title: Do iodinated nano-emulsions designed for preclinical vascular imaging alter the vascular reactivity in rat aorta?
abstract: This study proposes a new methodology to evaluate the putative consequences of the long-lasting circulation in the blood pool of nanoparticulate systems widely used in nanomedicine, Indeed, the blood pool contrast agent for micro-computed tomography, i.e. iodinated nano-emulsions, have recently been developed, for their great potential in medical applications such as advanced diagnosis, image-guided surgery, personalized medicine or theragnostics. Stealth nanoparticles exhibit a low recognition by the reticuloendothelial system, resulting in a prolonged circulation in the bloodstream and long-lasting contact with the endothelium. Therefore, the aim of the present study is to determine whether this prolonged interaction could induce an alteration of the vascular reactivity in rat aorta. The Iodinated nano-emulsions were intravenously injected in anesthetized rats. After 1h of contrast agent circulation in the blood pool, the thoracic aorta was removed for the study of vascular reactivity. These animals were compared with control (untreated) rats and a third group of rats receiving an injection of phosphate buffered saline (i.e. dispersing phase of the nano-emulsions). Phenylephrine-induced concentration-dependent contractions of the isolated rat thoracic aorta were not modified whatever the group. Sodium nitroprusside (a nitric oxide (NO) donor)-induced relaxations of endothelium-denuded aorta were also unaltered in response to the different administrations. In contrast, in comparison with control animals, endothelium-dependent NO-mediated relaxations to acetylcholine were significantly impaired in thoracic aorta from PBS-treated rats, but not in animals receiving the iodinated nano-emulsion. In addition, neither isoprenaline-induced nor levcromakalim-induced relaxations were modified in the aorta from the three groups of animals. These findings indicate that even with a long-lasting residence time of the iodinated nano-emulsion in the blood flow, these iodinated nano-emulsions do not alter the vascular reactivity and thus can be used as contrast agent for preclinical vascular imaging on small laboratory animals.
authors.affiliation: UMR 7199 CNRS, Laboratoire de Conception et Application de Molécules Bioactives, équipe de Pharmacie Biogalénique, Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, BP 60024, 67401 Illkirch Cedex, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Anton
authors.forename: Marina
authors.initials: M
authors.lastname: Atzenhoffer
authors.forename: François
authors.initials: F
authors.lastname: Daubeuf
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Valérie B
authors.initials: VB
authors.lastname: Schini-Kerth
authors.forename: Barbara
authors.initials: B
authors.lastname: Delmotte
authors.forename: Thierry F
authors.initials: TF
authors.lastname: Vandamme
authors.forename: Thierry
authors.initials: T
authors.lastname: Chataigneau
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D003287:Contrast Media / Q000008:administration & dosage / Q000494:pharmacology*; D003973:Diatrizoate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004655:Emulsions; D007275:Injections, Intravenous; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles; D051381:Rats; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D055114:X-Ray Microtomography
chemical_list: D003287:Contrast Media; D004655:Emulsions; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D003973:Diatrizoate
keywords: Aorta; Contraction; Nano-emulsion; Nitric oxide; Relaxation