7-nitroindazol-loaded nanoemulsions: Preparation, characterization and its improved inhibitory effect on nitric oxide...

Nitric oxide (NO) participates in several physiological processes such as maintenance of blood pressure, host defense, neurotransmission, inhibition of platelet aggregation and learning and memory. NO is also involved in several diseases or dysfunctions in the cardiovascular, central nervous and musculoskeletal systems. NO also has been shown to be a major player in sepsis. NOS-1-derived NO has been shown to be a relevant species in physiology but also is an important element in pathology. There exist some NOS-1 inhibitors and among of them, 7-nitroindazole has been used for its in vivo selectivity. However, 7-NI has a very short half-life (∼2 h) and a poor water solubility. In this study, we describe the preparation and characterization of 7-NI-loaded nanoemulsions (NE_7-NI). The chemical stability of 7-NI was greatly increased and the drug release rate could be controlled after nanoemulsification. NE_7-NI reduced NO production in a long-lasting manner in vascular smooth muscle cells and skeletal muscle, without cytotoxicity. Our results evidenced that nanoemulsification approach increases the effective action time of 7-NI, rendering a suitable dosage form, which may be an interesting tool to study the role of NOS-1 in physiology and disease.