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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/26351

Title: A Biocompatible Synthetic Lung Fluid Based on Human Respiratory Tract Lining Fluid Composition
Authors: Kumar, Abhinav
Terakosolphan, Wachirun
Hassoun, Mireille
Vandera, Kalliopi-Kelli
Novicky, Astrid
Harvey, Richard
Royall, Paul G.
Bicer, Elif Melis
Eriksson, Jonny
Edwards, Katarina
Valkenborg, Dirk
Nelissen, Inge
Hassall, Dave
Mudway, Ian S.
Forbes, Ben
Issue Date: 2017
Citation: PHARMACEUTICAL RESEARCH, 34(12), p. 2454-2465
Abstract: To characterise a biorelevant simulated lung fluid (SLF) based on the composition of human respiratory tract lining fluid. SLF was compared to other media which have been utilized as lung fluid simulants in terms of fluid structure, biocompatibility and performance in inhalation biopharmaceutical assays. The structure of SLF was investigated using cryo-transmission electron microscopy, photon correlation spectroscopy and Langmuir isotherms. Biocompatibility with A549 alveolar epithelial cells was determined by MTT assay, morphometric observations and transcriptomic analysis. Biopharmaceutical applicability was evaluated by measuring the solubility and dissolution of beclomethasone dipropionate (BDP) and fluticasone propionate (FP), in SLF. SLF exhibited a colloidal structure, possessing vesicles similar in nature to those found in lung fluid extracts. No adverse effect on A549 cells was apparent after exposure to the SLF for 24 h, although some metabolic changes were identified consistent with the change of culture medium to a more lung-like composition. The solubility and dissolution of BDP and FP in SLF were enhanced compared to Gamble's solution. The SLF reported herein constitutes a biorelevant synthetic simulant which is suitable to study biopharmaceutical properties of inhalation medicines such as those being proposed for an inhaled biopharmaceutics classification system.
Notes: [Kumar, Abhinav; Terakosolphan, Wachirun; Hassoun, Mireille; Vandera, Kalliopi-Kelli; Novicky, Astrid; Harvey, Richard; Royall, Paul G.; Forbes, Ben] Kings Coll London, Inst Pharmaceut Sci, Fac Life Sci & Med, London SE1 9NH, England. [Harvey, Richard] Martin Luther Univ Halle Wittenberg, Inst Pharm, D-06108 Halle, Saale, Germany. [Bicer, Elif Melis; Mudway, Ian S.] Kings Coll London, MRC PHE Ctr Environm & Hlth, London SE1 9NH, England. [Bicer, Elif Melis; Mudway, Ian S.] Kings Coll London, Fac Life Sci & Med, Environm & Analyt Res Div, NIHR HPRU Hlth Impact Environm Hazards, London SE1 9NH, England. [Eriksson, Jonny; Edwards, Katarina] Uppsala Univ, Dept Chem BMC, Uppsala, Sweden. [Valkenborg, Dirk; Nelissen, Inge] VITO NV, Hlth Unit, B-2400 Mol, Belgium. [Valkenborg, Dirk] Hasselt Univ, Interuniv Inst Biostat & Stat Bioinformat, B-3500 Hasselt, Belgium. [Valkenborg, Dirk] Univ Antwerp, Ctr Prote, B-2000 Antwerp, Belgium. [Hassall, Dave] GSK Med Res Ctr, Gunnels Wood Rd, Stevenage SG1 2NY, Herts, England.
URI: http://hdl.handle.net/1942/26351
DOI: 10.1007/s11095-017-2169-4
ISI #: 000418390000002
ISSN: 0724-8741
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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