Lipid nanoformulations as a platform for antihypertensive applications of a ruthenium nitrosyl compound

Nitric oxide (NO) and derivatives play key roles in immunomodulation and blood pressure regulation. Nitrosyl ruthenium complexes are studied as vasorelaxant agents with potential applications in cardiovascular and parasitic diseases. Lipid nanoemulsions enhance their stability and bioavailability. Nanoemulsions were prepared using Pluronic F-127 or Tween 80 as surfactants and oleic acid in the oil phase, incorporating the complex cis-[Ru(bpy)₂(SO₃)(NO)](PF₆) (RuNO). Two optimized formulations were selected: NanoPluNO (Dh = 235.0 nm, PdI = 0.094, ζ = -24.7 mV) and NanoTwNO (Dh = 163.0 nm, PdI = 0.138, ζ = -33.5 mV), both stable for at least 90 days. The nitrosyl complex exhibited prolonged release following the Peppas-Sahlin model, suggesting anomalous mass transport. HSA studies indicated protein conformational changes, possibly linked to protein corona formation. NanoTwNO demonstrated superior vasorelaxant efficacy over free RuNO in isolated aorta from hypertensive (SHR) versus normotensive (WKY) rats. In vivo, NanoTwNO induced significant dose-dependent hypotension (0.06-1.8 mg/kg) in SHR rats, whereas RuNO had only a mild effect. These findings highlight the enhanced therapeutic potential of nanoemulsified RuNO.