The insulin long-acting chitosan - Polyethyleneimine nanoparticles to treat the type 2 diabetes mellitus and prevent the associated complications.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder, which is ultimately treated by the insulin (INS). However, the subcutaneous (s. c.) injection of insulin solution faces the problems of pain and unsatisfactory patient compliance. In this study, the long-acting formulations of insulin are propsed to treat the T2DM and prevent the associated complications. The chitosan (CS) and/or branched polyethyleneimine (bPEI) nanoparticles (bPEI-INS NPs, CS-bPEI-INS NPs) were constructed to load insulin. The long -acting nanoparticles successfully achieved the sustained release of the INS in vitro and in vivo. After s. c. administration, the CS-bPEI-INS NPs greatly improved the INS bioavailability. As a result, the CS-bPEI-INS NPs produced sustained glucose-lowering effects, promising short-term and long-term hypoglycemic efficacy in the T2DM model. Furthermore, the treatment of the CS-bPEI-INS NPs greatly protected the islet in the pancreas and prevented the associated complications of the T2DM, such as cardiac fibrosis in the myocardial interstitium and the perivascular area. In a word, the CS-bPEI-INS NPs was an encouraging long-acting formulation of insulin and had great potential in the treatment of T2DM.