New insights into the hydrolytic degradation of poly(lactic acid): participation of the alcohol terminus

The hydrolytic degradation of aliphatic polyesters derived from lactic and glycolic acids (PLA/GA polymers) has been previously shown to proceed heterogeneously in the case of large size devices, the rate of degradation being greater inside than at the surface. A qualitative model based on diffusion-reaction phenomena was proposed which accounts for the formation of the more stable outer layer. However, this model also suggested that devices with dimensions smaller than the thickness of the outer layer should degrade less rapidly than larger ones. In an attempt to check this hypothesis, 15 x 10 x 2 mm compression moulded plates, millimetric beads and submillimetric microspheres and cast films, derived from the same batch of poly (DL-lactic acid) polymer were allowed to age comparatively in isoosmolar 0.13 M phosphate buffer, pH 7.4, at 37 degrees C. Ageing of the various devices was monitored by measuring water absorption, weight loss, L-lactic acid formation, pH and molar mass changes. As expected, large size plates and millimetric beads degraded heterogeneously and much faster than homogeneously degraded submillimetric films and particles.

The in vitro degradation behaviour of a wide range of poly(D,L-lactic-co-glycolic acid) (PLGA) has been examined in terms of degree of degradation and morphological change during an incubation period of up to 53 d. Gel permeation chromatography and differential scanning calorimetry were employed to characterize their degradation profiles. It was found that amorphous PLGA exhibited a transient multiple crystallization behaviour of D- or L-lactic acid oligomers during degradation. This indicated that the hydrolytic scission of ester bonds tends to primarily target the linkage between glycolic acid and D- or L-lactic acid or glycolic acid. In addition, two distinctive glass transition temperatures appeared when these crystallization phenomena occurred, suggesting the transient presence of fast and slowly eroding polymer domains within microspheres during the degradation. This study supports the heterogeneous bulk degradation for PLGA microspheres which has been proposed recently for a large specimen.