QUERCETIN-LOADED POLYMERIC NANOPARTICLES FOR ENHANCED GLUCOSE UPTAKE AND METABOLIC REGULATION VIA AMPK PATHWAY ACTIVATION

Abstract

Quercetin, a naturally occurring flavonoid, has demonstrated significant potential in the management of metabolic disorders, particularly type 2 diabetes mellitus, due to its antioxidant, anti-inflammatory, and glucose regulating properties. However, its clinical application is limited by poor aqueous solubility, low bioavailability, and rapid metabolic degradation. The present study focuses on the development and evaluation of quercetin loaded polymeric nanoparticles as an advanced drug delivery system to enhance its therapeutic efficacy. The nanoparticles were successfully prepared and characterized for physicochemical properties, drug release profile, and biological activity. In vitro studies revealed a sustained biphasic drug release pattern, improved cellular uptake, and enhanced glucose uptake in treated cells. Mechanistic investigations demonstrated that quercetin loaded nanoparticles significantly activated the AMP-activated protein kinase (AMPK) pathway, leading to increased phosphorylation of AMPK and enhanced GLUT4 translocation. Additionally, modulation of insulin signaling pathways via IRS-1 and PI3K/Akt activation contributed to improved insulin sensitivity. The nanoparticle formulation also effectively reduced oxidative stress and inflammatory markers, including reactive oxygen species, TNF-α, and IL-6, thereby restoring cellular metabolic balance. These findings are consistent with previous studies highlighting the role of quercetin in AMPK-mediated glucose regulation and nanoparticle based drug delivery enhancement. Overall, the study demonstrates that quercetin-loaded polymeric nanoparticles offer a promising nanotherapeutic strategy for improving glucose metabolism and managing metabolic disorders.