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Titolo:
Chemical stability, enzymatic hydrolysis, and nasal uptake of amino acid ester prodrugs of acyclovir
Autore:
Yang, C; Gao, H; Mitra, AK;
Indirizzi:
Univ Missouri, Sch Pharm, Div Pharmaceut Sci, Kansas City, MO 64110 USA Univ Missouri Kansas City MO USA 64110 eut Sci, Kansas City, MO 64110 USA
Titolo Testata:
JOURNAL OF PHARMACEUTICAL SCIENCES
fascicolo: 5, volume: 90, anno: 2001,
pagine: 617 - 624
SICI:
0022-3549(200105)90:5<617:CSEHAN>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
DRUG-DELIVERY; PEPTIDE TRANSPORTER; ABSORPTION; MUCOSA; RAT;
Keywords:
nasal drug delivery; acyclovir; prodrug; active transport; amino acid transporter; peptide transporter;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
22
Recensione:
Indirizzi per estratti:
Indirizzo: Mitra, AK Univ Missouri, Sch Pharm, Div Pharmaceut Sci, 5005 Rockhill Rd, Kansas City, MO 64110 USA Univ Missouri 5005 Rockhill Rd Kansas City MO USA64110 4110 USA
Citazione:
C. Yang et al., "Chemical stability, enzymatic hydrolysis, and nasal uptake of amino acid ester prodrugs of acyclovir", J PHARM SCI, 90(5), 2001, pp. 617-624

Abstract

The objective of this work was to improve nasal absorption of relatively impermeable small drug molecules via an amino acid prodrug approach. Acyclovir was selected as a model drug. L-Aspartate beta -ester, L-lysyl, and L-phenylalanyl eaters of acyclovir were synthesized to investigate their effectiveness in enhancing nasal absorption of acyclovir. A stability study was conducted in phosphate buffer under various pH conditions at 25 and 37 degreesC. Enzymatic hydrolysis in rat nasal washings and plasma was conducted at37 degreesC. A rat in situ nasal perfusion technique was utilized in this investigation to examine the rate and extent of nasal absorption of amino acid prodrugs. The remaining analyte concentrations in the nasal perfusate were quantitated by reversed-phase high-performance liquid chromatography. The results revealed that the L-lysyl and L-phenylalanyl esters were less stable than L-aspartate beta -ester. The stability of all three esters decreased with increasing FH and temperature. L-phenylalanyl ester is highly susceptible to plasma esterases, with an in vitro half-life 1.33 min. The rat in situ nasal perfusion study revealed that the extent of nasal absorption of acyclovir, L-lysyl and L-phenylalanyl eaters was not significant (p < 1%). L-Aspartate beta -ester was absorbed to the extent of similar to8% over 90 min of perfusion at an initial drug concentration of 100 muM. Nasal absorption of L-aspartate beta -ester of acyclovir was inhibited by L-asparaginebut not by a dipeptide glycylsarcosine (Gly-Sar). The enhancement of acyclovir nasal absorption from the L-aspartate p-ester prodrug suggests that nasal uptake of this prodrug probably involves an active transport system. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J PharmSci 90:617-624, 2001.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/03/20 alle ore 23:00:00