Gamma irradiation effects on molecular weight and in vitro degradation of poly(D,L-lactide-CO-glycolide) microparticles

Abstract

Purpose: The objective of the reported work was to quantitatively establish gamma-irradiation dose effects on initial molecular weight distributions and in vitro degradation rates of a candidate erodible biopolymeric delivery system.

Methods: Poly(D,L-lactide-coglycolide) (PLGA) porous microparticles were prepared by a phase-separation technique using a 50:50 copolymer with 30,000 nominal molecular weight. The microparticles were subjected to 0, 1.5, 2.5, 3.5, 4.5, and 5.5 Mrad doses of gamma-irradiation and examined by size exclusion chromatography (SEC) to determine molecular weight distributions. The samples were subsequently incubated in vitro at 37 degrees C in pH 7.4 PBS and removed at timed intervals for gravimetric determinations of mass loss and SEC determinations of molecular weight reduction.

Results: Irradiation reduced initial molecular weight distributions as follows (Mn values shown parenthetically for irradiation doses): 0 Mrad (Mn = 25200 Da), 1.5 Mrad (18700 Da), 2.5 Mrad (17800 Da), 3.5 Mrad (13800 Da), 4.5 Mrad (12900 Da), 5.5 Mrad (11300 Da). In vitro degradation showed a lag period prior to zero-order loss of polymer mass. Onset times for mass loss decreased with increasing irradiation dose: 0 Mrad (onset = 3.4 weeks), 1.5 Mrad (2.0 w), 2.5 Mrad (1.5 w), 3.5 Mrad (1.3 w), 4.5 Mrad (1.0 w), 5.5 Mrad (0.8 w). The zero-order mass loss rate was 12%/week, independent of irradiation dose. Onset of erosion corresponded to Mn = 5200 Da, the point where the copolymer becomes appreciably soluble.

Conclusions: The data demonstrated a substantial effect of gamma-irradiation on initial molecular weight distribution and onset of mass loss for PLGA, but no effect on rate of mass loss.