PMID: 11312674Apr 21, 2001Paper

Polymeric prodrug for release of an antitumoral agent by specific enzymes

Bioconjugate Chemistry
G CavallaroGaetano Giammona

Abstract

The clinical usefulness of antitumor chemotherapy has been strongly limited by the lack of specificity of most anticancer drugs, which act also against healthy cells. The aim of this work was to design, synthesize, and evaluate a macromolecular prodrug of Cytarabine, a known antitumor drug, which is a specific substrate for plasmin enzyme whose concentration is high in various kinds of tumor mass as a result of plasminogen activator secretion. alpha,beta-Poly(N-hydroxyethyl)-DL-aspartamide (PHEA), a known synthetic and biocompatible polyamino acid, was used as a drug carrier, and Cytarabine was linked to PHEA by D-Val-Leu-Lys spacer synthesized beginning from Cbz-D-Val-LeuOH dipeptide and N6-CbzLys methyl ester. The content of Cytarabine in the purified PHEA-D-Val-Leu-Lys-Cytarabine conjugate was equal to 3% w/w. In vitro experiments in the presence of plasmin evidenced the ability of this enzyme to strongly increase drug release from the macromolecular prodrug, as well as plasma incubation shows high stability of drug-polymer linkage. The direct linkage of Cytarabine to PHEA was also performed and, like PHEA-D-Val-Leu-Lys-Cytarabine conjugate, the obtained PHEA-Cytarabine conjugate showed high stability in plasma, but no relea...Continue Reading

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Citations

Apr 25, 2003·Journal of Controlled Release : Official Journal of the Controlled Release Society·Gennara CavallaroStefano Salmaso
Mar 17, 2004·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·C GómezJ M Teijón
Mar 3, 2005·Journal of Neuroengineering and Rehabilitation·Peter T Gibbs, H Harry Asada
Dec 29, 2004·Journal of Drug Targeting·Gennara CavallaroGaetano Giammona
Mar 19, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Gianfranco PasutOddone Schiavon
Feb 3, 2007·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Weihua XueJunfeng Zhang
Jul 10, 2007·Journal of Biomedical Materials Research. Part a·G PitarresiG Giammona
Mar 13, 2010·Journal of Biomedical Materials Research. Part a·Vanangamudi AnbharasiSi-Shen Feng
Nov 17, 2004·Journal of Controlled Release : Official Journal of the Controlled Release Society·Pankaj V ParanjpePatrick J Sinko
Jun 23, 2004·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·G CavallaroG Giammona
Dec 5, 2006·International Journal of Pharmaceutics·G PitarresiF S Palumbo
Oct 10, 2006·Journal of Controlled Release : Official Journal of the Controlled Release Society·Gennara CavallaroGaetano Giammona
Nov 22, 2005·International Journal of Pharmaceutics·Gennara CavallaroGiammona Gaetano
Oct 20, 2005·Biomaterials·Mariano LicciardiGaetano Giammona
Dec 22, 2006·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Gennara CavallaroGaetano Giammona
Oct 3, 2008·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hiraku Onishi, Yoshiharu Machida
Oct 25, 2007·Journal of Biomedical Materials Research. Part a·Seung Rim YangJong-Duk Kim
Jul 8, 2005·Macromolecular Bioscience·Filippo SaianoGaetano Giammona
Mar 19, 2021·Chemical Society Reviews·Yufei XueNicolas Hans Voelcker

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