title: Prolonged vasodilatory response to nanoencapsulated sildenafil in pulmonary hypertension.
abstract: Direct vasodilator delivery to the airways enables a selective therapy of pulmonary hypertension (PH). However, short-term effects of the applied medication require multiple daily inhalations. Controlled release formulations (polymeric nanomedicines) offer the potential of prolonging drug effects within the respiratory tract, thereby reducing the number of necessary inhalations. In the model of U46619-elicited PH, sildenafil and two sildenafil-loaded polymeric submicron particle formulations were evaluated for their pharmacodynamic and pharmacokinetic characteristics and acute tolerability. Lung-delivered sildenafil caused a selective dose-dependent decline of the pulmonary arterial pressure and vascular resistance. Compared to the transient pharmacodynamic effect observed for sildenafil, the same dose of nanoencapsulated sildenafil resulted in prolongation, but not augmentation, of the pulmonary vasodilatation. An extended pharmacokinetic profile was observed for nanoencapsulated sildenafil, and nanomedicines revealed no acute toxicity. The amplification of pulmonary vasodilatory response caused by nanoencapsulation of sildenafil offers an intriguing approach to ameliorate the therapy of PH. From the Clinical Editor: Pulmonary hypertension usually results in right heart failure long term. Current medical therapy includes the use of potent vasodilators such as sildenafil. In this article, the authors investigated the use of nanoencapsulated formulation for sustained delivery via inhalation route. An extended pharmacokinetic profile was seen for this nanoformulation with little side effects. It is hoped that clinical application of this would come to fruition soon.
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Lung Center (DZL), Justus-Liebig-Universität, Giessen, Germany; Department of Pharmaceutics and Biopharmacy, Philipps-Universität, Marburg, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Beck-Broichsitter
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Lung Center (DZL), Justus-Liebig-Universität, Giessen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hecker
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Lung Center (DZL), Justus-Liebig-Universität, Giessen, Germany.
authors.forename: Djuro
authors.initials: D
authors.lastname: Kosanovic
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Lung Center (DZL), Justus-Liebig-Universität, Giessen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmehl
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Lung Center (DZL), Justus-Liebig-Universität, Giessen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Gessler
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Lung Center (DZL), Justus-Liebig-Universität, Giessen, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Weissmann
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Lung Center (DZL), Justus-Liebig-Universität, Giessen, Germany.
authors.forename: Hossein Ardeschir
authors.initials: HA
authors.lastname: Ghofrani
authors.affiliation: Department of Pharmaceutics and Biopharmacy, Philipps-Universität, Marburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kissel
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Lung Center (DZL), Justus-Liebig-Universität, Giessen, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Lung Center (DZL), Justus-Liebig-Universität, Giessen, Germany. Electronic address: ralph.schermuly@innere.med.uni-giessen.de.
authors.forename: Ralph Theo
authors.initials: RT
authors.lastname: Schermuly
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D004058:Diffusion; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology*; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D011652:Pulmonary Circulation / Q000187:drug effects*; D011817:Rabbits; D000068677:Sildenafil Citrate / Q000008:administration & dosage* / Q000737:chemistry; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D003692:Delayed-Action Preparations; D053769:Nanocapsules; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate
keywords: Controlled drug release; Polymeric nanomedicines; Prolonged vasodilation; Pulmonary drug delivery; Pulmonary hypertension; Sildenafil