Long-term in vivo degradation behavior of poly(trimethylene carbonate-co-2, 2′-dimethyltrimethylene carbonate)

Abstract

Poly(trimethylene carbonate-co-2, 2′-dimethyltrimethylene carbonate) P(TMC-co-DTC) copolymers with different molecular weights or molar ratios were prepared by bulk ring-opening polymerization (ROP) of trimethylene carbonate (TMC) and 2, 2′-dimethyltrimethylene carbonate (DTC). The in vivo degradation behavior of the resulting copolymers of 2 mm diameter was subsequently investigated by implanting the samples subcutaneously in the back of rats. The data showed that the sample's mass loss was reduced, and the form-stability was enhanced with the increase of DTC segments content in the copolymer while increasing the molecular weight could accelerate the degradation rate and improve the form-stability of the copolymers. Among them, the samples containing 25 mol% DTC segments with a molecular weight of 205 kDa achieved the highest mass loss of 26.1% and maintained good form-stability after 35 weeks of implantation. In particular, implants with high DTC segments amount of 75 mol% (molecular weight of 208 kDa) maintained excellent form-stability and a low mass loss of 4.8% during the implantation cycle and exhibited some properties different from the other groups. Further experimental results showed that the content of DTC segments increased from 74.4% to 77.3%, and the crystallinity of the copolymer transformed to semi-crystalline state also increased from 61.4% to 76.4% during the degradation. The Tg, Tm and hardness of the degraded polymers were correspondingly improved. In addition, the degradation mechanism of surface erosion in vivo of the resulting P(TMC-co-DTC) copolymers were verified. This work provides a promising class of candidate carrier materials for the application of long-acting drug delivery systems through a detailed study of the in vivo degradation behavior of P(TMC-co-DTC) copolymers.