Synthesis of biodegradable and functional block copolymers for protein delivery

A poly(ε-caprolactone) oligomer (Mw=3000) (PCL diol) and various hydrophilic polyethers were used to formulate hydroxyl-terminated PCL/polyether triblock copolymers. The copolymers were synthesized by a multi step epoxy-hydroxyl reactions using a bifunctional epoxy compound DENACOL EX 252 as a linking reagent. ¹ H-NMR spectra of the copolymers showed good agreement with the proposed composition. An increase in hydrophilicity with an increasing molar ratio of polyether in the copolymers was observed. Heparin (from porcine intestinal mucosa, 1500 Daltons) was covalently coupled to the copolymers through the terminal hydroxyl groups. The heparin-bounded copolymers showed anti-coagulation activity evaluated by Activated Partially Thrombosis Time (APTT) assay. The feasibility of using the block copolymers for the controlled release of high molecular weight proteins was evaluated using bovine serum albumin (BSA) as a model compound. A higher and more stable release rate of BSA from copolymer films was observed compared to the PCL homopolymer films. In conclusion, a new method to synthesize hydroxy-terminated biodegradable polyester-polyether copolymers was presented. These materials can be made coagulation resistant, and they can be used for controlled delivery of proteins, peptides, and other macromolecules in to the living body