Metal-organic framework-based injectable in situ gel for multi-responsive insulin delivery

In this study, an in situ gel with multi-responsiveness was developed for type 1 diabetes mellitus (T1DM). [email protected] was prepared by the “one-pot” method, and it was characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD) and transmission electron microscopy (TEM), and the in vitro studies and TEM image showed that [email protected] had pH-sensitive property. Glucose oxidase (GOx) acted as a glucose-sensitive switch and generated gluconic acid to reduce the pH of the local microenvironment, inducing the destruction of the crystal structure of ZIF-8 and the release of insulin. [email protected] /GOx-Gel was prepared with poloxamer 407 (P407) and poloxamer 188 (P188) as the main hydrogel matrix and HPMC as an excipient. The phase transition would occur to make the gel change from liquid to semi-solid state when in situ gel solution was injected into the body, prolonging drug release time by the erosion and degradation of the gel. During the research process, the gelation temperature, gelation time, injectability, in vitro degradation and morphological feature of [email protected] /GOx-Gel were measured. The in vitro studies showed that [email protected] /GOx-Gel had glucose-sensitive properties, at the same time, the results of the in vivo studies showed that the time for stabilizing normoglycemia of [email protected] /GOx-Gel was 3.5 times that of insulin solution. In a word, the insulin delivery system provided a new strategy for self-regulation treatment of diabetes.