title: Biopharmaceutical Evaluation of Novel Cyclosporine A Nano-matrix Particles for Inhalation.
abstract: This study was undertaken to evaluate the biopharmaceutical properties of cyclosporine A (CsA)-loaded nano-matrix particles for inhalation.
  
  
  
  Nano-matrix particles of CsA with mannitol (nCsAm) were prepared by a flash nano-precipitation technique employing a multi-inlet vortex mixer and evaluated in terms of physicochemical properties, anti-inflammatory effect in the rat model of airway inflammation, pharmacokinetic behavior, and distributions of CsA to side-effect-related organs after intratracheal administration.
  
  
  
  In nCsAm, spherical nano-particles of CsA were covered with mannitol and the mean particle size was 1.3 μm. The in vitro Next Generation Impactor analysis demonstrated fine inhalation performance with a fine particle fraction value of 65.8%. Intratracheal nCsAm (100 μg-CsA/rat) significantly attenuated the recruitment of inflammatory cells into the airway in the rat model of airway inflammation, followed by suppression of the inflammatory biomarkers. After intratracheal nCsAm at a pharmacologically effective dose (100 μg-CsA/rat), there was a 42-47-fold decrease in the distribution of CsA to side-effect-related organs such as the kidney and liver compared with oral CsA at a toxic dose (10 mg-CsA/kg), potentially leading to avoidance of systemic side-effects of CsA.
  
  
  
  Upon these findings, nCsAm prepared with the flash nano-precipitation technique could be a novel dosage form of CsA for inhalation therapy of airway inflammation with a better safety margin.
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yakushiji
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Building A15, Sydney, NSW, 2006, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wong
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Seto
authors.affiliation: Department of Chemical & Biological Engineering, Princeton University, A301 EQUAD, Princeton, New Jersey, 08544, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Prud'homme
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Building A15, Sydney, NSW, 2006, Australia. kim.chan@sydney.edu.au.
authors.forename: Hak-Kim
authors.initials: HK
authors.lastname: Chan
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan. onoue@u-shizuoka-ken.ac.jp.
authors.forename: Satomi
authors.initials: S
authors.lastname: Onoue
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016572:Cyclosporine / Q000008:administration & dosage* / Q000737:chemistry*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008353:Mannitol / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D008353:Mannitol; D016572:Cyclosporine
keywords: anti-inflammatory effect; cyclosporine A; inhalation; nano-matrix particles; pharmacokinetic control