Formulation Development and Pharmacological Evaluation of Curcumin–Resveratrol Co-Loaded Lipid Nanoparticles for Synergistic Protection Against Diabetic Cardiomyopathy in Type 2 Diabetes Mellitus

Abstract

The study focused on the development and evaluation of curcumin–resveratrol co-loaded lipid nanoparticles (CL-LNPs) as a synergistic therapeutic platform for type 2 diabetes–associated cardiomyopathy. The nanoparticles were fabricated using a modified hot-emulsion ultrasonication method and characterized for particle size, polydispersity index, zeta potential, entrapment efficiency, and release behaviour. The optimized CL-LNPs exhibited uniform nanoscale dimensions, low PDI values, and a sufficiently negative zeta potential, indicating excellent colloidal stability. Both curcumin and resveratrol achieved high entrapment within the lipid matrix, and the system demonstrated a sustained-release profile extending up to 48 hours. Antioxidant analyses, including DPPH, ABTS, and nitric oxide assays, revealed markedly enhanced radical-scavenging activity for the co-loaded nanoparticles compared with free curcumin, free resveratrol, and single-drug-loaded formulations. Anti-inflammatory evaluations similarly showed superior inhibition of protein denaturation and improved stabilization of human RBC membranes, confirming enhanced modulation of inflammatory pathways. Cytotoxicity studies on H9c2 cardiomyocytes demonstrated improved cell viability and significantly lower IC₅₀ values for the co-loaded system. Additionally, intracellular ROS quantification and LDH leakage assays confirmed strong cytoprotective and membrane-stabilizing effects, indicating effective attenuation of oxidative and metabolic injury. Overall, the results suggest that curcumin–resveratrol co-loaded lipid nanoparticles offer a highly promising strategy for targeting oxidative stress, inflammation, and cellular damage in diabetic cardiomyopathy. Their synergistic dual-drug efficacy underscores strong potential for further in-vivo exploration and future translational application in diabetes-associated cardiovascular disorders.

Keywords

Co-delivery; Diabetic cardiomyopathy; Lipid nanoparticles; Nanomedicine; Oxidative stress.