Precision nanophytomedicine: Alginate-chitosan nanogels encapsulating Olea ferruginea ethyl acetate fraction for enhanced cardiovascular protection.

Cardiomyocyte death is a primary cause of cardiovascular diseases, including maladaptive cardiac hypertrophy (CH). Oxidative stress from excessive reactive oxygen species (ROS) contributes to cardiomyocyte apoptosis. Due to the limitations associated with conventional antioxidants, plant-derived therapeutics have emerged as promising alternatives. However, their therapeutic potential is often hindered by poor in vivo efficacy. This study enhances the therapeutic efficacy of the ethyl acetate fraction (EAF) of Olea ferruginea (O. ferruginea) leaves by formulating it into an alginate-chitosan nanogel (EAF-AC-NG). EAF-AC-NG, synthesized through an ionic pre-gelation and polyelectrolyte complexation method, demonstrated a small size, high encapsulation efficiency (80 ± 0.886 %), and sustained-release properties. In a rat model of maladaptive CH, EAF-AC-NG significantly reduced ROS, downregulated pro-apoptotic BAX mRNA expression, and enhanced antioxidant enzyme activity compared to free EAF. These effects improved cardiac health indicators and preserved myocardial structure, as confirmed by histological analysis. The findings suggest that EAF-AC-NG is a promising nano-phytomedicine for cardiovascular therapy, offering a targeted approach to mitigating ROS-induced cardiac remodeling. Further preclinical and clinical studies are needed to establish its therapeutic potential.