2. Academic Validation
  3. A Biocompatible Synthetic Lung Fluid Based on Human Respiratory Tract Lining Fluid Composition

A Biocompatible Synthetic Lung Fluid Based on Human Respiratory Tract Lining Fluid Composition

  • Pharm Res. 2017 Dec;34(12):2454-2465. doi: 10.1007/s11095-017-2169-4.
Abhinav Kumar 1,  Wachirun Terakosolphan 1,  Mireille Hassoun 1,  Kalliopi-Kelli Vandera 1,  Astrid Novicky 1,  Richard Harvey 1 2,  Paul G Royall 1,  Elif Melis Bicer 3,  Jonny Eriksson 4,  Katarina Edwards 4,  Dirk Valkenborg 5 6 7,  Inge Nelissen 5,  Dave Hassall 8,  Ian S Mudway 3,  Ben Forbes 9
Affiliations

Affiliations

  • 1 Institute of Pharmaceutical Science, Faculty of Life Sciences and Medicine, King's College London, London, SE1 9NH, UK.
  • 2 Institute of Pharmacy,, Martin-Luther-Universität Halle-Wittenberg, 06108, Halle (Saale), Germany.
  • 3 MRC-PHE Centre for Environment and Health and NIHR-HPRU in Health Impact of Environmental Hazards, Environmental and Analytical Research Division, Faculty of Life Sciences and Medicine, King's College London, London, SE1 9NH, UK.
  • 4 Department of Chemistry - BMC,, Uppsala University, Uppsala, Sweden.
  • 5 Health Unit, VITO NV, 2400, Mol, Belgium.
  • 6 Interuniversity Institute for Biostatistics and statistical Bioinformatics, Hasselt University, 3500, Hasselt, Belgium.
  • 7 Centre for Proteomics,, University of Antwerp, 2000, Antwerp, Belgium.
  • 8 GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.
  • 9 Institute of Pharmaceutical Science, Faculty of Life Sciences and Medicine, King's College London, London, SE1 9NH, UK. [email protected].
PMID: 28560698 DOI: 10.1007/s11095-017-2169-4
Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords

aerosol; beclomethasone dipropionate; biopharmaceutics; dissolution; fluticasone propionate; inhalation; solubility.

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