Pharmaceutical Research

, Volume 28, Issue 2, pp 301–308

Palmitoyl Ascorbate-Loaded Polymeric Micelles: Cancer Cell Targeting and Cytotoxicity

  • Rupa R. Sawant
  • Onkar Vaze
  • Gerard G. M. D’Souza
  • Karen Rockwell
  • Vladimir P. Torchilin
Research Paper

ABSTRACT

Purpose

To evaluate the potential of palmitoyl ascorbate (PA)-loaded micelles for ascorbate-mediated cancer cell targeting and cytotoxicity.

Methods

PA was incorporated in polyethylene glycol-phosphatidyl ethanolamine micelles at varying concentrations. The formulations were evaluated for PA content by RP-HPLC. A stable formulation was selected based on size and zeta potential measurements. A co-culture of cancer cells and GFP-expressing non-cancer cells was used to determine the specificity of PA micelle binding. In vitro cytotoxicity of the micellar formulations towards various cancer cell lines was investigated using a cell viability assay. To elucidate the mechanism of action of cell death in vitro, the effect of various H2O2 scavengers and metal chelators on PA-mediated cytotoxicity was studied. The in vivo anti-cancer activity of PA micelles was studied in female Balb/c mice bearing a murine mammary carcinoma (4T1 cells).

Results

PA micelles associated preferentially with various cancer cells compared to non-cancer cells in co-culture. PA micelles exhibited anti-cancer activity in cancer cell lines both in vitro and in vivo. The mechanism of cell death was due primarily to generation of reactive oxygen species (ROS).

Conclusions

The anti-cancer activity of PA micelles associated with its enhanced cancer cell binding and subsequent generation of ROS.

KEY WORDS

cancer micelles nanocarriers palmitoyl ascorbate targeting 

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Rupa R. Sawant
    • 1
  • Onkar Vaze
    • 1
  • Gerard G. M. D’Souza
    • 1
    • 2
  • Karen Rockwell
    • 1
  • Vladimir P. Torchilin
    • 1
  1. 1.Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and NanomedicineNortheastern UniversityBostonUSA
  2. 2.Department of Pharmaceutical SciencesMassachusetts College of Pharmacy and Health SciencesBostonUSA

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