GLYCOSILATED MACROMOLECULAR CONJUGATES OF ANTIVIRAL DRUGS WITH A POLYASPARTAMIDE

Gaetano Giammona, Gennara Cavallaro, Laura Maniscalco, Alessandra Semenzato, Stefano Salmaso, Paolo Caliceti

Risultato della ricerca: Article

21 Citazioni (Scopus)

Abstract

Two new polymeric conjugates for specific liver targeting were prepared by conjugation of sugar moieties and antiviral drugs to alpha, beta-poly[N-2-(hydroxyethyl)-DL-aspartamide] (PHEA). PHEA-galactopyranosylphenylthiocarbamide-mono-O-succinylganciclovir (conjugate 7) and PHEA-mannopyranosylphenylthiocarbamide-O-succinylacyclovir (conjugate 8) were synthesized according to a multi-step procedure which allowed for obtaining high product yield and process standardization. Conjugate 7 contained 7.5 and 8.5% of galactose and ganciclovir (substituent/repeating unit, mol/mol), respectively, and conjugate 8 contained 14.2 and 10.8% of mannose and acyclovir, respectively. In vitro studies demonstrated that both acyclovir and ganciclovir are released from the polymeric adducts at a release rate, which depended on the incubation medium. Though a detailed study evidenced that the two bioconjugates undergo different hydrolysis pathways, in both cases high drug release rate was found in plasma, while the glycosidic moiety was not released. Pharmacokinetic studies carried out by intravenous administration of the bioconjugates to Balb/c mice demonstrated that the conjugation of glycosidic moieties promotes the disappearance of the polymer from the bloodstream. The two derivatives displayed a different pharmacokinetic profile. In particular, the mannosyl conjugation promoted the rapid disposition of the macromolecule in the kidneys and in the liver, while prevented the accumulation in the spleen. On the contrary, the galactosyl derivative was found to dispose in the liver at the same extent of the naked polymer. Few considerations on the different behavior of the conjugates were reported.
Lingua originaleEnglish
pagine (da-a)593-605
Numero di pagine13
RivistaJournal of Drug Targeting
Volume12
Stato di pubblicazionePublished - 2004

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cita questo

GLYCOSILATED MACROMOLECULAR CONJUGATES OF ANTIVIRAL DRUGS WITH A POLYASPARTAMIDE. / Giammona, Gaetano; Cavallaro, Gennara; Maniscalco, Laura; Semenzato, Alessandra; Salmaso, Stefano; Caliceti, Paolo.

In: Journal of Drug Targeting, Vol. 12, 2004, pag. 593-605.

Risultato della ricerca: Article

@article{17634ca6dfc44db9bc4a7174b012cca2,
title = "GLYCOSILATED MACROMOLECULAR CONJUGATES OF ANTIVIRAL DRUGS WITH A POLYASPARTAMIDE",
abstract = "Two new polymeric conjugates for specific liver targeting were prepared by conjugation of sugar moieties and antiviral drugs to alpha, beta-poly[N-2-(hydroxyethyl)-DL-aspartamide] (PHEA). PHEA-galactopyranosylphenylthiocarbamide-mono-O-succinylganciclovir (conjugate 7) and PHEA-mannopyranosylphenylthiocarbamide-O-succinylacyclovir (conjugate 8) were synthesized according to a multi-step procedure which allowed for obtaining high product yield and process standardization. Conjugate 7 contained 7.5 and 8.5{\%} of galactose and ganciclovir (substituent/repeating unit, mol/mol), respectively, and conjugate 8 contained 14.2 and 10.8{\%} of mannose and acyclovir, respectively. In vitro studies demonstrated that both acyclovir and ganciclovir are released from the polymeric adducts at a release rate, which depended on the incubation medium. Though a detailed study evidenced that the two bioconjugates undergo different hydrolysis pathways, in both cases high drug release rate was found in plasma, while the glycosidic moiety was not released. Pharmacokinetic studies carried out by intravenous administration of the bioconjugates to Balb/c mice demonstrated that the conjugation of glycosidic moieties promotes the disappearance of the polymer from the bloodstream. The two derivatives displayed a different pharmacokinetic profile. In particular, the mannosyl conjugation promoted the rapid disposition of the macromolecule in the kidneys and in the liver, while prevented the accumulation in the spleen. On the contrary, the galactosyl derivative was found to dispose in the liver at the same extent of the naked polymer. Few considerations on the different behavior of the conjugates were reported.",
author = "Gaetano Giammona and Gennara Cavallaro and Laura Maniscalco and Alessandra Semenzato and Stefano Salmaso and Paolo Caliceti",
year = "2004",
language = "English",
volume = "12",
pages = "593--605",
journal = "Journal of Drug Targeting",
issn = "1061-186X",
publisher = "Informa Healthcare",

}

TY - JOUR

T1 - GLYCOSILATED MACROMOLECULAR CONJUGATES OF ANTIVIRAL DRUGS WITH A POLYASPARTAMIDE

AU - Giammona, Gaetano

AU - Cavallaro, Gennara

AU - Maniscalco, Laura

AU - Semenzato, Alessandra

AU - Salmaso, Stefano

AU - Caliceti, Paolo

PY - 2004

Y1 - 2004

N2 - Two new polymeric conjugates for specific liver targeting were prepared by conjugation of sugar moieties and antiviral drugs to alpha, beta-poly[N-2-(hydroxyethyl)-DL-aspartamide] (PHEA). PHEA-galactopyranosylphenylthiocarbamide-mono-O-succinylganciclovir (conjugate 7) and PHEA-mannopyranosylphenylthiocarbamide-O-succinylacyclovir (conjugate 8) were synthesized according to a multi-step procedure which allowed for obtaining high product yield and process standardization. Conjugate 7 contained 7.5 and 8.5% of galactose and ganciclovir (substituent/repeating unit, mol/mol), respectively, and conjugate 8 contained 14.2 and 10.8% of mannose and acyclovir, respectively. In vitro studies demonstrated that both acyclovir and ganciclovir are released from the polymeric adducts at a release rate, which depended on the incubation medium. Though a detailed study evidenced that the two bioconjugates undergo different hydrolysis pathways, in both cases high drug release rate was found in plasma, while the glycosidic moiety was not released. Pharmacokinetic studies carried out by intravenous administration of the bioconjugates to Balb/c mice demonstrated that the conjugation of glycosidic moieties promotes the disappearance of the polymer from the bloodstream. The two derivatives displayed a different pharmacokinetic profile. In particular, the mannosyl conjugation promoted the rapid disposition of the macromolecule in the kidneys and in the liver, while prevented the accumulation in the spleen. On the contrary, the galactosyl derivative was found to dispose in the liver at the same extent of the naked polymer. Few considerations on the different behavior of the conjugates were reported.

AB - Two new polymeric conjugates for specific liver targeting were prepared by conjugation of sugar moieties and antiviral drugs to alpha, beta-poly[N-2-(hydroxyethyl)-DL-aspartamide] (PHEA). PHEA-galactopyranosylphenylthiocarbamide-mono-O-succinylganciclovir (conjugate 7) and PHEA-mannopyranosylphenylthiocarbamide-O-succinylacyclovir (conjugate 8) were synthesized according to a multi-step procedure which allowed for obtaining high product yield and process standardization. Conjugate 7 contained 7.5 and 8.5% of galactose and ganciclovir (substituent/repeating unit, mol/mol), respectively, and conjugate 8 contained 14.2 and 10.8% of mannose and acyclovir, respectively. In vitro studies demonstrated that both acyclovir and ganciclovir are released from the polymeric adducts at a release rate, which depended on the incubation medium. Though a detailed study evidenced that the two bioconjugates undergo different hydrolysis pathways, in both cases high drug release rate was found in plasma, while the glycosidic moiety was not released. Pharmacokinetic studies carried out by intravenous administration of the bioconjugates to Balb/c mice demonstrated that the conjugation of glycosidic moieties promotes the disappearance of the polymer from the bloodstream. The two derivatives displayed a different pharmacokinetic profile. In particular, the mannosyl conjugation promoted the rapid disposition of the macromolecule in the kidneys and in the liver, while prevented the accumulation in the spleen. On the contrary, the galactosyl derivative was found to dispose in the liver at the same extent of the naked polymer. Few considerations on the different behavior of the conjugates were reported.

UR - http://hdl.handle.net/10447/10055

M3 - Article

VL - 12

SP - 593

EP - 605

JO - Journal of Drug Targeting

JF - Journal of Drug Targeting

SN - 1061-186X

ER -