O-Carboxymethyl chitosan-based pH-responsive amphiphilic chitosan derivatives: Characterization, aggregation behavior, and application

Chitosan has attracted much attention in drug delivery, however, carboxymethyl chitosan (CMC)-based self-aggregated nanocarriers are seldom reported. In this paper, two kinds of CMC-based pH-responsive amphiphilic chitosan derivatives, N-2-hydroxylpropyl-3-butyl ether-O-carboxymethyl chitosan (HBCC) and N-2-hydroxylpropyl-3-(2-ethylhexyl glycidyl ether)-O-carboxymethyl chitosan (H2ECC), have been synthesized by the homogeneous reaction. The molecular structures were characterized by FTIR, H-1 NMR and C-13 NMR. The optimum reaction condition was obtained based on the data of H-1 NMR spectrum: reaction time of 4 h, reaction temperature of 80 degrees C and n(epoxy)/n(-NH2) of 3/1, respectively. The XRD patterns showed the crystallinity of HBCC and H2ECC decreased due to the introduction of hydrophobic segments. The thermostability of HBCC and H2ECC was improved for the formation of heat-resistant stereo-complexed structures. The intermolecular hydrophobic interaction hindered the intermolecular mobility by increasing glass transition temperature of ca. 10 degrees C. Both HBCC and H2ECC have very low critical aggregation concentrations (HBCC: 0.66-1.56 g/L, H2ECC: 0.57-1.07 g/L) and moderate aggregate particle size, which is advantageous for utilization as a drug carrier. The curcumin loaded HBCC and H2ECC aggregates showed nontoxicity, meanwhile, HBCC and H2ECC showed good antibacterial activity against Staphylococcus aureus and Escherichia coli. As a result of these two favorable properties, HBCC and H2ECC could be used as curcumin nanocarriers as well as antibacterial agents.