A methodology was developed to determine the type and activity of aminopeptidases in the conjunetival, nasal, buccal, rectal and vaginal homogenates, relative to duodenal and ileal homogenates, so as to define the aminopeptidase barrier to peptide absorption from non-oral routes. 4-Methoxy-2-naphthylamides of leucine, alanine, arginine and glutamic acid were used as substrates. Based on the pattern of substrate hydrolysis and the effect of activators and inhibitors on the rate of substrate hydrolysis, four to five aminopeptidases were estimated to be present in the mucosal homogenates studied. Aminopeptidase N was present in all these mucosae to the extent of 50-100% of ileal activity, whereas aminopeptidase A was present to the extent of 4-20% of ileal activity. Overall, the differences in aminopeptidase activity among the various non-oral routes were not large. This suggests that, before guidelines can be established to select a given route for optimal peptide delivery, further work is necessary to determine if the non-oral routes differ in non-aminopeptidase activity and in membrane permeability.
- aminopeptidases-peptide bioavailability-nasal route-buccal route-vaginal route-rectal route-oral peptide delivery
ASJC Scopus subject areas
- Pharmaceutical Science