Synthesis and self-assembly of biomimetic phosphorylcholine-bound chitosan derivatives

Biomimetic N-phosphorylcholine (PC)-chitosan derivatives (PCCs) with a phosphoramide linkage between glucosamine and PC in various degree of substitution (DS) were synthesized through Atherton-Todd reaction and subsequently hydrolysis under the mild conditions, and structurally characterized by H-1 NMR, P-31 NMR, FT-IR and GPC. The incorporation of zwitterionic PC groups modified the hydrophilic/hydrophobic balance of chitosan derivatives to induce the formation of nanosized micelles by self-assembly in neutral aqueous solution. Fluorescence measurements revealed that the critical aggregation concentration (CAC) of PCCs solutions increased with increasing the DS of PC. The physicochemical properties of PCCs aggregates in neutral aqueous solutions were investigated by AFM and dynamic light scattering (DLS). The results confirmed that the amphiphilic PCCs copolymers can self-assemble to form nanosized spherical micelles with zeta potential between 0 and 4 mV, suggesting that the PCCs nano-aggregates were mostly covered with electrically neutral zwitterionic PC groups. Furthermore, all the PCCs samples showed low toxicity against NIH/3T3 cells after incubated for 4 h or 24 h, indicating their safety for biomedical application. (C) 2012 Elsevier Ltd. All rights reserved.