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 γ-irradiation dose effects on initial molecular weight distributions and in vitro degradation rates of a candidate credible biopolymeric delivery system.

Methods. Poly(D,L-lactide-co-glycolide) (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 γ-irradiation and examined by size exclusion chromatography (SEC) to determine molecular weight distributions. The samples were subsequently incubated in vitro at 37°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 (M_n values shown parenthetically for irradiation doses): 0 Mrad (M_n = 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 M_n = 5200 Da, the point where the copolymer becomes appreciably soluble.

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