Polyphenol-based nanoparticles as multifaceted diabetes modulators

Type 2 diabetes is am chronic disease characterized by insulin resistance, which results in extensive metabolic dysfunction and in a large number of chronic complications. Microangiopathy, macrovascular disease, immune dysfunction, and endothelial dysfunction, among many other conditions, are responsible for high morbidity and mortality rates. The wide range of biological properties of natural polyphenols renders these compounds excellent agents for diabetic complications treatment as revealed in the literature. Nevertheless, these beneficial effects are often mitigated by the chemical properties of these molecules, which result in reduced stability, bioavailability, digestion, intestinal absorption, cell uptake, and pH sensitivity, among other features. Herein, an overview of the nanotechnology and delivery systems currently developed to overcome these drawbacks will be presented. In particular, key criteria to be fulfilled by nanosystems for encapsulating polyphenols are highlighted. Strategies to improve polyphenol bioavailability are discussed, and special attention is given to nanoparticle properties influencing cellular uptake, including size, surface charge, and shape, as well as to polymers from both natural and synthetic origin that can enhance the bioactivity and efficacy of delivered polyphenols. The application of smart engineering of polyphenol-loaded nanosystems is a promising tool for the treatment of the wide range of complications observed in diabetes.