Poly(N-isopropylacrylamide) hydrogels cross-linked by α,α-trehalose diacetals as thermo-responsive and acid-degradable carriers for drug delivery

A series of novel thermo-responsive hydrogels cross-linked by acid-degradable trehalose diacetals with VPTTs tailored to biologically useful temperatures were obtained by copolymerization of Nisopropylacrylamide with more hydrophilic comonomers: acrylamide, N-(2-hydroxyethyl)acrylamide or N,N-dimethylacrylamide. Due to the properties of the acetal bond, these hydrogels degraded via acid-catalyzed hydrolysis, in the course of which water-soluble terpolymers were formed and trehalose molecules with bioprotective properties were released. The incorporation of hydrophilic comonomers influenced the volume phase transition, swelling capacity, response rate to temperature change, mechanical properties, morphology and the degradation rate in acidic conditions. The release profile of the model drug, propranolol hydrochloride, was found to be dependent on the hydrogel composition, matrix form, and a medium pH. The preliminarily results of cytotoxicity assay suggest, that hydrogels and terpolymers are non-toxic towards L929 mouse fibroblasts.