Metformin-loaded nanoparticles reduce hyperglycemia-associated oxidative stress and induce eNOS phosphorylation in vascular endothelial cells

Abstract

Diabetes mellitus is a chronic disease characterized by metabolic defects, including insulin deficiency and resistance. Individuals with diabetes are at increased risk of developing cardiovascular complications, such as atherosclerosis, coronary artery disease, and hypertension. Conventional treatment methods, though effective, are often challenging, costly, and may lead to systemic side effects. This study explores the potential of nanomedicine applications, specifically Metal-Organic Frameworks (MOFs), as drug carriers to overcome these limitations. The Materials Institute Lavoisier-89 nanoparticles (nanoMIL-89) have previously demonstrated promise as a drug delivery vehicle for chronic diseases due to their anti-oxidant and cardio-protective properties. In this investigation, nanoMIL-89 was loaded with the anti-diabetic drug metformin (MET), creating MET@nanoMIL-89 formulation. We examined the drug release kinetics of MET@nanoMIL-89 over 96 h and assessed its impact on the viability of various endothelial cells. Furthermore, we investigated the nanoformulation effect on the inflammatory marker CXCL8 in these cells and explored its influence on phosphorylated eNOS, total eNOS, and AKT levels. Our findings indicate that nanoMIL-89 effectively released metformin over 96 h and caused a concentration-dependent reduction in CXCL8 release from endothelial cells. Notably, MET@nanoMIL-89 reduced dihydroethidium levels and increased phosphorylated eNOS, total eNOS, and AKT levels. Our results underscore the potential of nanoMIL-89 as a versatile potential drug delivery platform for anti-diabetic drugs, offering a prospective therapeutic approach for diabetic patients with associated cardiovascular complications.