A phosphinic acid dipeptide analogue to stabilize peptide drugs during their intranasal absorption.
Pharm Res
; 9(5): 626-8, 1992 May.
Article
en En
| MEDLINE
| ID: mdl-1608893
A major challenge in intranasal delivery of peptides is to overcome the enzymatic barrier that limits their absorption. Aminopeptidase inhibitors may be useful for improving systemic delivery of peptide drugs administered nasally. A phosphinic acid dipeptide analogue, a transition-state analogue aminopeptidase inhibitor in which the phosphinate moiety exists in a tetrahedral state mimicking peptides during their enzymatic hydrolysis, was synthesized and tested nasally in situ in rats. This inhibitor was found to inhibit greatly the degradation of the model peptide leucine-enkephalin in the nasal perfusate at less than or equal to 2 microM concentrations. The nasal peptidase hydrolytic activity was reversible after exposure to the inhibitor. This inhibitor has the advantage of efficacy at very low concentrations and reversibility of effects.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ácidos Fosfínicos
/
Encefalina Leucina
/
Dipéptidos
Límite:
Humans
Idioma:
En
Revista:
Pharm Res
Año:
1992
Tipo del documento:
Article
Pais de publicación:
Estados Unidos