Systematic investigations of the influence of molecular structure on the transport of peptides across cultured alveolar cell monolayers

Alexander N.O. Dodoo, Sukhrinder S. Bansal, David J. Barlow, Fiona Bennett, Robert C. Hider, Alison Lansley, Jayne M. Lawrence, Christopher Marriott

Research output: Contribution to journalArticle

Abstract

Purpose. To determine how the structures of peptides influence theiralveolar permeability. Methods. The studies were performed using 14 synthetic ‘model’peptides, labelled with a novel, non-intrusive amino acid fluorophore, andtheir transport studied using rat alveolar cell monolayers cultured onpermeable supports. Results. The passage of the peptides across the epithelial cellmonolayers is shown to be primarily paracellular, with an inverse dependenceon molecular size, and an enhanced flux observed for cationic peptides.The apparent permeability coefficients (P app ) for the peptides(together with those for other organic solutes, taken from the literature) areshown to be well-modelled assuming two populations of ‘pores’ in themonolayers, modelled as cylindrical channels of radii 15 Å and 22nm. The former pores are shown to be numerically equatable withthe monolayer tri-junctional complexes, and the latter are taken asmonolayer defects. Conclusions. The various monolayer P app values correlatewell with the results from in vivo transport experiments, and the conclusion isdrawn that the pulmonary delivery of peptide drugs is perfectlyexploitable.
Original languageEnglish
Pages (from-to)7-14
Number of pages8
JournalPharmaceutical research
Volume17
Issue number1
DOIs
Publication statusPublished - 31 Jan 2000

Keywords

  • transport of peptides
  • molecular structure
  • molecular size
  • cultured alveolar cell monolayers
  • alveolar permeability

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