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

Abstract

In this paper, a novel mono-methacrylated β-cyclodextrin (β-CD) monomer mediated by disulfidebond was synthesized, and then thermal copolymerized with HEMA monomer in the presence ofa little crosslinker to prepare redox-responsive hydrogel for regulated drug delivery. The structureof the monomer was confirmed by FTIR, 1H NMR, 13C NMR spectroscopy. The substitution degree ofpolymerizable methacrylated group grafted onto β-CD was about 1 by calculating by1H NMR(0.987) and element analysis (0.937). The mono-methacrylated β-CD monomer can well copoly-merize with 2-hydroxyethyl methacrylate (HEMA) monomer with gel fraction over 80%. Thehydrogel shows low cytotoxicity, and copolymerization of the mono-methacrylated β-CD mono-mer in the hydrogels increases its equilibrium swelling degree (ESD) and tensile strength, while itstransmittance slightly decreases. Drug loading and release rate are dependent on the β-CDcontent. The hydrogel with high β-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 β-CD sustained drug release, especially CUR release was prolonged more than 24 h from 5 h of purepHEMA 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 ofβ-CD content, the more sensitive the hydrogels to GSH, resulting in rapider drug release rate.