA and CS-based micro-implants containing 400 µg of MTX were surgically inserted in the vitreous of twenty-four New Zealand rabbits using minimally invasive procedures. The PLGA-coated CS-MTX micro-implant and the placebo micro-implant were inserted in the right eye and in the left eye, respectively, of each rabbit.

Non-invasive evaluation of toxicity in vitreoretinal domain following insertion of sustained release methotrexate micro-implant.

Purpose: To evaluate the safety and toxicity profile of a chitosan (CS) and poly(lactic-co-glycolic) acid (PLGA)-based sustained release methotrexate (MTX) intravitreal micro-implant in normal rabbit eyes using non-invasive testing that included electroretinography (ERG), ultrasound biomicroscopy (US), slit-lamp biomicroscopy (SLB), funduscopy, and intraocular pressure (IOP).

Methods: PLGA-coated CS-based micro-implants containing 400 μg of MTX and placebo (without drug) micro-implants were surgically-implanted in the vitreous of the right and the left eyes, respectively, in each of the thirty New Zealand rabbits. ERG, US, SLB, funduscopy, and IOP were assessed in both eyes at pre-determined time points (days: 1, 3, 7, 14, 28 and 56).