Preparation of PLGA Microspheres Using the Non-Toxic Glycofurol as Polymer Solvent by a Modified Phase Inversion Methodology

Abstract

Poly(D,L-lactide-co-glycolide is a biodegradable copolymer that can release pharmaceuticals. These pharmaceuticals can provide local therapy and also avert the clinical issues that occur when a drug must be given continuously and/or automatically. However, the drawbacks of using poly(D,L-lactide-co-glycolide include the kinetics and duration of time of poly(D,L-lactide-co-glycolide drug release, the denaturing of the drug loaded drug, and the potential clinical side effects. These drawbacks are mainly caused by the volatile organic solvents needed to prepare poly(D,L-lactide-co-glycolide spheres. Using the non-toxic solvent glycofurol solvent instead of volatile organic solvents to construct poly(D,L-lactide-co-glycolide microspheres may deter the issues of using volatile organic solvents. Up to now, preparation of such glycofurol spheres has previously met with limited success. We constructed dexamethasone laden poly(D,L-lactide-co-glycolide microspheres utilizing glycofurol as the solvent within a modified phase inversion methodology. These prepared microspheres have a higher drug load and a lower rate of water diffusion. This prolongs drug release compared to dichloromethane constructed spheres. The glycofurol-generated spheres are also not toxic to target cells as is the case for dichloromethane-constructed spheres. Further, glycofurol-constructed spheres do not denature the dexamethasone molecule and have kinetics of drug release that are more clinically advantageous, including a lower drug burst and a prolonged drug release.