Temperature/pH/reduction-sensitive multiple stimulus-responsive nanogels synthesized by one-pot method for design as curcumin carriers

[Display omitted] •Preparation of monodisperse nanogel by reflux precipitation polymerization.•Nanogel system can be used as slow-release carrier for active drugs.•Curcumin-loaded nanogel system with multiple stimulus-responsive release behaviors.•Curcumin-loaded nanogel system stabilizes antioxidant effects.•Multiple stimulus-responsive nanogel system is biocompatible. Curcumin (Cur) is of interest due to its widely reported pharmacology, which is limited by its low water solubility and low bioavailability of clinical use. Here, we report the characterization and application of a multiple stimulus-responsive nanogel loaded with Cur. Sensitive P(AM-co-NIPAM) nanogels for pH, temperature, and reduction stimuli were prepared by reflux precipitation polymerization method using AM and NIPAM as raw materials. DLS and SEM analyses showed that the fabricated nanogels had a uniform size distribution with spherical and nucleated-shell structures. By adjusting the feeding amounts of reactive monomers, cross-linkers, and initiators, a series of monodisperse nanogels with different particle sizes could be obtained. The representative nanogels have different Cur-loaded behaviors at different temperatures, times, and initial concentrations of the drug, as well as a sensitive release to changes in pH, temperature, or reducing conditions. Cur-P(AM-co-NIPAM) nanogels showed superior antioxidant activity over the free Cur in vitro. Meanwhile, it inhibited LPS and H2O2-induced oxidative stress, which could effectively inhibit the cellular production of excessive reactive oxygen species and had a protective effect against LPS-induced cellular damage. This nanogel controlled release system significantly improved the safety limit of Cur without hemolytic behavior and had good cytocompatibility. The successful development of such Cur nanogels will lead to advanced materials that can be functionalized and optimized for the controlled delivery of small molecules or biomolecules for targeted therapeutic and biomedical applications.