ABSORPTION ENHANCERS AS TOOLS TO DETERMINE THE ROUTE OF NASAL ABSORPTION OF PEPTIDES

The nasal absorption of a series of peptides was studied in order to e xamine 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 a ssess the nasal absorption of a series of peptides, D-FGGGGG (D-FG(5)) , D-FD-FGGGG (D-F(2)G(4)) and o-FD-FD-FGGG (D-F(3)G(3)), [D-ala(2), D- leu(5)]enkephalin (YD-AGFD-L) and thyrotrophin releasing hormone (TRH) . The enhancers sodium tauro-24,25 dihydrofusidate (STDHF), ethylene d iamine tetraacetic acid (EDTA and dimethyl-beta-cyclodextrin (DM beta CD) were utilized to improve and elucidate the mechanisms of peptide a bsorption. There was no significant relationship between extent of pep tide absorption and lipophilicity as determined by C log P values. STD HF was a potent absorption enhancer but demonstrated overt toxicity. C onversely, EDTA did not demonstrate extensive toxicity but was found t o be a poor absorption enhancer. DM beta CD displayed some toxicity an d was also found to inhibit the absorption of D-FG(5),D-F(2)G(4) and D -F(3)G(3). This reduction is likely to be a result of the peptide/DM b eta CD complex formation. The peptides studied appear to be predominan tly absorbed by a passive paracellular mechanism.