自组装鲨烯酰阿糖胞苷纳米结构作为治疗白血病疾病的有效纳米药物。

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 IC(50) 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.

背景

在这项研究中，评估了基于 1,1',2-三去甲-squalenic 酸与阿糖胞苷（Ara-C）缀合的新型纳米医学的抗白血病活性。

方法

通过纳米沉淀法获得了 squalenoyl-Ara-C 缀合物（Sq-Ara-C）自组装纳米系统，并对其进行了体外和体内表征。

结果

这种新的纳米医学药物的平均直径约为 150nm，提高了不同癌细胞系（L1210、K562 和 MCF-7）中 Ara-C 的体外抗肿瘤活性。Sq-Ara-C 纳米药物降低了与游离药物相比的 IC50 值，并且对耐药性白血病细胞（L1210R）也具有活性。与游离活性化合物（100mg/kg）相比，用 Sq-Ara-C（50mg/kg）治疗侵袭性转移性 L1210R 白血病小鼠后，观察到生存率明显提高。最后，药物的体内分布和药代动力学评价表明，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的影响。