Therapeutic Potential of Molsidomine-Loaded Liquid Crystal Nanoparticles for the Treatment and Management of Niacin-Induced Varicose Veins: In Vitro and In Vivo Studies

Abstract

Varicose vein therapy has historically relied significantly on invasive surgical procedures, which frequently resulted in poor compliance among patients. The tendency could stem from the past use of abrasive surgical procedures and a lack of documented drug-induced animal models. To address this challenge, we envisaged an innovative approach for animal model development that uses niacin-induced recurrent flushing. And to further treat the condition, we used liquid crystal nanoparticles (LCNPs) as carriers for the antiangiogenic, cardio protective, and anti-inflammatory drug molsidomine. After the successful initiation of reticular perforant varicose veins, the animals were administered and treated with molsidomine-loaded liquid crystal nanoparticles (MD-LCNPs) that were simultaneously synthesized via a straightforward homogenization method. The preparation of MD-LCNPs involved inducing the disruption of a cubic-phase gel of glyceryl monostearate (GMS) by Milli-Q water in the presence of a Tween-80. Characterization of MD-LCNPs encompassed an assessment of their physicochemical properties. Microscopic studies revealed monodispersity with an average size of 195 ± 55.94 nm. In vitro evaluations demonstrated commendable antioxidant potential, excellent swelling behavior, and sustained release behavior of MD-LCNPs. Furthermore, MD-LCNPs exhibited nontoxicity toward cells, with minimal generation of reactive oxygen species (ROS) or nitric oxide (NO). Histopathological and hematological analysis indicated the efficacy of MD-LCNPs in ameliorating niacin-induced varicose veins, the absence of detrimental and toxic effects on blood cells and visceral organs, and safety for intravenous administration. Following the administration of nanoparticles, the formulation demonstrated appropriate levels of prostaglandins (PGDs), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and vascular endothelial growth factor (VEGF). This substantiates the formulation’s suitability for the treatment and management of varicose veins. In conclusion, our work shows an efficient method that induces varicose veins in rodents, and also a promising nanocarrier-based drug delivery approach using MD-LCNPs for effective and safe varicose vein therapy.