Cyclodextrin-grafted redox-responsive hydrogel mediated by disulfide bridges for regulated drug delivery

In this paper, a novel mono-methacrylated beta-cyclodextrin (beta-CD) monomer mediated by disulfide bond was synthesized, and then thermal copolymerized with HEMA monomer in the presence of a little crosslinker to prepare redox-responsive hydrogel for regulated drug delivery. The structure of the monomer was confirmed by FTIR, 1H NMR, 13C NMR spectroscopy. The substitution degree of polymerizable methacrylated group grafted onto beta-CD was about 1 by calculating by1H NMR (0.987) and element analysis (0.937). The mono-methacrylated beta-CD monomer can well copolymerize with 2-hydroxyethyl methacrylate (HEMA) monomer with gel fraction over 80%. The hydrogel shows low cytotoxicity, and copolymerization of the mono-methacrylated beta-CD monomer in the hydrogels increases its equilibrium swelling degree (ESD) and tensile strength, while its transmittance slightly decreases. Drug loading and release rate are dependent on the beta-CD content. The hydrogel with high beta-CD content of 13.83 wt% shows 1.8 and 8.5 folds puerarin (PUE) and curcumin (CUR) loading than pure pHEMA hydrogel, respectively. The incorporation of beta-CD sustained drug release, especially CUR release was prolonged more than 24 h from 5 h of pure pHEMA hydrogel (80% release). The hydrogels are highly sensitive to reduced glutathione (GSH), and low concentration of GSH of 3 mM can significantly accelerate drug release rate. The higher of beta-CD content, the more sensitive the hydrogels to GSH, resulting in rapider drug release rate.