title: Biological Effects of Simvastatin Formulated as pMDI on Pulmonary Epithelial Cells.
abstract: OBJECTIVE
  The aim of this study is to evaluate the biological effects of Calu-3 epithelial cells in response to the delivery of simvastatin (SV) via solution pressurized metered dose inhaler (pMDI).
  
  
  METHODS
  SV pMDI was aerosolised onto Calu-3 air-interface epithelial cells using a modified glass twin stage impinger. The transport of SV across Calu-3 cells, mucus production, inflammatory cytokines production i.e., interleukin (IL) 6, 8 and tumour necrosis factor alpha (TNF- α) and oxidative stress from Calu-3 cells following treatment with SV pMDI was investigated and compared to untreated cells.
  
  
  RESULTS
  It was found that SV had the ability to penetrate into the respiratory epithelium and convert into its active SV hydroxy acid (SVA) metabolite. Furthermore, the amount of mucus produced was significantly reduced when SV was deposited on Calu-3 compared to untreated cells. Additionally, SV delivered by pMDI reduces production of IL-6, 8 and TNF-α from Calu-3 following stimulation with lipopolysaccharide (LPS). SV also showed equivalent antioxidant property to vitamin E.
  
  
  CONCLUSIONS
  Treatment with SV solution pMDI formulation on Calu-3 cells reduces mucus production, inflammatory cytokines and oxidative stress. This formulation could potentially be used clinically as muco-inhibitory and anti-inflammatory therapy for treatment of chronic lung diseases.
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, Sydney University, Sydney, NSW, 2037, Australia.|Faculty of Pharmacy, Umm Al Qura University, Makkah, Saudi Arabia.
authors.forename: Alaa S
authors.initials: AS
authors.lastname: Tulbah
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, Sydney University, Sydney, NSW, 2037, Australia.
authors.forename: Hui Xin
authors.initials: HX
authors.lastname: Ong
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, Sydney University, Sydney, NSW, 2037, Australia.
authors.forename: Wing-Hin
authors.initials: WH
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, University of Parma, Parma, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Colombo
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, Sydney University, Sydney, NSW, 2037, Australia.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Young
authors.affiliation: Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, Sydney University, Sydney, NSW, 2037, Australia. daniela.traini@sydney.edu.au.
authors.forename: Daniela
authors.initials: D
authors.lastname: Traini
mesh_terms: D000336:Aerosols; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D016207:Cytokines / Q000096:biosynthesis; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D008168:Lung / Q000166:cytology* / Q000187:drug effects*; D036501:Metered Dose Inhalers; D009093:Mucus / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects*; D019821:Simvastatin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000336:Aerosols; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017382:Reactive Oxygen Species; D019821:Simvastatin
keywords: Calu-3 epithelial cell; anti-inflammatory; mucus; pMDI; simvastatin