title: A New NO-Releasing Nanoformulation for the Treatment of Pulmonary Arterial Hypertension.
abstract: Pulmonary arterial hypertension (PAH) is a chronic and progressive disease which continues to carry an unacceptably high mortality and morbidity. The nitric oxide (NO) pathway has been implicated in the pathophysiology and progression of the disease. Its extremely short half-life and systemic effects have hampered the clinical use of NO in PAH. In an attempt to circumvent these major limitations, we have developed a new NO-nanomedicine formulation. The formulation was based on hydrogel-like polymeric composite NO-releasing nanoparticles (NO-RP). The kinetics of NO release from the NO-RP showed a peak at about 120 min followed by a sustained release for over 8 h. The NO-RP did not affect the viability or inflammation responses of endothelial cells. The NO-RP produced concentration-dependent relaxations of pulmonary arteries in mice with PAH induced by hypoxia. In conclusion, NO-RP drugs could considerably enhance the therapeutic potential of NO therapy for PAH.
authors.affiliation: Department of Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College, Dovehouse Street, London, SW3 6LY, UK.|Heart Science Centre, Imperial College, Harefield, Uxbridge, UB9 6JH, UK.|Qatar Foundation Research and Development Division, Doha, Qatar.
authors.forename: Nura A
authors.initials: NA
authors.lastname: Mohamed
authors.affiliation: Department of Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College, Dovehouse Street, London, SW3 6LY, UK.
authors.forename: Blerina
authors.initials: B
authors.lastname: Ahmetaj-Shala
authors.affiliation: Department of Experimental Medicine and Toxicology, Hammersmith Campus, Imperial College London, Du Cane Road, London, W12 0NN, UK.
authors.forename: Lucie
authors.initials: L
authors.lastname: Duluc
authors.affiliation: School of Life and Medical Sciences, University of Hertfordshire, Hatfield, AL10 9AB, UK.
authors.forename: Louise S
authors.initials: LS
authors.lastname: Mackenzie
authors.affiliation: Department of Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College, Dovehouse Street, London, SW3 6LY, UK.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Kirkby
authors.affiliation: Department of Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College, Dovehouse Street, London, SW3 6LY, UK.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Reed
authors.affiliation: Synthesis Section, Department of Chemistry, Imperial College London, South Kensington, London, SW7 2AZ, UK.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Lickiss
authors.affiliation: Synthesis Section, Department of Chemistry, Imperial College London, South Kensington, London, SW7 2AZ, UK.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Davies
authors.affiliation: Synthesis Section, Department of Chemistry, Imperial College London, South Kensington, London, SW7 2AZ, UK.
authors.forename: Gemma R
authors.initials: GR
authors.lastname: Freeman
authors.affiliation: Department of Experimental Medicine and Toxicology, Hammersmith Campus, Imperial College London, Du Cane Road, London, W12 0NN, UK.
authors.forename: Beata
authors.initials: B
authors.lastname: Wojciak-Stothard
authors.affiliation: Heart Science Centre, Imperial College, Harefield, Uxbridge, UB9 6JH, UK.
authors.forename: Adrian H
authors.initials: AH
authors.lastname: Chester
authors.affiliation: Center for Materials Science, Zewail City, Sheikh, Zayed District, 12588, 6th of October City, Giza, Egypt.
authors.forename: Ibrahim M
authors.initials: IM
authors.lastname: El-Sherbiny
authors.affiliation: Department of Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College, Dovehouse Street, London, SW3 6LY, UK.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Mitchell
authors.affiliation: Heart Science Centre, Imperial College, Harefield, Uxbridge, UB9 6JH, UK. m.yacoub@imperial.ac.uk.
authors.forename: Magdi H
authors.initials: MH
authors.lastname: Yacoub
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D062186:Arterial Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007700:Kinetics; D051379:Mice; D050997:Nanomedicine; D053758:Nanoparticles; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000959:Antihypertensive Agents; D020030:Nitric Oxide Donors; D009569:Nitric Oxide
keywords: Aorta; Endothelial cells; NO-releasing nanoparticles; Nanomedicine; Nanoparticles; Nitric oxide; Pulmonary arterial hypertension; Pulmonary artery; Pulmonary artery vascular smooth muscle cells