Palmitoyl Ascorbate-Loaded Polymeric Micelles: Cancer Cell Targeting and Cytotoxicity
ABSTRACT PurposeTo evaluate the potential of palmitoyl ascorbate (PA)-loaded micelles for ascorbate-mediated cancer cell targeting and cytotoxicity.
MethodsPA 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).
ResultsPA 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).
ConclusionsThe anti-cancer activity of PA micelles associated with its enhanced cancer cell binding and subsequent generation of ROS.
KEY WORDScancer–micelles–nanocarriers–palmitoyl ascorbate–targeting
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ABSTRACT: Drug nanoparticle formulation using ascorbic acid derivatives and its therapeutic uses have recently been introduced. Hydrophilic ascorbic acid derivatives such as ascorbyl glycoside have been used not only as antioxidants but also as food and pharmaceutical excipients. In addition to drug solubilization, drug nanoparticle formation was observed using ascorbyl glycoside. Hydrophobic ascorbic acid derivatives such as ascorbyl mono- and di-n-alkyl fatty acid derivatives are used either as drugs or carrier components. Ascorbyl n-alkyl fatty acid derivatives have been formulated as antioxidants or anticancer drugs for nanoparticle formulations such as micelles, microemulsions, and liposomes. ASC-P vesicles called aspasomes are submicron-sized particles that can encapsulate hydrophilic drugs. Several transdermal and injectable formulations of ascorbyl n-alkyl fatty acid derivatives were used, including ascorbyl palmitate.Journal of drug delivery. 01/2011; 2011:138929.