Dual-responsive semi-IPN hydrogels based on poly (N-isopropyl acrylamide-co-acrylic acid)/glycyrrhizin cross-linked chitosan for controlled drug release

The development of novel semi-IPN hydrogels composed of a cross-linked chitosan (CC) network and a thermo-responsive linear copolymer, i.e., poly (N-isopropyl acrylamide-co-acrylic acid) [P(NIPAM-co-AA)], with drug release capability in response to both temperature and pH changes has various potential medical applications. The thermo-responsive free copolymer chains inside the CC network were synthesized via free-radical polymerization to prepare the thermal and pH dual-responsive P(NIPAM-co-AA)/CC hydrogels with a semi-IPN structure. The prepared copolymers and semi-IPN hydrogels were characterized by FTIR, TGA, ¹H and ¹³C NMR apparatus, and the LCST transition was determined using UV/Vis spectroscopy. The stronger C-H stretching of the semi-IPN sample at 2920 cm⁻¹ than the CC sample showed that the NIPAM and AA monomers successfully polymerized inside the CC network structure. TGA analysis of the semi-IPN sample exhibited peaks at 249, 379, and 290 °C, corresponding to the presence of the thermo-responsive copolymer composition and the chitosan polymer, respectively. The results showed that depending on the temperature below and above the LCST, the semi-IPN hydrogel exhibited a lower (194%) and higher swelling percentage (413%) because the copolymer chain conformation changed from the coil to globule. The drug release results implied that above the LCST, the hydrogen bond between the gallic acid molecules (GA, drug model) and the semi-IPN structure may be broken, causing a change in drug release in the range of 4.5 − 39.1%. The anti-bacterial test and cytotoxicity of the selected semi-IPN sample were carried out. In an MTT assay, the highest cell viability of the semi-IPN sample with 7.5 mg/ml at 37 °C was 4% more than the control group. The semi-IPN containing GA exhibited anti-bacterial action against the S aureus bacterial strain significantly. This research describes a method to prepare a smart dual-responsive semi-IPN structure with a potential for transdermal applications.