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

• Published in: Pharmaceutical research Vol. 28; no. 2; pp. 301 - 308
• Main Authors: Sawant, Rupa R, Vaze, Onkar, D'Souza, Gerard G. M, Rockwell, Karen, Torchilin, Vladimir P
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01.02.2011; Springer US; Springer Nature B.V
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Ascorbic Acid - analogs & derivatives; Ascorbic Acid - metabolism; Ascorbic Acid - pharmacology; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Cancer; Cell culture; Cell Line, Tumor; Cell Survival - drug effects; Cellular biology; Chelating Agents - metabolism; Coculture Techniques; Drug Carriers - chemistry; Female; Free Radical Scavengers - metabolism; Hydrogen Peroxide - chemistry; Inhibitory Concentration 50; Medical Law; Mice; Mice, Inbred BALB C; Micelles; Models, Animal; nanocarriers; neoplasms; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - pathology; NIH 3T3 Cells; palmitoyl ascorbate; Pharmacology/Toxicology; Pharmacy; Phosphatidylethanolamines - chemistry; Polyethylene glycol; Polyethylene Glycols - chemistry; Polymers; Reactive Oxygen Species; Research Paper; Rhodamines - chemistry; targeting; palmitoyl ascorbate; targeting; cancer; micelles; nanocarriers
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-010-0242-3

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.