Systematic investigations of the influence of molecular structure on the transport of peptides across cultured alveolar cell monolayers.
OBJECTIVE
To determine how the structures of peptides influence their alveolar permeability.


METHODS
The studies were performed using 14 synthetic 'model' peptides, labelled with a novel, non-intrusive amino acid fluorophore, and their transport studied using rat alveolar cell monolayers cultured on permeable supports.


RESULTS
The passage of the peptides across the epithelial cell monolayers is shown to be primarily paracellular, with an inverse dependence on molecular size, and an enhanced flux observed for cationic peptides. The apparent permeability coefficients (Papp) for the peptides (together with those for other organic solutes, taken from the literature) are shown to be well-modelled assuming two populations of 'pores' in the monolayers, modelled as cylindrical channels of radii 15 A and 22 nm. The former pores are shown to be numerically equitable with the monolayer tri-junctional complexes, and the latter are taken as monolayer defects.


CONCLUSIONS
The various monolayer Papp values correlate well with the results from in vivo transport experiments, and the conclusion is drawn that the pulmonary delivery of peptide drugs is perfectly exploitable.
Dodoo
A N
AN
Department of Pharmacy, King's College London, England.
Bansal
S
S
Barlow
D J
DJ
Bennet
F C
FC
Hider
R C
RC
Lansley
A B
AB
Lawrence
M J
MJ
Marriott
C
C
D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D008297:Male; D010455:Peptides / Q000493:pharmacokinetics*; D010539:Permeability; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D010455:Peptides