Development of idarubicin and doxorubicin solid lipid nanoparticles to overcome Pgp-mediated multiple drug resistance in leukemia.
Development of idarubicin and doxorubicin solid lipid nanoparticles to overcome Pgp-mediated multiple drug resistance in leukemia.
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DOI：
10.1166/jbn.2009.1021
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发表时间：
2009-04
影响因子：
2.9
通讯作者：
Mumper RJ
中科院分区：
文献类型：
--
作者：
Ma P;Dong X;Swadley CL;Gupte A;Leggas M;Ledebur HC;Mumper RJ
这些研究的目的是研究和比较两种蒽环类药物伊达比星(IDA)和阿霉素(DOX)的固体脂质纳米粒(SLN)对Pgp介导的多药耐药(MDR)的影响。使用不同的人和小鼠癌细胞模型进行体外和体内实验。以乳化蜡为油相，聚氧基20-硬脂基醚(Brij78)和D-α-生育酚聚乙二醇丁二酸酯(Vitamin E TPGS)为表面活性剂的温微乳液前驱体制备了IDA和DOX SLN。用阴离子配对试剂牛磺酸脱氧胆酸钠(STDC)和十四烷基硫酸钠(STS)中和阳离子蒽环类药物的电荷，提高药物在SLN中的包封率。体外细胞毒性实验结果表明，DOX纳米粒对耐药细胞株P388/ADR的IC50值比游离DOX溶液低9倍。相反，在Pgp过表达的P388/ADR和HCT-15细胞中，游离IDA与IDA NPs具有相似的IC50值。在体内P388/ADR白血病小鼠模型中，DOX纳米粒的中位存活时间显著长于游离DOX组和对照组。相反，在P388和Pgp过表达的HCT-15小鼠肿瘤模型中，游离IDA与IDA NPs同样有效。在Pgp过表达的细胞中，作为游离IDA和IDA NPs的IDA的细胞摄取是相似的。综上所述，DOX纳米粒在P388/ADR白血病细胞体内和小鼠白血病模型中均能克服Pgp介导的多药耐药。本研究提示，我们的SLN可能为治疗Pgp介导的白血病多药耐药提供潜在的抗癌药物，但靶向药物的选择可能是非常重要的。
The objectives of these studies were to investigate and compare solid lipid nanoparticles (SLNs) of two anthracyclines, idarubicin (IDA) and doxorubicin (DOX), against Pgp-mediated multiple drug resistance (MDR.) in-vitro and in-vivo using different human and murine cancer cell models. IDA and DOX SLNs were developed from warm microemulsion precursors comprising emulsifying wax as the oil phase, and polyoxyl 20-stearyl ether (Brij 78) and D-alpha-tocopheryl polyethylene glycol succinate (Vitamin E TPGS) as the surfactants. Anionic ion-pairing agents, sodium taurodeoxycholate (STDC) and sodium tetradecyl sulfate (STS), were used to neutralize the charges of the cationic anthracyclines and enhance entrapment of the drugs in the SLN. The in-vitro cytotoxicity results showed that the IC50 value of DOX NPs was 9-fold lower than that of free DOX solution in resistant P388/ADR cell line. In contrast, free IDA had comparable IC50 values as IDA NPs in Pgp-overexpressing P388/ADR and HCT-15 cells. In the in-vivo P388/ADR leukemia mouse model, the median survival time of DOX NPs was significantly greater than that of free DOX, and controls. In contrast, free IDA was equally as effective as IDA NPs in P388 and Pgp-overexpressing HCT-15 mouse tumor models. The cell uptake of IDA formulated as free IDA and IDA NPs was comparable in Pgp-overexpressing cells. In conclusion, DOX NPs could overcome Pgp-mediated MDR both in-vitro in P388/ADR leukemia cells and in-vivo in the murine leukemia mouse model. The present study suggests that our SLNs may offer potential to deliver anticancer drugs for the treatment of Pgp-mediated MDR in leukemia; however, selection of target drug may be very important.
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DOI：
10.1016/s0167-4889(99)00060-9
发表时间：
1999-07-08
影响因子：
5.1
作者：
Marbeuf-Gueye, C;Ettori, D;Garnier-Suillerot, A
通讯作者：
Garnier-Suillerot, A
影响因子：
3.4
作者：
Gallois, L;Fiallo, M;Garnier-Suillerot, A
通讯作者：
Garnier-Suillerot, A
影响因子：
10.8
作者：
Oyewumi, MO;Yokel, RA;Mumper, RJ
通讯作者：
Mumper, RJ
影响因子：
3.6
作者：
Marbeuf-Gueye, C;Broxterman, HJ;Garnier-Suillerot, A
通讯作者：
Garnier-Suillerot, A
影响因子：
5
作者：
Zahraei, Zohreh;Rabbani-Chadegani, Azra
通讯作者：
Rabbani-Chadegani, Azra