Synthesis and physicochemical properties of pH-sensitive hydrogel based on carboxymethyl chitosan/2-hydroxyethyl acrylate for transdermal delivery of nobiletin

In this study, CmCHT-g-pHEA hydrogels were prepared by grafting 2-hydroxyethyl acrylate (2-HEA) onto carboxymethyl chitosan (CmCHT) using N, N'-methylenebis(acrylamide) (MBA) as a crosslinker. The physico-chemical properties and in vitro drug release behavior of the CmCHT-g-pHEA hydrogels were studied. The hydrogels were synthesized by radical polymerization, and confirmed by FT-IR, C-13 NMR, and H-1 NMR analysis. The 3D network structure was characterized by scanning electron microscopy observation, and the water binding capacity of the hydrogels was measured by thermogravimetric analysis. The swelling ratio of the hydrogel was evaluated in pH buffer and increased at high pH. In addition, we confirmed that the gel network was stable using rheological analysis. The hydrogel with optimal viscoelasticity and gel fraction was selected, and nobiletin, which is known to be an effective acne treatment, was used as a model drug to test the drug-carrying properties of the gel. The mechanism of the release nobiletin from the CmCHT-g-pHEA hydrogel was verified to be a Fickian diffusion-based mechanism. In in vitro skin permeation experiments, the CmCHT-g-pHEA hydrogel improved the transdermal delivery of nobiletin. In conclusion, the newly synthesized CmCHT-g-pHEA hydrogel has potential applications as a pH-sensitive transdermal drug delivery system.