Novel diindolylmethane derivatives based NLC formulations to improve the oral bioavailability and anticancer effects in triple negative breast cancer
Novel diindolylmethane derivatives based NLC formulations to improve the oral bioavailability and anticancer effects in triple negative breast cancer
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DOI：
10.1016/j.ejpb.2016.08.006
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发表时间：
2016-11-01
影响因子：
4.9
通讯作者：
Singh, Mandip
中科院分区：
文献类型：
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作者：
Godugu, Chandraiah;Doddapaneni, Ravi;Singh, Mandip
本研究证明了新型C-取代二吲哚甲烷(DIM)衍生物DIM-10和DIM-14在侵袭性TNBC模型中具有良好的抗癌效果。体外研究表明，这些化合物具有很强的抗癌作用。药代动力学研究表明，Caco-2渗透性研究导致渗透性差，口服生物利用度低。制备纳米结构脂质载体(NLC)制剂以提高这些化合物的临床接受度。观察到NLC制剂的口服生物利用度显著增加。与DIM-10相比，DIM-10 NLC制剂的C-max和AUC分别增加了4.73倍和11.19倍。在DIM-14 NLC配方中也观察到了类似的增加模式。在犬体内，DIM-10 NLC制剂的C-max和AUC分别增加了2.65倍和2.94倍。在MDA-MB-231原位TNBC模型中的抗癌研究表明，在DIM-10和DIM-14 NLC处理的动物中，肿瘤体积显著减少。我们的研究表明，DIM-10和DIM-14的NLC公式在TNBC模型中是有效的。(C)2016年，由爱思唯尔出版。
The present study demonstrates the promising anticancer effects of novel C-substituted diindolylmethane (DIM) derivatives DIM-10 and DIM-14 in aggressive TNBC models. In vitro studies demonstrated that these compounds possess strong anticancer effects. Caco-2 permeability studies resulted in poor permeability and poor oral bioavailability was demonstrated by pharmacokinetic studies. Nano structured lipid carrier (NLC) formulations were prepared to increase the clinical acceptance of these compounds. Significant increase in oral bioavailability was observed with NLC formulations. Compared to DIM-10, DIM-10 NLC formulation showed increase in C-max and AUC values by 4.73 and 11.19-folds, respectively. Similar pattern of increase was observed with DIM-14 NLC formulations. In dogs DIM-10 NLC formulations showed an increase of 2.65 and 2.94-fold in C-max and AUC, respectively. The anticancer studies in MDA-MB-231 orthotopic TNBC models demonstrated significant reduction in tumor volumes in DIM-10 and DIM-14 NLC treated animals. Our studies suggest that NLC formulation of both DIM-10 and 14 is effective in TNBC models. (C) 2016 Published by Elsevier B.V.