Heparin conjugated polymeric micelle for long-term delivery of basic fibroblast growth factor

Heparin conjugated amphiphilic block copolymer, Tetronic-PCL-heparin (TCH), was developed and its polymeric micelles (PMs) were prepared as an injectable vehicle for long-term delivery of bFGF, which is one of the heparin-binding growth factors (HBGF). TCH PMs were fabricated by a single emulsion and solvent evaporation method. The structural properties of TCH were confirmed by (1)H NMR, FT-IR and GPC. The contents of bound heparin were 0.44 micro g/micro g and the heparin activity by APTT assay was 43.6% when compared to free heparin. The critical micelle concentration (CMC) of TCH PMs was approximately 0.11 g/l. The diameter of TC micelle was approximately 25 nm and its size after conjugation of heparin was increased to 114 nm due to the heparin molecules on the shell of the micelle. The bFGF loading amount of TCH PMs was considerably higher than that of TC, caused by specific interactions between heparin and bFGF. In vitro study, bFGF was released from TCH PMs in a controlled manner over 2 months. The results demonstrated that TCH PMs become a novel candidate for the long-term delivery of various growth factors with heparin-binding domain in tissue engineering.