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Vitamin E derivative-based multifunctional nanoemulsions for overcoming multidrug resistance in cancer

Nannan Zheng1, Yanan Gao1, Hongyu Ji2

  • 1a Department of Pharmaceutics, School of Pharmacy, Harbin Medical University , Harbin, PR China ;

Journal of Drug Targeting
|December 29, 2015
PubMed

Insights

This study developed Vitamin E-based nanoemulsions with paclitaxel to combat multidrug resistance (MDR) in ovarian cancer. The nanoemulsions enhanced drug efficacy by increasing intracellular drug levels and altering key protein expressions, offering a promising strategy against tumor chemotherapy resistance.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Research

Background:

  • Multidrug resistance (MDR) significantly hinders effective tumor chemotherapy.
  • Strategies are needed to overcome both intrinsic and acquired drug resistance.
  • Modulating Bax and Bcl-2 expression and P-gp transport function are key targets.

Purpose of the Study:

  • To develop Vitamin E derivative-based nanoemulsions containing paclitaxel (MNEs-PTX).
  • To evaluate the in vitro anticancer efficacy of MNEs-PTX in paclitaxel-resistant ovarian cancer cells.
  • To investigate the mechanisms by which MNEs-PTX overcomes multidrug resistance.

Main Methods:

  • Fabrication of Vitamin E derivative-based multifunctional nanoemulsions (MNEs) loaded with paclitaxel (PTX).
  • In vitro evaluation of MNEs-PTX antiproliferation effects on A2780/Taxol cells.
  • Assessment of mitochondrial potential, P-gp substrate accumulation (rhodamine 123), and Bax/Bcl-2 protein levels.

Main Results:

  • MNEs-PTX demonstrated significantly enhanced antiproliferation effects compared to free PTX in A2780/Taxol cells.
  • MNEs-PTX treatment led to decreased mitochondrial potential and increased intracellular accumulation of rhodamine 123.
  • MNEs reduced Bcl-2 protein levels and increased Bax protein levels, indicating modulation of apoptosis pathways.

Conclusions:

  • Vitamin E derivative-based nanoemulsions show potential in overcoming paclitaxel resistance in ovarian cancer.
  • The MNEs-PTX system effectively increases intracellular drug concentration and modulates key proteins involved in MDR.
  • This approach offers a promising strategy for developing novel therapeutics to combat multidrug resistance in cancer chemotherapy.
Keywords:
Bcl-2 family proteinsP-glycoproteinmultidrug resistancepaclitaxelvitamin E derivative-based multifunctional nanoemulsion

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