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

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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.

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ACKNOWLEDGEMENTS

This research is based on a hypothesis originating with a proposal by Anthony R. Manganaro. Funding was provided by Anthony R. Manganaro. The authors gratefully acknowledge W.C. Hartner for his help in preparation of the research paper.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Mugar Building, Room 312, 360 Huntington Avenue, Boston, Massachusetts, 02115, USA

    Rupa R. Sawant, Onkar Vaze, Gerard G. M. D’Souza, Karen Rockwell & Vladimir P. Torchilin

  2. Department of Pharmaceutical Sciences, Massachusetts College of Pharmacy and Health Sciences, 179 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Gerard G. M. D’Souza

Authors
  1. Rupa R. Sawant
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  2. Onkar Vaze
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  4. Karen Rockwell
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  5. Vladimir P. Torchilin
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Correspondence to Vladimir P. Torchilin.

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Sawant, R.R., Vaze, O., D’Souza, G.G.M. et al. Palmitoyl Ascorbate-Loaded Polymeric Micelles: Cancer Cell Targeting and Cytotoxicity. Pharm Res 28, 301–308 (2011). https://doi.org/10.1007/s11095-010-0242-3

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  • DOI: https://doi.org/10.1007/s11095-010-0242-3

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