Alaa S Tulbah1,2, Hui Xin Ong1, Wing-Hin Lee1, Paolo Colombo3, Paul M Young1, Daniela Traini4. 1. Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, Sydney University, Sydney, NSW, 2037, Australia. 2. Faculty of Pharmacy, Umm Al Qura University, Makkah, Saudi Arabia. 3. Department of Pharmacy, University of Parma, Parma, Italy. 4. 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.
Abstract
PURPOSE: 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.
PURPOSE: 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: Cheng Yuan; Lin Zhou; Jiyun Cheng; Jingying Zhang; Yue Teng; Mao Huang; Ian M Adcock; Peter J Barnes; Xin Yao Journal: Respir Res Date: 2012-11-24