Effect of Comonomer Sequence Distribution on the Glass Transition Temperature of Poly(D,L-lactic-co-glycolic acid)

We developed a facile method (named “feed rate-controlled polymerization (FRCP)”) for producing statistically monomer sequence-controlled aliphatic copolyesters, such as uniform poly(lactic-co-glycolic acid) (PLGA). Using this FRCP method, monodisperse PLGA homopolymers having an identical molecular weight with varying degrees of monomer (lactide (LA) and glycolide (GL)) sequence uniformity (uniform vs. gradient PLGA) at various different monomer compositions (LA/GL ratios) were prepared and used to investigate the effect of LA/GL sequence distribution on the glass transition properties of PLGA polymers. The T_g vs. copolymer composition plot showed a significant negative deviation (< ~ 8 K) from the Flory-Fox prediction, indicating a repulsive interaction between the LA and GL monomers. We found that experimental trends between T_g and measures of monomer sequence lengths (monomer triad distribution and composition) quantitatively agree with the predictions of both the Johnston theory (based on the free volume concept) and the Barton theory (based on the configurational entropy concept) with no adjustable parameters. We will also discuss how loaded drugs having asymmetric affinities for LA and GL impact the T_g properties of uniform and gradient PLGA materials.