Solution properties of N-(2-allyl-butyl ether)-O-carboxymethyl chitosan and N-(2-allyl-isooctyl...

pH-sensitive and amphiphilic chitosan derivatives can be used as hydrophobic drug carriers, and their rheological properties play a key role in their performance. In this paper, two pH-responsive and amphiphilic chitosan derivatives, N-(2-allyl-butyl glycidyl ether)-O-carboxymethyl chitosan (HBCC) and N-(2-ethylhexyl glycidyl ether)-O-carboxymethyl chitosan (H2ECC) were synthesized, and their rheological properties were studied. The influence of parameters including concentrations of HBCC and H2ECC, the degree of substitution, solution pH, and [Ca²⁺] on the rheological properties were investigated. The results showed that the overlap and entanglement concentration of HBCC and H2ECC was ca. 1.7 wt% and 5 wt%, respectively. The dilute and semidilute solutions showed Newtonian behavior. Above 5 wt%, strong networks formed, and shear-thinning behavior appeared at high shear rates (>10 s^-1) for entangled solutions. A high degree of substitution and pH near the isoelectric points of HBCC and H2ECC corresponded to a low viscosity and viscoelasticity. In addition, Ca²⁺ played a shielding effect on the -COO^- groups at low concentrations (<10 mmol/L), whereas it acted as a cross-linker when [Ca²⁺] ≥ 20 mmol/L. The intermolecular hydrogen bonds were examined by molecular dynamics simulations. The results provide new information related to the application of HBCC and H2ECC for hydrophobic drug packaging and transportation.