Self-assembled squalenoyl-cytarabine nanostructures as a potent nanomedicine for treatment of leukemic diseases.
Self-assembled squalenoyl-cytarabine nanostructures as a potent nanomedicine for treatment of leukemic diseases.
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DOI：
10.2147/ijn.s28114
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发表时间：
2012
影响因子：
8
通讯作者：
Paolino D
中科院分区：
文献类型：
--
作者：
Cosco D;Rocco F;Ceruti M;Vono M;Fresta M;Paolino D
在这项研究中，评估了一种基于 1,1',2-三去甲角鲨烯酸与阿糖胞苷 (Ara-C) 结合的新型纳米药物的抗白血病活性。通过纳米沉淀法获得了角鲨烯酰-Ara-C缀合物（Sq-Ara-C）自组装纳米系统，并进行了体外和体内表征。这种平均直径约为 150 nm 的新型纳米药物提高了 Ara-C 在不同癌细胞系（L1210、K562 和 MCF-7）中的体外抗肿瘤活性。 Sq-Ara-C 纳米药物可以降低游离药物的 IC50 值，并且对耐药白血病细胞 (L1210R) 也有活性。与游离活性化合物（100 mg/kg）相比，用 Sq-Ara-C（50 mg/kg）治疗后，观察到患有侵袭性转移性 L1210R 白血病的小鼠的存活率显着增加。最后，对药物生物分布和药代动力学特征的评估表明，这些纳米聚集体优先定位于肝脏和脾脏，并保护药物免受生理代谢影响。阿糖胞苷的角鲨烯酰化在体外和体内均具有多种药理学益处。
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. Squalenoyl-Ara-C conjugate (Sq-Ara-C) self-assembled nanosystems were obtained by the nanoprecipitation method and characterized in vitro and in vivo. 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. Squalenoylation of cytarabine offers several pharmacological benefits both in vitro and in vivo.