Enhancing the properties of poly(N-isopropylacrylamide) hydrogels through interpenetrating polymer networks with chitosan: a review

Poly(N-isopropylacrylamide) (PNIPAM) is a widely studied thermoresponsive hydrogel which has great potential in controlled drug delivery due to its volume-phase transition near physiological temperature. However, its application is limited by poor mechanical strength, slow response kinetics, and lack of multi-stimuli responsiveness. This review discusses the enhancement of PNIPAM properties through the formation of interpenetrating polymer networks (IPNs) with chitosan, a biocompatible and pH-sensitive natural polymer. Integrating chitosan into PNIPAM-based hydrogels yields IPNs with improved structural stability, higher drug-loading capacity, and multi-responsive behavior. Chitosan introduces pH sensitivity and binding sites, while the interpenetrating architecture reinforces mechanical integrity and tunes diffusion. These systems enable sustained and controlled drug release over 8–12 h under simulated physiological conditions, with release profiles tunable via crosslinking density and environmental stimuli. Despite challenges in reproducibility, crosslinker toxicity, and long-term stability, chitosan–PNIPAM IPNs are promising for advanced drug delivery in multi-stimuli environments such as the gastrointestinal tract or tumor tissues.