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Titolo:
Oral absorption of peptides through the cobalamin (vitamin B12) pathway inthe rat intestine
Autore:
Alsenz, J; Russell-Jones, GJ; Westwood, S; Levet-Trafit, B; de Smidt, PC;
Indirizzi:
F Hoffmann La Roche & Co Ltd, Div Pharma, Preclin Res Dept, CH-4070 Basel,Switzerland F Hoffmann La Roche & Co Ltd Basel Switzerland CH-4070 Basel,Switzerland Biotech Australia Pty, Dept Res & Dev, Roseville, NSW 2069, Australia Biotech Australia Pty Roseville NSW Australia 2069 e, NSW 2069, Australia Univ Navarra, Fac Pharm, Dept Pharm & Pharmaceut Technol, E-31080 Pamplona, Spain Univ Navarra Pamplona Spain E-31080 eut Technol, E-31080 Pamplona, Spain
Titolo Testata:
PHARMACEUTICAL RESEARCH
fascicolo: 7, volume: 17, anno: 2000,
pagine: 825 - 832
SICI:
0724-8741(200007)17:7<825:OAOPTT>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSCOBALAMIN-II RECEPTOR; CACO-2 CELLS; PENETRATION ENHANCEMENT; MEDIATED ENDOCYTOSIS; DRUG DELIVERY; BILE-ACIDS; IN-VITRO; TRANSPORT; PROTEINS; ROUTES;
Keywords:
cobalamin(vitamin B12); in vitro-in vivo study; cblpeptide conjugate; oral absorption;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Alsenz, J F Hoffmann La Roche & Co Ltd, Div Pharma, Preclin Res Dept, CH-4070 Basel,Switzerland F Hoffmann La Roche & Co Ltd Basel Switzerland CH-4070 zerland
Citazione:
J. Alsenz et al., "Oral absorption of peptides through the cobalamin (vitamin B12) pathway inthe rat intestine", PHARM RES, 17(7), 2000, pp. 825-832

Abstract

Purpose. This study was aimed at examining the extent and mechanism of uptake of cobalamin (Cbl)-conjugated peptides in vitro and in vivo. Methods. To enable acquisition of quantitative absorption data of Cbl-peptides, metabolically stable octapeptides (DP3), with (Cbl-Hex-DP3) or without a hexyl spacer (Cbl-DP3), were coupled to Cbl and radiolabeled. For comparison, LHRH coupled to Cbl was used as metabolically susceptible peptide. Biological recognition of Cbl-peptides was studied in the physiological order: binding by Intrinsic Factor (IF), recognition and transport of the IF-complexes by IF-Cbl receptors (IFCR) on Caco-2 monolayers and oral absorptionof the Cbl-conjugates in the rat. Results. All Cbl-peptides bound to IF and the IF-complexes were recognizedby IFCR receptors on Caco-2 monolayers. Binding was saturable and could beinhibited by a 20-fold excess of IF-Cbl, but not of Non-intrinsic Factor (NIF)-Cbl. Oral administration of these ligands to rats resulted in absorption of 53%, 45%, 42%, and 23% of the applied radioactivity for Cbl, Cbl-LHRH, Cbl-Hex-DP3, and Cbl-DP3, respectively. Simultaneous administration of a >10(5)-fold excess of unlabeled Cbl reduced uptake of all compounds to <4%. Tissue distribution and elimination of the metabolically stable Cbl-conjugates were comparable to Cbl. Conclusions. The endogenous Cbl uptake pathway can be exploited for oral peptide delivery as indicated by the specific and high (40-45%) uptake of metabolically stable Cbl-coupled octapeptides.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 17:29:29