Aminopeptidase activity in homogenates of various absorptive mucosae m the albino rabbit: implications in peptide delivery

Robert Stratford Jr., Vincent H.L. Lee

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)73-82
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume30
Issue number1
DOIs
StatePublished - Jan 1 1986
Externally publishedYes

Fingerprint

Aminopeptidases
Mucous Membrane
Rabbits
Peptides
Hydrolysis
Glutamyl Aminopeptidase
CD13 Antigens
Cheek
Nose
Alanine
Arginine
Glutamic Acid
Permeability
Guidelines
Membranes

Keywords

  • aminopeptidases-peptide bioavailability-nasal route-buccal route-vaginal route-rectal route-oral peptide delivery

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

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abstract = "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.",
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