Injectable multifunctional carboxymethyl chitosan/hyaluronic acid hydrogel for drug delivery systems

Abstract

Injectable hydrogels with notable mechanical properties and self-healing ability are promising carriers for use as a drug delivery system. Here, adipic acid dihydrazide (ADH) and calcium ions (Ca2+) were introduced into quaternary ammonium carboxymethyl chitosan and aldehyde-modified hyaluronic acid hydrogels (QCS + OHA). The hydrogels were synthesized through the interaction of the Schiff bases (imine bonds, acylhydrazone bonds) and coordination bonds via a facile one-step approach. The gelation time (∼54 s) ensured excellent injectability. The QCS + OHA + ADH + Ca2+ hydrogel had notable mechanical properties (compressive stress up to 896.30 KPa), good self-healing ability (up to 94 %), good pH responsiveness, and excellent antibacterial properties. In addition, the QCS + OHA + ADH + Ca2+ hydrogel had a high drug loading capacity (121.3 mg/g) and sustained drug release behaviour (≥120 h). The results of cytotoxicity tests showed a high cell proliferation rate (up to 98 %) and good cytocompatibility. In summary, this work presents an injectable and self-healing pH-responsive hydrogel that can be used as a carrier for drug delivery systems.