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Pharmaceutical Research

, Volume 34, Issue 6, pp 1244–1254 | Cite as

Vitamin E-rich Nanoemulsion Enhances the Antitumor Efficacy of Low-Dose Paclitaxel by Driving Th1 Immune Response

  • Jun Ye
  • Wujun Dong
  • Yanfang Yang
  • Huazhen Hao
  • Hengfeng Liao
  • Bangyuan Wang
  • Xue Han
  • Yiqun Jin
  • Xuejun Xia
  • Yuling LiuEmail author
Research Paper

Abstract

Purpose

To overcome the drawbacks of high dose regimen and improve the outcomes of chemotherapy at a low dose, an immunotherapeutic nanoemulsion based combination of chemotherapeutic agent (paclitaxel) with immunomodulatory agent (vitamin E) was developed and evaluated for their antitumor effect against breast cancer.

Methods

A total of five nanoemulsions loaded with various content of vitamin E were prepared and characterized. The immunoregulatory effects of vitamin E along with the overall antitumor efficacy of vitamin E-rich nanoemulsion with a low dose of paclitaxel were investigated through in vitro and in vivo experiments.

Results

Vitamin E-rich nanoemulsion exhibited relatively narrow size distribution, high entrapment efficiency and controlled in vitro release profile. In RAW264.7 cells, vitamin E-rich nanoemulsion significantly enhanced the secretion of Th1 cytokines and down-regulated the secretion of Th2 cytokine. In a co-culture system, vitamin E-rich nanoemulsion induced a high apoptosis rate in MDA-MB-231 cells as compared with vitamin E-low nanoemulsion. Furthermore, vitamin E-rich nanoemulsion exhibited superior in vivo antitumor efficacy in comparison with Taxol and vitamin E-low nanoemulsion at a paclitaxel dose of 4 mg/kg.

Conclusions

Vitamin E-rich nanoemulsion has great potential for the treatment of breast cancers with a low dose of paclitaxel via driving Th1 immune response.

KEY WORDS

immunochemotherapy low-dose paclitaxel nanoemulsion Th1 immune response vitamin E 

Abbreviations

CFDA-SE

Carboxyfluorescein diacetate succinimidyl ester

EE

Entrapment efficiency

ELISA

Enzyme-linked immunosorbent assay

E:T

Effector cells: target cells

HPLC

High performance liquid chromatography

IFN-γ

Interferon γ

IL-10

Interleukin 10

IL-12

Interleukin 12

LDLR

Low-density lipoprotein receptor

MTD

Maximum tolerated dose

PBS

Phosphate buffer solution

PDI

Polydispersity index

PI

Propidium iodide

PTX

Paclitaxel

Th1

T helper 1

Th2

T helper 2

VE

Vitamin E

Notes

Acknowledgments and Disclosures

This work was financially supported by the National Natural Science Foundation of China (No. 81402874) and the Beijing Natural Science Foundation of China (No. 7162135). The authors report no conflicts of interest in this work.

Supplementary material

11095_2017_2141_Fig8_ESM.gif (37 kb)
Figure S1

The stability of nanoemulsions was monitored at 4°C for 9 months. (a) Particle size and polydispersity index (PDI) of nanoemulsions loaded with paclitaxel and variant content of vitamin E (0.01%, 2.4%, 4.8%, 7.2%, and 10%, w/v). (b) Particle size distribution and standard deviation of nanoemulsions determined by the Zeta Potential/Particle Sizer NICOMP 380 ZLS (PSS NICOMP, Santa Barbara, CA, USA). (GIF 37 kb)

11095_2017_2141_MOESM1_ESM.tif (6.7 mb)
High Resolution Image (TIFF 6904 kb)
11095_2017_2141_Fig9_ESM.gif (91 kb)
Figure S2

In vivo tumor growth inhibition (a) and body weight changes (b) of 4T1 tumor-bearing BALB/c nude mice after intravenous treatment of mice with Taxol, 0.01%VE, or 7.2%VE at the dose of 4 mg/kg PTX. (c) Representative images of excised tumors from different groups at the end of the experiment. a, 7.2%VE vs. Control, p < 0.01; b, 7.2%VE vs. Taxol, p < 0.01; c, 0.01%VE vs. Control, p < 0.01; d, 0.01%VE vs. Taxol, p < 0.01; e, 7.2%VE vs. 0.01%VE, p > 0.05. (GIF 91.1 kb)

11095_2017_2141_MOESM2_ESM.tif (8.6 mb)
High Resolution Image (TIFF 8.63 mb)

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Jun Ye
    • 1
    • 2
    • 3
  • Wujun Dong
    • 1
    • 2
  • Yanfang Yang
    • 1
    • 2
  • Huazhen Hao
    • 3
  • Hengfeng Liao
    • 1
    • 2
  • Bangyuan Wang
    • 1
    • 2
  • Xue Han
    • 3
  • Yiqun Jin
    • 3
  • Xuejun Xia
    • 1
    • 2
  • Yuling Liu
    • 1
    • 2
    Email author
  1. 1.State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia MedicaChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingPeople’s Republic of China
  2. 2.Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia MedicaChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingPeople’s Republic of China
  3. 3.Beijing Wehand-bio Pharmaceutical Co. Ltd.BeijingPeople’s Republic of China

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