Reduction in Burst Release from Poly(D,L-Lactide-Co-Glycolide) Microparticles by Solvent Treatment

Abstract

A high initial burst release of an antisense oligonucleotides drug from poly(lactide-co-glycolide) (PLGA) microparticles prepared by the multiple emulsion (w/o/w) method was significantly reduced, when the microparticles were treated with a polymer non-solvent (ethanol)/water mixture. The ethanol/water mixture acted like a plasticizer and significantly decreased the glass transition temperature (Tg) of the PLGA. Thus, PLGA microparticles in the wet state became soft, and the surface pores were fused together during treatment. As a result, microparticles with reduced surface pores that released a low initial burst were obtained. The reduction in the initial burst was more significant for the smaller microparticles ( < 50 μm) and decreased with increasing microparticle size. A less significant reduction in the initial burst was observed when the microparticles were treated with a polymer solvent (e.g., acetone)/water mixture. Keywords: Microparticles, Initial burst, Poly(lactide-co-glycolide), Glass transition temperature, Solvent treatment, PLGA, probe sonication, Shaker, UV-spectrophotometry, PC UV-Vis scanning spectropho-tometer, Scanning Electron Microscopy, SEM, Differential Scanning Calorimetry, DSC, Scanning electron micrographs, polymer matrix, ethyl acetate, methylene chloride, 2-pyrrolidone