Smart Nano-Insulin Delivery Systems: Possible Route Toward Safer and Physiological Glycemic Control

Abstract

Diabetes mellitus is still a formidable chronic metabolic disease because of the fact that glycemic levels are always out of control, patient compliance is often poor and conventional subcutaneous insulin treatment cannot achieve the physiological insulin release. In the last few years, nano technology has become a promising platform to improve insulin delivery and insulin stability, insulin bioavailability, controlled release, and targeting insulin to specific tissues. The present review will focus on the recent developments of nano-insulin delivery systems such as polymeric nanoparticles, lipid based nanocarriers, inorganic nanoparticles, hybrid nanocomposites and glucose-responsive smart nanosystems. Of these, glucose-responsive nanoparticles are a very promising approach, as they can release insulin in response to blood glucose, in turn providing the potential of self-regulated and more physiologically relevant glycemic control. Additionally, targeted nanoparticles and antioxidant-loaded systems provide new opportunities for pancreatic β-cell protection and reduced systemic toxicity. Despite these promising advances, there are significant challenges to clinical translation, such as long-term toxicity, immunogenicity, lack of reproducibility, scalability, storage instability, regulatory uncertainty, and mixed patient response. For future progress to be made, it is essential that future nanosystems are biodegradable, biocompatible and patient-specific, embedded into digital health technologies, artificial intelligence and closed loop insulin delivery platforms. In conclusion, the use of nanotechnology for insulin delivery shows promising potential to revolutionize the treatment of diabetes, but further studies are needed to ensure its safe integration into everyday clinical use, including extensive preclinical testing, standardized testing protocols, and extensive clinical trials.