Development of uniform fenofibrate-loaded biodegradable microparticle by membrane emulsification

Abstract

Fenofibrate has shown therapeutic effects on diabetic retinopathy. However, fenofibrate can be rapidly cleared from the eye after a single intravitreal injection. Here, we aim to develop fenofibrate loaded PLGA microparticles (Feno-MP) with high drug loading and sustained in vitro release up to 6 months suitable for intravitreal injection. First, orthogonal array experimental design was applied for formulation optimization. The selected formulation parameters were used to formulate Feno-MP using homogenization method and direct membrane emulsification method. Both methods generated Feno-MP with high drug loading and sustained in vitro drug release more than 140 days. Unlike the polydisperse Feno-MP prepared using homogenization method, membrane emulsification method generated Feno-MP with uniform size distribution. By controlling the membrane pore size, 1.5 µm, 8 µm and 16 µm Feno-MP were formulated and we found that larger Feno-MP demonstrated higher drug loading, more sustained drug release in vitro with less burst drug release than the smaller Feno-MP. In conclusion, we developed Feno-MP with high drug loading and sustained release profile, and elucidated that changing the particle size could have notable impacts on drug loading and release kinetics. Formulating Feno-MP with uniform size distribution by membrane emulsification method would benefit the batch-to-batch repeatability.