Biocompatible polymeric nanocomplexes as an intracellular stimuli-sensitive prodrug for type-2 diabetes combination therapy

摘要: Combination therapy is usually considered as a promising strategy owing to its advantages such reduced doses, minimized side effects and improved therapeutic efficiency in variety of diseases including diabetes. Here we synthesized new highly intracellular stimuli-sensitive chitosan-graft-metformin (CS-MET) prodrug by imine reaction between oxidative chitosan metformin for type 2 diabetes (T2D) therapy. Hypothetically, CS-MET functions dually an anti-diabetes well gene delivery vector without superfluous materials. formed nanocomplexes with through electrostatic interactions entered cells Organic Cation Transporter (OCT)-independent endocytosis. The incorporation into has been found increase endosomal escape via the proton sponge effect. When carrying short-hairpin RNA (shRNA) silencing sterol regulatory element-binding protein (SREBP), major transcription factor involved de novo lipogenisis, it SREBP mRNA proteins efficiently. Furthermore, intraperitoneal injection, CS-MET/shSREBP effectively knocked down livers western-type diet (WD)-induced obese C57BL/6J mice, markedly reversed insulin resistance alleviated fatty liver phenotype obvious toxic effects. Thus were able show that renders potential platform activity synergistic enhancement