Rapid self-healing carboxymethyl chitosan/hyaluronic acid hydrogels with injectable ability for drug delivery

Abstract

In this study, the quaternized carboxymethyl chitosan (QCMCS), oxidized hyaluronic acid (OHA), 3,3′-dithiobis-(propionohydrazide) (DTP) were used as raw materials for the synthesis of hydrogels with excellent properties as carriers for drug release. The hydrogels were prepared by a simple “one-pot” method without external stimuli on the basis of interactions between formed dynamic covalent bonds (imine bonds, acylhydrazone bonds, disulfide bonds) and hydrogen bonds. The hydrogels had rapid self-healing properties, with a self-healing rate of 96 % after 30 min, as well as good pH responsiveness and excellent cytocompatibility (up to 98 % cell survival). The compressive stress of the hydrogels reached 423 kPa. Moreover, a representative drug (acetylsalicylic acid) demonstrated sustained release in the hydrogels (>72 h). The drug release behaviour was shown to be consistent with the Fick diffusion mechanism by kinetic modelling. Collectively, the findings demonstrate that the QCMCS + OHA + DTP injectable self-healing hydrogels are a potential material for the construction of pH-controlled drug delivery platforms.