Click synthesis of the thermo- and pH-sensitive hydrogels containing β-cyclodextrins

Abstract

Novel intelligent hydrogels containing β-cyclodextrins were prepared by tandem physical and chemical crosslinking method based on Diels–Alder reaction. First, dienophile-functionalized cyclodextrins (HCD–AMI) were synthesized by the coupling reaction of hydroxyethyl-β-cyclodextrins and N-maleoyl alanine (AMI); diene-functionalized polymers (PFMIPA) were synthesized by free radical copolymerization of N-isopropylacrylamide and furfuryl amine maleic acid monoamide, a novel monomer synthesized in our lab. Then, the LCSTs of the PFMIPA were estimated by transmittance measurements of copolymer solutions. After the as-synthesized PFMIPA and HCD–AMI were dissolved separately in water and mixed, the hydrogels with physical crosslinks formed quickly within 10 s at 37 °C. Subsequently, chemical crosslinks came into being gradually due to Diels–Alder reaction. Therefore, there are both physical crosslinks and chemical crosslinks in as-prepared hydrogels, resulting in the improvement of the mechanical strength of the hydrogels. And the in vitro degradation behaviors of the resultant hydrogels were given a pilot study. A general gravimetric method was used to study the swelling behavior of the hydrogels. It was found that the hydrogels showed good pH/temperature-sensitivity. The strategy described here has several advantages for preparing intelligent hydrogels including tunable gelation rate, mild reaction conditions, no initiator or catalyzer, and no organic solvent. We believe that this novel, potentially biocompatible hydrogels could have biomedical applications, especially in the area of tissue engineering and drug-controlled release carriers.