PEG-L-PAF and PEG-D-PAF: Comparative study on thermogellation and biodegradation

Abstract

L-Polypeptides and D-polypeptides can be prepared from natural L-amino acids and non-natural d-amino acids, respectively. In this study, poly(ethylene glycol)-poly(L-alanine-co-L-phenyl alanine) (PEG-L-PAF) and poly(ethylene glycol)-poly(D-alanine-co-D-phenyl alanine) (PEG-D-PAF) with similar molecular weight and composition, but different stereochemistry were investigated, focusing on thermogelling behavior and biodegradation. The sol-to-gel transition temperature of both PEG-L-PAF and PEG-D-PAF aqueous solutions decreased from 26 to 7 °C as the concentration increased from 4.0 wt % to 9.0 wt %. Dynamic light scattering, transmission electron microscopy, circular dichroism spectra, and 13C NMR spectra suggested that the sol-to-gel transition involved changes in molecular assemblies resulting from dehydration of PEG for both PEG-L-PAF and PEG-D-PAF. In particular, the significant differences between PEG-L-PAF and PEG-D-PAF were observed for histocompatibility as well as in vitro/in vivo degradation. Only PEG-L-PAF was significantly degraded by cathepsin B and elastase, as well as under in vivo conditions. The histocompatibility assayed by the H&E staining method showed that formation of the collagen capsule around the PEG-D-PAF gel was thicker than the PEG-L-PAF gel, indicating that acute inflammation was milder with PEG-L-PAF gel than with PEG-D-PAF gel. Current study emphasizes the significance of stereochemistry in biomaterial development. © 2012 American Chemical Society.