Synthesis and characterization of heparin conjugated Tetronic®–PCL copolymer for protein drug delivery

Abstract

Amphiphilic multiblock Tetronic ® –PCL copolymer was synthesized by a ring-opening polymerization of ε-caprolactone with Tetronic ® by using stannous octoate as a catalyst, and Tetronic ® –PCL–heparin conjugate was prepared by coupling heparin with Tetronic ® –PCL copolymer by using EDC/NHS as coupling agents. The physicochemical properties of these polymers were examined by 1 H NMR, FT-IR and GPC. The content of bound heparin is measured to be 0.44 μg/μg and the heparin activity measured by APTT assay is shown to be 43.6% as compared to free heparin. To estimate the feasibility as a polymeric vehicle of this copolymer for protein delivery, the critical micelle concentration (CMC) of the copolymer resulted from self-assembly under aqueous condition was determined by a fluorescence probe technique using pyrene. The diameter of Tetronic ® –PCL micelle in number-averaged scale was observed to be around 25 nm and its size after heparin coupling was increased to 224 nm due to the heparin chain located on the hydrophilic shell of the micelle. Therefore, we suggest that Tetronic ® –PCL–heparin micelle can be a good candidate for the sustained delivery of various proteins with heparin-binding domain in pharmaceutical fields.