Physically cross-linked pH-responsive chitosan-based hydrogels with enhanced mechanical performance for controlled drug delivery

A novel physically cross-linked pH-responsive hydrogel with enhanced mechanical performance (PCAD) was prepared from chitosan (CS), acrylic acid (AA) and (2-dimethylamino) ethyl methacrylate (DMAEMA) via in situ free radical polymerization for controlled drug delivery. The successful fabrication of the hydrogels was verified by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) measurements. Scanning electron microscopy (SEM) and mechanical analyses demonstrated that the morphological and mechanical behaviors of the resultant hydrogels were strongly affected by the content of AA and DMAEMA. Moreover, the swelling properties of these hydrogels were systematically investigated, and the results indicated that they exhibited strong pH sensitivity. The drug delivery applications of such fabricated hydrogels were further evaluated, from which Bovine serum albumin (BSA) and 5-fluorouracil (5-Fu) were chosen as the model drugs for in vitro release. The results showed that the amount of 5-Fu and BSA released can be tuned by changing the composition of the hydrogel and the pH of the medium. Toxicity assays confirmed that the blank hydrogels had negligible toxicity to normal cells, whereas the 5Fu-loaded hydrogels remained high in cytotoxicity for LO2 and HepG-2 cancer cells. As seen from the results, PCAD hydrogels seem to have a potential application in drug-delivery systems controlled by the external pH value for cancer therapy.