Delivery of acetylthevetin B, an antitumor cardiac glycoside, using polymeric micelles for enhanced therapeutic efficacy against lung cancer cells

Acetylthevetin B （ATB）, a cardiac glycoside from the seed of Thevetia peruviana （Pers） K Schum （yellow oleander）, exhibits not only antitumor activity but also potential cardiac toxicity. In the present study, we attempted to enhance its antitumor action and decrease its adverse effects via chitosan...

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Bibliographic Details
Published in:Acta pharmacologica Sinica 2017-02, Vol.38 (2), p.290-300
Main Authors: Zhu, Jing-Jing, Zhang, Xin-Xin, Miao, Yun-Qiu, He, Shu-Fang, Tian, Dan-Mei, Yao, Xin-Sheng, Tang, Jin-Shan, Gan, Yong
Format: Article
Language:English
Subjects:
Animals
Cardiac Glycosides - administration & dosage
Cardiac Glycosides - pharmacology
Cardiac Glycosides - therapeutic use
Cell Line, Tumor
Chitosan - chemistry
Drug Carriers - chemistry
Humans
Lung cancer
Mice
Micelles
Nerium oleander
Original
Particle Size
Poloxalene - chemistry
Thevetia peruviana
Xenograft Model Antitumor Assays
交货
强心苷
抗癌
抗肿瘤作用
抗肿瘤活性
疗效
聚合物胶束
肺癌细胞
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Summary:Acetylthevetin B （ATB）, a cardiac glycoside from the seed of Thevetia peruviana （Pers） K Schum （yellow oleander）, exhibits not only antitumor activity but also potential cardiac toxicity. In the present study, we attempted to enhance its antitumor action and decrease its adverse effects via chitosan-Pluronic P123 （CP） micelle encapsulation. Two ATB- loaded CP micelles （ATB-CP1, ATS-CP2） were prepared using an emulsion/solvent evaporation technique. They were spherical in shape with a particle size of 40-50 rim, showed a neutral zeta potential, and had acceptable encapsulation efficiency （〉90%）. Compared to the free ATB （IC50=2.94 μmol/L）, ATB-loaded CP micelles exerted much stronger cytotoxicity against human lung cancer A549 cells with lower IC50 values （0.76 and 1.44 μmol/L for ATB-CP1 and ATB-CP2, respectively）. After administration of a single dose in mice, the accumulation of ATB-ioaded CP1 micelles in the tumor and lungs, respectively, was 15.31-fold and 9.49-fold as high as that of free ATB. A549 xenograft tumor mice treated with ATB- loaded CP1 micelles for 21 d showed the smallest tumor volume （one-fourth of that in the control group） and the highest inhibition rate （85.6%） among all the treatment groups. After 21-d treatment, no significant pathological changes were observed in hearts and other main tissues. In summary, AT8 may serve as a promising antitumor chemotherapeutic agent for lung cancer, and its antitumor efficacy was significantly improved by CP micelles, with lower adverse effects.
ISSN:1671-4083
1745-7254
DOI:10.1038/aps.2016.113