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A Simple and Rapid Method for Deposition and Measurement of Drug Transport Across Air Interface Respiratory Epithelia

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Abstract

The purpose of this study was to present a novel and simple drug deposition method to evaluate drug transport of aerosol microparticles across airway epithelial cells. Microparticles containing ciprofloxacin HCl (Cip) and doxycycline (Dox), alone or in a 50:50% w/w ratio, were spray dried and suspended using 2H, 3H-perfluoropentane, model propellant. The suspension was then used to assess deposition, and transport of these drug microparticles across sub-bronchial epithelial Calu-3 cells was also studied. In comparison with other methods of depositing microparticles, this proposed method, using drug suspended in HPFP, provides control over the amount of drugs applied on the surface of the cells. Therefore, cell permeability studies could be conducted with considerably smaller and more reproducible doses, without the physicochemical characteristics of the drugs being compromised or the use of modified pharmacopeia impactors. The suspension of microparticles in HPFP as presented in this study has provided a non-toxic, simple, and reproducible novel method to deliver and study the permeability of specific quantity of drugs across respiratory epithelial cells in vitro.

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References

  1. Haghi M, Traini D, Young P. In vitro cell integrated impactor deposition methodology for the study of aerodynamically relevant size fractions from commercial pressurised metered dose inhalers. Pharm Res. 2014;31(7):1779–87. https://doi.org/10.1007/s11095-013-1282-2.

    Article  CAS  PubMed  Google Scholar 

  2. Fiegel J, Ehrhardt C, Schaefer UF, Lehr CM, Hanes J. Large porous particle impingement on lung epithelial cell monolayers—toward improved particle characterization in the lung. Pharmaceut Res. 2003;20(5):788–96. https://doi.org/10.1023/A:1023441804464.

    Article  CAS  Google Scholar 

  3. Bur M, Rothen-Rutishauser B, Huwer H, Lehr CM. A novel cell compatible impingement system to study in vitro drug absorption from dry powder aerosol formulations. Eur J Pharm Biopharm. 2009;72(2):350–7. https://doi.org/10.1016/j.ejpb.2008.07.019.

    Article  CAS  PubMed  Google Scholar 

  4. Hein S, Bur M, Schaefer UF, Lehr CM. A new pharmaceutical aerosol deposition device on cell cultures (PADDOCC) to evaluate pulmonary drug absorption for metered dose dry powder formulations. Eur J Pharm Biopharm. 2011;77(1):132–8. https://doi.org/10.1016/j.ejpb.2010.10.003.

    Article  CAS  PubMed  Google Scholar 

  5. Cooney D, Kazantseva M, Hickey AJ. Development of a size-dependent aerosol deposition model utilising human airway epithelial cells for evaluating aerosol drug delivery. Atla-Altern Lab Anim. 2004;32(6):581–90.

    CAS  Google Scholar 

  6. McDonnell C, Shur J, Burns J, Hipkiss D, Price R. Investigation deposition and drug absorption of budesonide microparticles using a cell compatible next generation impactor. In: Publishing DHIl, editor. Respir Drug Deliv USA 2012. p. 785–788.

  7. Haghi M, Young PM, Traini D, Jaiswal R, Gong J, Bebawy M. Time- and passage-dependent characteristics of a Calu-3 respiratory epithelial cell model. Drug Dev Ind Pharm. 2010;36(10):1207–14. https://doi.org/10.3109/03639041003695113.

    Article  CAS  PubMed  Google Scholar 

  8. Grainger CI, Greenwell LL, Lockley DJ, Martin GP, Forbes B. Culture of Calu-3 cells at the air interface provides a representative model of the airway epithelial barrier. Pharm Res. 2006;23(7):1482–90. https://doi.org/10.1007/s11095-006-0255-0.

    Article  CAS  PubMed  Google Scholar 

  9. Mathias NR, Timoszyk J, Stetsko PI, Megill JR, Smith RL, Wall DA. Permeability characteristics of Calu-3 human bronchial epithelial cells: in vitro-in vivo correlation to predict lung absorption in rats. J Drug Target. 2002;10(1):31–40. https://doi.org/10.1080/10611860290007504.

    Article  CAS  Google Scholar 

  10. Exiarch H, Haltner-Ukomadu E, Beisswenger C, Bock U. Drug delivery to the lung: permeability and physicochemical characteristics of drugs as the basis for a pulmonary biopharmaceutical classification system (pBCS). J Epithelial Biol Pharmacol. 2010;3:1–14.

    Google Scholar 

  11. Pezzulo AA, Starner TD, Scheetz TE, Traver GL, Tilley AE, Harvey BG, et al. The air-liquid interface and use of primary cell cultures are important to recapitulate the transcriptional profile of in vivo airway epithelia. Am J Physiol Lung Cell Mol Physiol. 2011;300(1):L25–31. https://doi.org/10.1152/ajplung.00256.2010.

    Article  CAS  PubMed  Google Scholar 

  12. Grainger CI, Greenwell LL, Martin GP, Forbes B. The permeability of large molecular weight solutes following particle delivery to air-interfaced cells that model the respiratory mucosa. Eur J Pharm Biopharm. 2009;71(2):318–24. https://doi.org/10.1016/j.ejpb.2008.09.006.

    Article  CAS  PubMed  Google Scholar 

  13. Rogueda PGA. HPFP, a model propellant for pMDIs. Drug Dev Ind Pharm. 2003;29(1):39–49. https://doi.org/10.1081/Ddc-120016682.

    Article  CAS  PubMed  Google Scholar 

  14. Adi H, Young PM, Chan HK, Salama R, Traini D. Controlled release antibiotics for dry powder lung delivery. Drug Dev Ind Pharm. 2010;36(1):119–26. https://doi.org/10.3109/03639040903099769.

    Article  CAS  PubMed  Google Scholar 

  15. Adi H, Young P, Chan HK, Stewart P, Agus H, Traini D. Cospray dried antibiotics for dry powder lung delivery. J Pharm Sci. 2007;97(8):3356–66.

    Article  CAS  Google Scholar 

  16. Tolnai SA. Method for viable cell count. Methods Cell Sci. 1975;1:37–8.

    Google Scholar 

  17. Haghi M, Bebawy M, Colombo P, Forbes B, Lewis DA, Salama R, et al. Towards the bioequivalence of pressurised metered dose inhalers 2. Aerodynamically equivalent particles (with and without glycerol) exhibit different biopharmaceutical profiles in vitro. Eur J Pharm Biopharm. 2014;86(1):38–45. https://doi.org/10.1016/j.ejpb.2013.02.020.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Daniela Traini.

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Haghi, M., Young, P.M. & Traini, D. A Simple and Rapid Method for Deposition and Measurement of Drug Transport Across Air Interface Respiratory Epithelia. AAPS PharmSciTech 19, 3272–3276 (2018). https://doi.org/10.1208/s12249-018-1170-5

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