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Self-assembled squalenoyl-cytarabine nanostructures as a potent nanomedicine for treatment of leukemic diseases
- Source :
- International Journal of Nanomedicine, Vol 2012, Iss default, Pp 2535-2546 (2012)
- Publication Year :
- 2012
- Publisher :
- Dove Medical Press, 2012.
-
Abstract
- Donato Cosco,1 Flavio Rocco,2 Maurizio Ceruti,2 Margherita Vono,1 Massimo Fresta,1,3 Donatella Paolino1,31Department of Health Sciences, University "Magna Græcia", Catanzaro; 2Dipartimento di Scienza e Tecnologia del Farmaco, Torino; 3UOC Farmacia Ospedaliera Fondazione per la Ricerca e la Cura dei Tumori "Tommaso Campanella", Campus Universitario "S Venuta", Catanzaro, ItalyBackground: In this investigation, the antileukemic activity of a new nanomedicine based on the conjugation of 1,1',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
- Subjects :
- Medicine (General)
R5-920
Subjects
Details
- Language :
- English
- ISSN :
- 11769114 and 11782013
- Volume :
- 2012
- Issue :
- default
- Database :
- Directory of Open Access Journals
- Journal :
- International Journal of Nanomedicine
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.308b47baed58469faf5a9c3ab927b8b0
- Document Type :
- article