title: Inhaled sildenafil nanocomposites: lung accumulation and pulmonary pharmacokinetics.
abstract: BACKGROUND
  Administration of sildenafil citrate (SC) is considered as a strategy in the treatment of pulmonary hypertension.
  
  
  OBJECTIVE
  This study reports production of the inhalable microparticles containing SC-loaded poly(lactide-co-glycolic acid)-nanoparticles.
  
  
  METHODS
  SC-nanoparticles were prepared by the double emulsion solvent evaporation method. Next, free SC and SC-loaded nanoparticles were spray dried in the presence of appropriate excipients (lactose, maltose and trehalose). Physicochemical properties and aerodynamic behavior of prepared powders were evaluated. In addition, drug accumulation from selected formulations in the rat lung tissue was compared with oral and IV administration.
  
  
  RESULTS
  Size and fine particle fraction of selected nanocomposites and free SC microparticles were 7 and 4.5 µm, and 60.2% and 68.2%, respectively. Following oral and IV administration, the drug was not detectable in the lung after 4 and 6 h, respectively, but in SC-loaded nanoparticles, the drug was detectable in the lung even after 12 h of inhalation. Respirable particles containing free SC provided high concentration at first that was detectable up to 6 after insufflation.
  
  
  CONCLUSIONS
  In vivo study demonstrated that pulmonary administration of sildenafil and sildenafil nanoparticles produced longer half-life and higher concentration of the drug in the lung tissue as compared to oral and IV administration. So, these formulations could be more effective than oral and IV administration of this drug.
authors.affiliation: a Pharmaceutics Department , Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran , Iran and.
authors.forename: Elham
authors.initials: E
authors.lastname: Ghasemian
authors.affiliation: a Pharmaceutics Department , Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran , Iran and.
authors.forename: Alireza
authors.initials: A
authors.lastname: Vatanara
authors.affiliation: a Pharmaceutics Department , Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran , Iran and.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Rouini
authors.affiliation: a Pharmaceutics Department , Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran , Iran and.
authors.forename: Abdolhossein
authors.initials: A
authors.lastname: Rouholamini Najafabadi
authors.affiliation: a Pharmaceutics Department , Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran , Iran and.
authors.forename: Kambiz
authors.initials: K
authors.lastname: Gilani
authors.affiliation: a Pharmaceutics Department , Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran , Iran and.
authors.forename: Hoda
authors.initials: H
authors.lastname: Lavasani
authors.affiliation: b Department of Virology , Pasteur Institute of Iran , Tehran , Iran.
authors.forename: Nasir
authors.initials: N
authors.lastname: Mohajel
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D005079:Excipients / Q000737:chemistry; D008168:Lung / Q000378:metabolism*; D008297:Male; D053761:Nanocomposites / Q000008:administration & dosage* / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011098:Polyglactin 910 / Q000737:chemistry; D011208:Powders / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D005079:Excipients; D011208:Powders; D011098:Polyglactin 910; D000068677:Sildenafil Citrate
keywords: Controlled release; in vivo; nanoparticles; pulmonary delivery; sildenafil citrate