Targeted nano delivery of p53 DNA and carvedilol for the treatment of dilated cardiomyopathy in a rat model.

Abstract

BACKGROUND: Dilated cardiomyopathy (DCM) is a major contributor to cardiovascular morbidity and mortality, and current therapies lack myocardial specificity, leading to limited efficacy and systemic toxicity. This study explores α-lactalbumin nanoparticles (LANPs) as biocompatible carriers for targeted cardiac delivery of gene and drug therapeutics. METHODS: LANPs were synthesized using the sol-oil method with optimized sonication conditions. Particle morphology and size distribution were characterized using TEM, FE-SEM, and DLS. Cellular uptake studies were conducted with β-adrenergic receptor-blocking assays to assess receptor-mediated internalization. Therapeutic performance of plasmid DNA expressing green fluorescence protein-p53 fusion protein (GFP-p53-DNA)- and carvedilol-loaded (CVD) LANPs was evaluated in a doxorubicin-induced rat model of DCM using ECG analysis, biochemical markers, and histopathology. RESULTS: LANPs exhibited uniform spherical morphology with sizes of 44-77 nm for GFP-p53 DNA-loaded and 55-98 nm for CVD-loaded formulations. LANPs showed enhanced uptake in cardiomyocytes via β-adrenergic receptor-mediated (β-AR) endocytosis. In vivo, LANP-mediated delivery of GFP-p53 DNA and CVD resulted in significant improvement in cardiac electrical function, reduced serum injury markers, and restoration of myocardial architecture compared with soluble formulations. CONCLUSIONS: LANPs offer a promising, biocompatible platform for targeted myocardial delivery of gene and drug therapies and may serve as an effective strategy for treating cardiomyopathy.