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The nasal absorption of a series of peptides was studied in order to examine the relationship between extent of absorption and lipophilicity and absorption enhancers were used to probe the mechanism of peptide absorption. An in situ rat nasal perfusion technique was employed to assess the nasal absorption of a series of peptides, D-FGGGGG (D-FG5), D-FD-FGGGG (D-F2G4) and D-FD-FD-FGGG (D-F3G3), [D-ala2, D-leu5]enkephalin (YD-AGFD-L) and thyrotrophin releasing hormone (TRH). The enhancers sodium tauro-24,25 dihydrofusidate (STDHF), ethylene diamine tetraacetic acid (EDTA and dimethyl-beta-cyclodextrin (DMbetaCD) were utilized to improve and elucidate the mechanisms of peptide absorption. There was no significant relationship between extent of peptide absorption and lipophilicity as determined by C log P values. STDHF was a potent absorption enhancer but demonstrated overt toxicity. Conversely, EDTA did not demonstrate extensive toxicity but was found to be a poor absorption enhancer. DMbetaCD displayed some toxicity and was also found to inhibit the absorption of D-FG5,D-F2G4 and D-F3G3. This reduction is likely to be a result of the peptide/DMbetaCD complex formation. The peptides studied appear to be predominantly absorbed by a passive paracellular mechanism.




Donnelly, A., Kellaway, I. W., Taylor, G., & Gibson, M. (1998). Absorption enhancers as tools to determine the route of nasal absorption of peptides. Journal of Drug Targeting, 5(2), 121–127. https://doi.org/10.3109/10611869808995865

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