Gamma Irradiation Effects on Molecular Weight and in Vitro Degradation of Poly(D,L-Lactide-CO-Glycolide) Microparticles
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 (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 γ-irradiation on initial molecular weight distribution and onset of mass loss for PLGA, but no effect on rate of mass loss.
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- 1.D. H. Lewis. Controlled Release of Bioactive Agents From Lactide/Glycolide Polymers. In M. Chasin and R. Langer (eds.). Biodegradable Polymers as Drug Delivery Systems, Marcel Dekker Inc., New York. 1990, pp 1–41.Google Scholar
- 2.R. G. Sinclair. Glycolide and Lactide Copolymers for Slow Release of Chemotherapeutic Agents. 5th International Symposium on Controlled Release of Bioactive Materials, Gaithersburg, MD. Aug. 14–16, 1978.Google Scholar
- 3.G. Spenlehauer, M. Vert, J. P. Benoit, F. Chabot, and M. Veillard. Biodegradable Cisplatin Microspheres Prepared by the Solvent Evaporation Method: Morphology and Characteristics. J. Control. Rel. 7:217–229 (1988).Google Scholar
- 4.C. G. Pitt, M. M. Gratzl, A. R. Jeffcoat, R. Zweidinger, and A. Schindler. Sustained Drug Delivery Systems II: Factors Affecting Release Rates From Poly(E-caprolactone) and Related Biodegradable Polyesters. J. Pharm. Sci. 68:1534–1538 (1979).Google Scholar
- 5.Y. Cha, and C. G. Pitt. The Acceleration of Degradation-Controlled Drug Delivery from Polyester Microspheres. J. Control. Rel. 8:259–265 (1989).Google Scholar
- 6.S. Yolles, and M. F. Sartori. Degradable Polymers for Sustained Drug Release. In R. L. Juliano (ed.). Drug Delivery Systems, University Press, London. 1980, p. 84.Google Scholar
- 7.R. Bodmeier, K. H. Oh, and H. Chen. The Effect of the Addition of Low Molecular Weight Poly(D,L-lactide) on Drug Release from Biodegradable Poly(D,L-lactide) Drug Delivery Systems. Int. J. Pharm. 51:1–8 (1989).Google Scholar
- 8.D. K. Gilding, A. M. Reed. Biodegradable Polymers for Use in Surgery-Poly(glycolic)/Poly(lactic acid) Homo-and Copolymers: 1. Polymer. 20:1459–1464 (1979).Google Scholar
- 9.M. C. Gupta, and V. G. Deshmukh. Radiation Effects on Poly(lactic acid). Polymer. 24:827–830 (1983).Google Scholar
- 10.T. R. Tice, D. H. Lewis, R. L. Dunn, W. E. Meyers, R. A. Casper, and D. R. Cowsar. Biodegradation of Microcapsules and Biomedical Devices Prepared with Resorbable Polyesters. Proc. Int. Symp. Control. Rel. Bioact. Mater. 9:21 (1982).Google Scholar
- 11.R. C. Mehta, R. Jeyanthi, S. Calis, B. C. Thanoo, K. W. Burton, and P. P. DeLuca. Biodegradable Microspheres as Depot System for Parenteral Delivery of Peptide Drugs. J. Control. Rel. 29:375–384 (1994).Google Scholar
- 12.W. W. You, J. J. Kirkland, and D. D. Bly. Modern Size Exclusion Chromatography, Wiley-Interscience, New York, 1978.Google Scholar
- 13.J. E. Wilson. Radiation Chemistry of Monomers, Polymers, and Plastics, Marcel Dekker Inc., New York, 1974, p. 374.Google Scholar
- 14.R. W. Baker. Controlled Release of Biolocally Active Agents, Wiley Interscience, New York, 1987, pp. 84–131.Google Scholar
- 15.H. Fukuzaki, M. Yoshida, M. Asano, M. Kumakura, T. Mashimo, H. Yuasa, K. Imai, and H. Yamanaka. In Vivo Characteristics of High Molecular Weight Copoly(L-lactide/glycolide) with S-Type Degradation Pattern for Application in Drug Delivery Systems. Biomaterials. 12:433–437 (1991).Google Scholar
- 16.A. M. Reed, and D. K. Gilding. Biodegradable Polymers for use in Surgery-Poly(glycolic)/Poly(lactic acid) Homo-and Copolymers: 2. In Vitro Degradation. Polymer. 22:494–498 (1981).Google Scholar
- 17.R. A. Kenley, M. O. Lee, T. R. Mahoney II, L. M. Sanders. Poly(lactide-co-glycolide) Decomposition Kinetics In Vivo and In Vitro. Macromolecules. 20:2398–2403 (1987).Google Scholar
- 18.M. Inokuti. Weight-Average and Z-Average Degree of Polymerization for Polymers Undergoing Random Scission. J. Chem. Phys. 38:1174–1178 (1963).Google Scholar