A polyion complex micelle with heparin for growth factor delivery and uptake into cells

Cationic polymers are promising materials for the controlled delivery of heparin allowing the therapeutic delivery of growth factors bound to heparin. In this study, a series of block copolymers were prepared from oligo(ethylene glycol) methyl ether methacrylate (OEGMEMA) and 2-(methacryloyloxy)ethyl trimethyl ammonium chloride (METEA) via reversible addition-fragmentation chain transfer (RAFT) polymerization by varying the cationic block (METEA) from 5 to 54 units. Polyion complexes micelles between these block copolymers and heparin were formed. Their size could be systematically varied between 5 and 55 nm in size as well as -20 to +10 mV in overall charge by changing the cationic block length as well as the ratio of polymer to heparin. The polymer/heparin complexes did not impair the proliferation of human colon carcinoma cell line, WiDr, compared to cells exposed to medium only. The size of the cationic block copolymer as well as the ratio in which it was complexed with heparin influenced both heparin biological activity in a BaF32 cell assay as well as uptake into WiDr cells as determined by flow cytometry which demonstrated that the properties of the block copolymers can be tuned for various applications.