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Deposition and transport of linezolid mediated by a synthetic surfactant Synsurf (R) within a pressurized metered dose inhaler: a Calu-3 model

Year: 2018

Journal: Drug Des. Dev. Ther., Volume 12, page 1107–1118

Authors: van Rensburg, Lyne; van Zyl, Johann M.; Smith, Johan

Keywords: Calu-3; pMDI; linezolid; delivery vehicle; pulmonary surfactant; aerosolized particles

Background: Previous studies in our laboratory demonstrated that a synthetic peptide containing lung surfactant enhances the permeability of chemical compounds through bronchial epithelium. The purpose of this study was to test two formulations of Synsurf (R) combined with linezolid as respirable compounds using a pressurized metered dose inhaler (pMDI). Methods: Aerosolization efficiency of the surfactant-drug microparticles onto Calu-3 monolayers as an air interface culture was analyzed using a Next Generation Impactor (TM). Results: The delivered particles and drug dose showed a high dependency from the preparation that was aerosolized. Scanning electron microscopy imaging allowed for visualization of the deposited particles, establishing them as liposomal-type structures (diameter 500 nm to 2 mu m) with filamentous features. Conclusion: The different surfactant drug combinations allow for an evaluation of the significance of the experimental model system, as well as assessment of the formulations providing a possible noninvasive, site-specific, delivery model via pMDI.