Synthesis and characterization of Poloxamer 188-grafted heparin copolymer

Abstract

Background: Poloxamer 188 is a safe biocompatible polymer that can be used in protein drug delivery system. Aim: In this study, a new heparin–poloxamer 188 conjugate (HP) was synthesized and its physicochemical properties were investigated. HP structure was confirmed by Fourier transform infrared spectroscopy (FTIR) and Hydrogen-1 nuclear magnetic resonance spectroscopy (¹H-NMR). Content of the conjugated heparin was analyzed using Toluidine Blue. The critical micelle concentration (CMC) of the copolymer was determined by a fluorescence probe technique. The effect of HP on the gelation of poloxamer 188 was characterized by the rheological properties of the HP–poloxamer hydrogels. Solubility and viscosity of HP were also evaluated compared with poloxamer 188. Results: From the results, the solubility of the conjugated heparin was increased compared with free heparin. The content of heparin in HP copolymer was 62.9%. The CMC of HP and poloxamer 188 were 0.483 and 0.743 mg/mL, respectively. The gelation temperature of 0.4 g/mL HP was 43.5°C, whereas that of the same concentration of poloxamer 188 was 37.3°C. With HP content in poloxamer 188 solution increasing, a V-shape change of gelation temperature was observed. Conclusion: Considering the importance of poloxamer 188 in functional material, HP may prove to be a facile temperature-sensitive material for protein drug-targeted therapy.

Keywords:

• Critical micelle concentration
• heparin
• poloxamer
• synthesis
• temperature sensitive

Acknowledgments

This research is supported by the National Natural Science Fund of China (30870755), Medicine and Health Grant from Wenzhou Bureau of Science and Technology (Y20080098), Zhejiang Province Fund for Talented Youth in Medical Technology (2009QN022), and Zhejiang Province Extremely Key Subject Building Fund ‘Pharmacology and Biochemical Pharmaceutics 2008’.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.