In vitro suppression of oral squamous cell carcinoma growth by ultrasound-mediated delivery of curcumin microemulsions

Hung-Yin Lin1,2, James L Thomas3, Huan-Wen Chen1, Chih-Min Shen4, Wen-Jen Yang2, Mei-Hwa Lee41Department of Chemical and Materials Engineering, National University of Kaohsiung, Kaohsiung, Taiwan; 2Institute of Biotechnology, National University of Kaohsiung, Kaohsiung, Taiwan; 3Department of Physics and Astronomy, University of New Mexico, Albuquerque, NM; 4Department of Materials Science and Engineering, I-Shou University, Kaohsiung, TaiwanAbstract: There is increasing interest in using natural products as anticancer agents, as many have antioxidative properties that may help to prevent cellular damage that can lead to cancer. In addition, there is the expectation that many natural products will have low toxicity and few side effects. However, most anticancer and antioxidative agents are hydrophobic, reducing their bioavailability in vivo and making them problematic to deliver. Curcumin provides a good model system for study. In low doses it shows both anticancer and antioxidation effects, whereas in high doses and delivered locally it could be cytotoxic for cancer cells. In this paper, curcumin microemulsions were formed with food-grade chemicals, including soybean lecithin, soybean oil, and Tween 80, a Food and Drug Administration-approved surfactant. The optimized composition formed curcumin microemulsions with a mean size of 40–50 nm, carrying a concentration of curcumin as high as 15 µM. The stability of curcumin microemulsions refrigerated at 5°C over at least 968 days was assessed by size distribution and zeta potential. The effects of low-frequency ultrasound on two oral squamous cell carcinoma cell lines (OSCC-4 and OSCC-25), and the synergy between treatment with curcumin microemulsions and low-frequency sonic stimulation, were tested. Finally, microscopic imaging of the cells confirmed the toxic effects of the curcumin microemulsions, showing damaged and ruptured cells after treatment. Brief exposure to the curcumin-containing microemulsions did have cytotoxic effects, but the addition of ultrasound strongly enhanced those effects, especially on OSCC-25 cells.Keywords: oral squamous cell carcinoma (OSCC), curcumin, microemulsion, ultrasound, controlled releas