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

Authors Cosco D, Rocco F, Ceruti M, Vono M, Fresta M, Paolino D

Received 10 November 2011

Accepted for publication 11 February 2012

Published 23 May 2012 Volume 2012:7 Pages 2535—2546

DOI https://doi.org/10.2147/IJN.S28114

Review by Single-blind

Peer reviewer comments 3

Donato Cosco,1 Flavio Rocco,2 Maurizio Ceruti,2 Margherita Vono,1 Massimo Fresta,1,3 Donatella Paolino1,3

1Department 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, Italy

Background: 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

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