Hypertension remains a major global health burden and a leading risk factor for cardiovascular morbidity and mortality. A central mechanism underlying its pathogenesis is endothelial dysfunction characterized by reduced nitric oxide (NO) bioavailability, increased oxidative stress and impaired vasodilation. Although conventional antihypertensive drugs effectively lower blood pressure, they do not directly restore endothelial NO signalling and may cause adverse effects or tolerance with long-term use. Ruthenium nitrosyl complexes have emerged as promising NO donors owing to their chemical stability, tunable coordination chemistry and capacity for controlled NO release under physiological and stimuli-responsive conditions. However, their therapeutic application is limited by poor aqueous solubility, potential instability in biological environments, rapid systemic clearance and lack of selective vascular targeting. Lipid-based nanoformulations, including liposomes, solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsions, provide an effective strategy to overcome these challenges. Encapsulation of ruthenium nitrosyl complexes within lipid nanocarriers enhances solubility, protects against premature degradation, improves pharmacokinetic profiles and enables sustained and controlled NO release. Preclinical studies demonstrate improved endothelial compatibility, enhanced vasorelaxation, prolonged antihypertensive effects and reduced systemic toxicity compared with free complexes. Furthermore, lipid nanoformulations facilitate targeted vascular delivery and minimize rapid NO scavenging, thereby optimizing therapeutic efficiency. Overall, ruthenium nitrosyl–loaded lipid nanoformulations represent a promising next-generation nitric oxide–based nanotherapeutic approach for achieving controlled, sustained and targeted blood pressure management in hypertension.
Edwin et al. (Mon,) studied this question.