Improved safety and efficacy of a lipid emulsion loaded with a paclitaxel-cholesterol complex for the treatment of breast tumors

Ye,Jun; Liu,Yuling; Xia,Xuejun; Meng,Luhua; Dong,Wujun; Wang,Renyun; Fu,Zhaodi; Liu,Hongyan; Han,Rui

doi:10.3892/or.2016.4787

Improved safety and efficacy of a lipid emulsion loaded with a paclitaxel-cholesterol complex for the treatment of breast tumors

Authors:
- Jun Ye
- Yuling Liu
- Xuejun Xia
- Luhua Meng
- Wujun Dong
- Renyun Wang
- Zhaodi Fu
- Hongyan Liu
- Rui Han
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Affiliations: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. China
Published online on: May 6, 2016 https://doi.org/10.3892/or.2016.4787
Pages: 399-409

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Abstract

The aim of the present study was to develop a lipid emulsion loaded with a paclitaxel-cholesterol complex (PTX-CH Emul) in order to improve the safety and efficacy of paclitaxel (PTX) and evaluate its antitumor activity against commercially available formulation Taxol®. PTX-CH Emul resembling a low density lipoprotein lipid structure, exhibited an ideal particle size, high drug loading capability, high drug encapsulation efficiency and excellent stability. PTX-CH Emul showed superior in vitro anticancer efficacy against triple-negative MDA-MB-231 breast cancer cells when compared with a paclitaxel emulsion (PTX Emul) and Taxol. The IC70 value of PTX-CH Emul was almost 1.5- and 2.4-fold lower than that of PTX Emul and Taxol, respectively. Compared with PTX Emul and Taxol, PTX-CH Emul exhibited stronger and more rapid inhibitory effects on 3D tumor spheroids of MDA-MB-231 cells. Additionally, in vivo tumor-targeting study showed that PTX-CH Emul had higher specificity and efficiency in intratumoral accumulation as compared to PTX Emul. Finally, the maximum tolerated dose (MTD) of PTX-CH Emul was 2.25‑fold higher than that of Taxol, suggesting that PTX-CH Emul exhibited better safety profiles in vivo than Taxol. At the MTDs, PTX-CH Emul exhibited superior antitumor efficacy in nude mice bearing MDA-MB-231 xenografts in comparison to Taxol. Therefore, PTX-CH Emul as reported here showed high potential as a drug carrier for PTX in clinical applications involving the targeting of triple-negative breast cancer.

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