A new dual stimuli responsive hydrogel: Modeling approaches for the prediction of drug loading and release profile

In this study, N-tert-butylmaleimic acid was designed for the first time and synthesized by reaction of maleic anhydride with tert-butylamine and evaluated as a new functional monomer for preparation of new pH-responsive hydrogels. Its structure was verified with FTIR, 1H and 13C NMR. A new pH- and temperature-responsive hydrogel p(TBMAC-co-NIPAM), based on TBMAC and NIPAM, was successfully prepared via free-radical copolymerization technique in an aqueous solution. The chemical and structural properties of the hydrogels were identified by FTIR and SEM. The swelling properties of these hydrogels were systematically investigated according to various parameters such as time, temperature, pH and salt effects, and the results show that they are strongly influenced by the content of TBMAC and exhibit strong pH, temperature and salinity sensitivity. In addition, swelling kinetics and water diffusion mechanisms in hydrogels were discussed. In addition, in vitro drug release studies were performed in simulated gastric, isotonic serum and intestinal fluid at two different temperatures (23 and 37 °C) by taking R6G as a model drug. Drug loading results were investigated with various isotherm models such as Langmuir, Freundlich, Temkin and Dubinin-Radushkevich. Various kinetic models such as zero-order, first-order, Higuchi model and Korsmeyer-Peppas models were applied to determine the drug release mechanism. The results indicated that drug release involves non-Fickian transport mechanism. These results suggest that this new pH- and thermo-responsive hydrogel may be used to improve sustained release of drugs.