In Vivo Degradation Mechanism and Biocompatibility of a Biodegradable Aliphatic Polycarbonate: Poly(Trimethylene Carbonate-co-5-Hydroxy Trimethylene Carbonate).

Abstract

A recently developed viscous liquid aliphatic polycarbonate, poly(trimethylene carbonate-co-5-hydroxy trimethylene carbonate), has advantageous properties for the delivery of acid-sensitive drugs such as proteins and peptides. This copolymer degrades in vitro via an alkaline-catalyzed intramolecular cyclization reaction yielding oligo (trimethylene carbonate), glycerol, and carbon dioxide, but its in vivo degradation mechanisms are presently unknown. The in vivo degradation mechanism and tissue response to this copolymer were investigated following subcutaneous implantation in Wistar rats. The molecular weight and composition of the copolymer varied in the same manner following subcutaneous implantation as observed in vitro. These findings suggest that the copolymer also degraded in vivo principally via intramolecular cyclization. The tissue response in terms of the inflammatory zone cell density, fibrous capsule thickness, and macrophage response was intermediate to that of two clinically used biodegradable sutures, Vicryl and Monocryl, indicating that the copolymer can be considered biotolerable. Collectively, the data show that further development of this copolymer as a drug delivery material is warranted.