Novel pH-sensitive chitosan-based hydrogel for encapsulating poorly water-soluble drugs

Carboxymethyl–hexanoyl chitosan (CHC) is an amphiphilic chitosan derivative with excellent swelling ability and water solubility under natural conditions. In this work, the influence of the degree of carboxymethyl and hexanoyl substitution on the pH-sensitive swelling behavior, drug release behavior, and antiadhesion behavior of CHC hydrogels (cross-linked with genipin) were studied. It was found that the pH sensitivity was more pronounced in CHC than in N,O-carboxymethyl chitosan because the hexanoyl group altered the state of water in CHC by inhibiting intermolecular hydrogen bonding. In addition, greater pH sensitivity was observed in samples bearing longer hydrophobic chains (carboxymethyl–palmityl chitosan). Interestingly, when used with ibuprofen (a poorly water-soluble therapeutic agent used here as a model drug), the bursting release of the drug was less prominent in the CHC samples having a high degree of carboxymethyl substitution. The CHC hydrogel also demonstrated good cell compatibility and its antiadhesive ability after grafting was altered by changes in the degree of hexanoyl substitution.