Self-assembled squalenoyl-cytarabine nanostructures as a potent nanomedicine for treatment of leukemic diseases

Donato Cosco,1 Flavio Rocco,2 Maurizio Ceruti,2 Margherita Vono,1 Massimo Fresta,1,3 Donatella Paolino1,31Department of Health Sciences, University &quot;Magna Gr&aelig;cia&quot;, Catanzaro; 2Dipartimento di Scienza e Tecnologia del Farmaco, Torino; 3UOC Farmacia Ospedaliera...

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Autores principales:	Cosco D, Rocco F, Ceruti M, Vono M, Fresta M, Paolino D
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/308b47baed58469faf5a9c3ab927b8b0
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spelling	oai:doaj.org-article:308b47baed58469faf5a9c3ab927b8b02021-12-02T06:28:52ZSelf-assembled squalenoyl-cytarabine nanostructures as a potent nanomedicine for treatment of leukemic diseases1176-91141178-2013https://doaj.org/article/308b47baed58469faf5a9c3ab927b8b02012-05-01T00:00:00Zhttp://www.dovepress.com/self-assembled-squalenoyl-cytarabine-nanostructures-as-a-potent-nanome-a9950https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Donato Cosco,1 Flavio Rocco,2 Maurizio Ceruti,2 Margherita Vono,1 Massimo Fresta,1,3 Donatella Paolino1,31Department of Health Sciences, University &quot;Magna Gr&aelig;cia&quot;, Catanzaro; 2Dipartimento di Scienza e Tecnologia del Farmaco, Torino; 3UOC Farmacia Ospedaliera Fondazione per la Ricerca e la Cura dei Tumori &quot;Tommaso Campanella&quot;, Campus Universitario &quot;S Venuta&quot;, Catanzaro, ItalyBackground: In this investigation, the antileukemic activity of a new nanomedicine based on the conjugation of 1,1&#39;,2-tris-nor-squalenic acid with cytarabine (Ara-C) was evaluated.Methods: Squalenoyl-Ara-C conjugate (Sq-Ara-C) self-assembled nanosystems were obtained by the nanoprecipitation method and characterized in vitro and in vivo.Results: This new nanomedicine, which had a mean diameter of approximately 150 nm, improved the in vitro antitumoral activity of Ara-C in different cancer cell lines (L1210, K562, and MCF-7). Sq-Ara-C nanomedicine allowed reduction of the IC50 value with respect to the free drug and was also active against drug-resistant leukemic cells (L1210R). A noticeable increase in the survival rate of mice with aggressive metastatic L1210R leukemia was observed after treatment with Sq-Ara-C (50 mg/kg) as compared with the free active compound (100 mg/kg). Finally, evaluation of the biodistribution and pharmacokinetic profiles of the drug demonstrated that these nanoaggregates preferentially localized to the liver and spleen, and protected the drug from physiological metabolism.Conclusion: Squalenoylation of cytarabine offers several pharmacological benefits both in vitro and in vivo.Keywords: squalenoyl-cytarabine, self-assembly, antitumoral nanomedicine, leukemia, nanoaggregate, biodistributionCosco DRocco FCeruti MVono MFresta MPaolino DDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 2535-2546 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Cosco D Rocco F Ceruti M Vono M Fresta M Paolino D Self-assembled squalenoyl-cytarabine nanostructures as a potent nanomedicine for treatment of leukemic diseases
description	Donato Cosco,1 Flavio Rocco,2 Maurizio Ceruti,2 Margherita Vono,1 Massimo Fresta,1,3 Donatella Paolino1,31Department of Health Sciences, University &quot;Magna Gr&aelig;cia&quot;, Catanzaro; 2Dipartimento di Scienza e Tecnologia del Farmaco, Torino; 3UOC Farmacia Ospedaliera Fondazione per la Ricerca e la Cura dei Tumori &quot;Tommaso Campanella&quot;, Campus Universitario &quot;S Venuta&quot;, Catanzaro, ItalyBackground: In this investigation, the antileukemic activity of a new nanomedicine based on the conjugation of 1,1&#39;,2-tris-nor-squalenic acid with cytarabine (Ara-C) was evaluated.Methods: Squalenoyl-Ara-C conjugate (Sq-Ara-C) self-assembled nanosystems were obtained by the nanoprecipitation method and characterized in vitro and in vivo.Results: This new nanomedicine, which had a mean diameter of approximately 150 nm, improved the in vitro antitumoral activity of Ara-C in different cancer cell lines (L1210, K562, and MCF-7). Sq-Ara-C nanomedicine allowed reduction of the IC50 value with respect to the free drug and was also active against drug-resistant leukemic cells (L1210R). A noticeable increase in the survival rate of mice with aggressive metastatic L1210R leukemia was observed after treatment with Sq-Ara-C (50 mg/kg) as compared with the free active compound (100 mg/kg). Finally, evaluation of the biodistribution and pharmacokinetic profiles of the drug demonstrated that these nanoaggregates preferentially localized to the liver and spleen, and protected the drug from physiological metabolism.Conclusion: Squalenoylation of cytarabine offers several pharmacological benefits both in vitro and in vivo.Keywords: squalenoyl-cytarabine, self-assembly, antitumoral nanomedicine, leukemia, nanoaggregate, biodistribution
format	article
author	Cosco D Rocco F Ceruti M Vono M Fresta M Paolino D
author_facet	Cosco D Rocco F Ceruti M Vono M Fresta M Paolino D
author_sort	Cosco D
title	Self-assembled squalenoyl-cytarabine nanostructures as a potent nanomedicine for treatment of leukemic diseases
title_short	Self-assembled squalenoyl-cytarabine nanostructures as a potent nanomedicine for treatment of leukemic diseases
title_full	Self-assembled squalenoyl-cytarabine nanostructures as a potent nanomedicine for treatment of leukemic diseases
title_fullStr	Self-assembled squalenoyl-cytarabine nanostructures as a potent nanomedicine for treatment of leukemic diseases
title_full_unstemmed	Self-assembled squalenoyl-cytarabine nanostructures as a potent nanomedicine for treatment of leukemic diseases
title_sort	self-assembled squalenoyl-cytarabine nanostructures as a potent nanomedicine for treatment of leukemic diseases
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/308b47baed58469faf5a9c3ab927b8b0
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Self-assembled squalenoyl-cytarabine nanostructures as a potent nanomedicine for treatment of leukemic diseases

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