Palmitoyl Ascorbate-Loaded Polymeric Micelles: Cancer Cell Targeting and Cytotoxicity
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- Sawant, R.R., Vaze, O., D’Souza, G.G.M. et al. Pharm Res (2011) 28: 301. doi:10.1007/s11095-010-0242-3
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To evaluate the potential of palmitoyl ascorbate (PA)-loaded micelles for ascorbate-mediated cancer cell targeting and cytotoxicity.
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).
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).
The anti-cancer activity of PA micelles associated with its enhanced cancer cell binding and subsequent generation of ROS.