Protective effects of cross-linked poly(N-acryloyl glycine) nanoparticles in type 2 diabetes-induced complications: in vivo study.

Chronic hyperglycemia-induced ROS and systemic inflammation can lead to damage to peripheral and cardiac nerves as well as the autonomic nervous system. This damage progresses slowly and occurs over a long period of time. This collective damage to vital organs of the body leads to fatal effects such as cardiac arrest or extreme discomfort to patients, and can cause peripheral infections and neuropathic pain. There are limited therapeutic options available for progressive diabetic peripheral neuropathy (DPN) and diabetic cardiac neuropathy (DCN) limited to blood glucose management. Along this line, in this work we have developed biocompatible poly(N-acryloyl glycine) nanoparticles (pNAG NPs) with a size of 100-350 nm and with a porous structure, which help in reducing inflammation and ROS, and subsequently protect neuronal, liver, pancreas, and cardiac tissues. An in vitro study on MIN 6 cells shows the proliferative effects and cytocompatibility of the pNAG nanoparticles. The therapeutic efficiency of these nanoparticles was validated through a high-fat diet-induced diabetes rat model. Metabolic and functional analyses were performed considering essential organs, and determined the insulin sensitivity, glucose and arginine tolerance. ECG and NCV, along with the role of a few essential inflammatory markers and ROS-indicating enzymes (peroxidase), were assessed and proved the therapeutic response of the pNAG NPs. This work further demonstrates the potential impact of pNAG NPs for the management of type 2 diabetes with reduction of inflammation, improvement of metabolic function, and cardio- and neuroprotective effects. The results show that our pNAG NPs and the therapeutic approach can mitigate major diabetes-induced complications and could be an alternate therapeutic option.