Biodegradation of Poly(α-amino acid) in vitro

Abstract

The preparation of copolypeptides consisting of L-glutamic acid and N-hydroxyalkyl-L-glutamine, or hydrophobic L-amino acids such as L-alanine, L-leucine, or L-valine, was performed to determine the effects of copolymer composition and sequential distributions on the rate of degradation by papain in a PECF at pH=7.4 and 37°C to simulate in vivo polymer degradation. Random copolymers consisting of γ-BLG and γ-MLG, L-ala, L-leu, or L-val were synthesized by the NCA method. Hydrophilic copolymers were obtained by successive reactions of side chains by anhydrous HBr or aminoalcohol treatment. All the samples were found to be extensively degraded by random-chain fracture with papain. Further, the degradation data for these samples followed the Michaelis-Menten rate law, being of the first order in papain concentration. The nature of side chains are important to the rate of degradation by papain and the uncharged side chains of copolymer samples give values much higher than the negatively charged side chain of L-glutamic acid at pH=7.4. The order of the rate of degradation among the former group was: L-ala > L-leu > L-val > N-hydroxyalkyl-L-glutamine.