Evaluation of the in vitro activity and in vivo bioavailability of realgar nanoparticles prepared by cryo-grinding
Evaluation of the in vitro activity and in vivo bioavailability of realgar nanoparticles prepared by cryo-grinding
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DOI：
10.1016/j.ejps.2006.05.002
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发表时间：
2006-09-01
影响因子：
4.6
通讯作者：
Ho, Paul C.
中科院分区：
文献类型：
--
作者：
Wu, Jin-Zhu;Ho, Paul C.
三氧化二砷（As_2O_3）具有良好的抗肿瘤作用，特别是在白血病治疗中的应用前景，已成为研究的热点。另一种含砷化合物雄黄（As 2S 2）在古代中国和欧洲长期被用作治疗剂来治疗某些疾病，近年来其药用作用日益受到关注。然而，不幸的是，其较差的水溶性导致较差的生物利用度，并阻碍其被研究和用于可能的临床应用。本文以十二烷基硫酸钠（SDS）和聚乙烯吡咯烷酮（PVP）为原料，采用冷冻研磨法制备纳米雄黄。对纳米雄黄的主要物理性质进行了表征。雄黄与PVP和/或SDS共研磨产生更小和更单分散的纳米颗粒悬浮液。研究了这种纳米雄黄颗粒对选定的人卵巢癌（C180- 13 S，OVCAR，OVCAR-3）和宫颈癌（HeLa）细胞系的体外细胞毒性作用。观察到这些雄黄纳米颗粒对这些癌细胞系的显著的抗增殖作用。C180- 13 S对纳米雄黄颗粒最敏感，其IC 50值小于1 μ M，而其他癌细胞系的IC 50值在2-4 μ M的范围内。雄黄纳米颗粒对这些人妇科细胞系的细胞毒活性与先前观察到的三氧化二砷相当。在这些癌细胞系中，细胞周期和DNA梯状分析证实细胞毒性效应是由凋亡引起的。在体内研究中，观察到大鼠单次口服经冷冻研磨的雄黄颗粒混悬液后尿砷回收率显著增加。从PVP和/或SDS共研磨制剂的前48小时的尿中回收的砷剂量为58.5%至69.6%，而原雄黄粉的尿中回收率仅为24.9%。这一发现表明，将雄黄颗粒减小到纳米级可以大大提高其生物利用度。(c)2006 Elsevier B. V.保留所有权利。
Arsenic trioxide (As2O3) has been a research focus because of its promising anticancer effects especially in the treatment of leukemia. Another arsenic compound, realgar (As2S2), has long been used as a therapeutic agent to treat some diseases in ancient China and Europe, and its medicinal effects have attracted increasing attentions in recent years. However, its poor water-solubility unfortunately results in poor bio availability and hampers it from being studied and used for possible clinical application. in this study, nanosized realgar particles were prepared by cryo-grinding with polyvinylpyrrolidone (PVP) and/or sodium dodecyl sulfate (SDS). Major physical properties of the respective nanosized realgar particles were characterized. Co-grinding realgar with PVP and/or SDS produced smaller and more monodisperse suspension of nanoparticles. The in vitro cytotoxic effects of such nanosized realgar particles on selected human ovarian (C180-13S, OVCAR, OVCAR-3) and cervical (HeLa) cancer cell lines were investigated. Significant anti-proliferation effect of these realgar nanoparticles on these cancer cell lines was observed. C180-13S was most sensitive to the nanosized realgar particles with IC50 values of less than 1 mu M as As2S2, whereas the other cancer cell lines had IC50 values in a range of 2-4 mu M as As2S2. The cytotoxic activity of the realgar nanoparticles to these human gynecological cell lines was comparable to arsenic trioxide observed previously. in these cancer cell lines, the cytotoxic effects were caused by apoptosis as confirmed by cell cycle and DNA laddering analysis. In in vivo study, a remarkable increase in urinary recovery of arsenic was observed in rats after a single oral administration of the cryo-ground realgar particle suspension. Ranging from 58.5 to 69.6% of the administered dose of arsenic was recovered in urine in the first 48 h from the PVP and/or SDS co-ground preparations; whereas the original realgar powder gave a urinary recovery of only 24.9%. The finding suggested that size reduction of realgar particles to nano levels could enhance its biovailability substantially. (c) 2006 Elsevier B.V. All rights reserved.