Biodegradable star-shaped polycyclic ester elastomers: Preparation, degradability, protein release, and biocompatibility in vitro

Abstract

Effective local delivery methods for sustained and stable release of protein drugs are urgently needed. Biodegradable elastomers based on star-shaped polycyclic esters have received attention for their drug-loading and drug-release kinetics. However, the long degradation periods resulting from their strong lipophilicity greatly hinder their application. In this study, we synthesized new cross-linked elastomers based on methyl-acrylic-star-poly(ϵ-caprolactone- co-d,l-lactide) cyclic ester and methyl-bi-acrylic-poly(ϵ-caprolactone-b-poly(ethylene glycol)-b-ϵ-caprolactone) with different molecular weights; determined their physical, thermal, and morphological characteristics; and studied their in vitro degradation and release of bovine serum albumin and recombinant human interleukin 2. Elastomer hydrophilicity improved with the introduction of methyl-bi-acrylic-poly(ϵ-caprolactone-b-poly(ethylene glycol)-b-ϵ-caprolactone), and a shorter degradation period (~25 weeks) was achieved. Additionally, the degradation rate could be adjusted by varying the composition of methyl-bi-acrylic-poly(ϵ-caprolactone-b-poly(ethylene glycol)-b-ϵ-caprolactone) to directly influence the degree of swelling, cross-linking density, and sol content of the elastomer. The controlled rate of bovine serum albumin and recombinant human interleukin 2 release increased with a larger degree of swelling, higher sol content, and lower cross-link density of the elastomers. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis showed good biocompatibility. These results suggest that these new elastomers are potential candidates for carrier materials in controlled, implantable delivery systems for protein drugs and other biomedical applications.