Structure formation in injectable poly(lactide-co-glycolide) depots. II. Nature of the gel.

Abstract

The benzyl benzoate solutions of poly(D,L-lactide-co-glycolide), a random oriented synthesized copolymer with L/G ratio of 50:50, have been shown to form gels during aging and upon injection into buffer or water. The gelation properties influence drug release kinetics for these injectable, depot-forming solutions. In this article, we report on the mechanism of gelation. We find that only polymers that have a certain average block length of glycolide units form gels during aging as well as depots upon in vitro. Thus, gel formation is likely due to the formation of ordered solvated aggregates of blocky glycolide units. Rheometry, differential scanning calorimetry, and nuclear magnetic resonance were used to investigate the gelation kinetics and the polymer molecular parameters. Of all the polymers used, poly(lactide-co-glycolide)s with glycolide average block length <2.9 did not show any gelation behavior. The details of the gelation process are also solvent dependent.