Preparation of thermo/redox/pH‐stimulative poly(N‐isopropylacrylamide‐co‐N,N′‐dimethylaminoethyl methacrylate) nanogels and their DOX release behaviors

Abstract Stimuli‐sensitive drug delivery systems show beneficial features of both medical and pharmaceutical fields. In this article, polymeric nanogel P ( N ‐isopropylacrylamide– N , N ′‐dimethylaminoethyl methacrylate [NIPAM–DMAEMA]) (PND) with pH/redox/thermo‐responsivenesses was synthesized by the in situ polymerization of NIPAM and DMAEMA for the controlled release of doxorubicin hydrochloride (DOX) and N , N ′‐bis(acryloyl)cystamine (BAC) and N , N ′‐methylenebisacrylamide (MBA) act as the crosslinkers, respectively. The structure, size, and zeta potential of PND‐BAC and PND‐MBA were further characterized. Moreover, after loading DOX, the encapsulation efficiency and the in vitro release behavior of PND‐BAC/DOX and PND‐MBA/DOX nanogels were discussed in detail. Compared to PND‐MBA NGs, PND‐BAC nanogels have redox degradability due to the presence of the crosslinker BAC. After loading DOX, the PND‐BAC/DOX nanogel showed a higher encapsulation efficiency (81.6 ± 1.2)% and thermo‐ and pH‐responsiveness as well as redox‐responsive in vitro release. These properties together with excellent environmentally sensitive properties make PND‐BAC as an attractive candidate for application in drug nanocarriers for the targeted drug delivery of model payloads. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1195–1203, 2019.