In vitro evaluation of antitumor activity of doxorubicin-loaded nanoemulsion in MCF-7 human breast cancer cells
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Doxorubicin (DOX) is an anticancer drug used to treat several cancer diseases. However, it has several dose limitation aspects because of its poor bioavailability, hydrophobicity, and cytotoxicity. In this study, five nanoemulsion (NE) formulations, containing soya phosphatidylcholine/polyoxyethylenglycerol trihydroxy-stearate 40 (EU)/sodium oleate as surfactant, cholesterol (CHO) as oil phase, and Tris–HCl buffer (pH 7.22), were produced. The NE droplets morphologies of the entire blank and DOX-loaded formulations, revealed by the transmission electron microscope, were spherical. The droplet sizes of blank NEs, obtained between 2.9 and 6.4 nm, decreased significantly with the increase in the ratio of surfactant-to-oil, whereas the droplets sizes of DOX-loaded NE formulations were significantly higher and found in the range of 7.7–15.9 nm. The evaluation for both blank and DOX-loaded NE formulations proved that the NE carrier had improved the DOX efficacy and reduced its cytotoxicity. It showed that the cell growth inhibition of the breast cancer cells (MCF-7) have exceeded the commercial DOX by a factor of 1.7 with increased apoptosis activity and minimal cytotoxicity against the normal human foreskin cells (HFS). In contrast, commercial DOX was found to exhibit a significant non-selective toxicity against both MCF-7 and HFS cells. In conclusion, we have developed DOX-loaded NE formulations which selectively and significantly inhibited cell proliferation of MCF-7 cells and increased apoptosis.
KeywordsCytotoxicity Sulphorhodamine B assay Apoptosis Transmission electron microscope
The authors wish to express a sincere thanks and appreciation to King Abdulaziz City for Science and Technology for its financial support to the research project designated by number (P-S-10-0016), King Abdulaziz University Hospital for providing cell cultures and King Fahd Medical Research Center, Jeddah, KSA, for technical support.
- Fornari FA, Jarvis WD, Grant S, Orr MS, Randolph JK, White FK, Mumaw VR, Lovings ET, Freeman RH, Gewirtz DA (1994) Induction of differentiation and growth arrest associated with nascent (non-oligosomal) DNA fragmentation and reduced c-myc expression in MCF-7 human breast tumor cells after continuous exposure to a sublethal concentration of doxorubicin. Cell Growth Differ 5:723–733Google Scholar
- Hurwitz E, Levy R, Maron R, Wilchek M, Arnon R, Sela M (1975) The covalent binding of daunomycin and adriamycin to antibodies, with retention of both drug and antibody activities. Cancer Res 35:1175–1181Google Scholar
- Ohkawa K, Hatano T, Yamada K, Joh K, Takada K, Tsukada Y, Matsuda M (1993) Bovine serum albumin-doxorubicin conjugate overcomes multidrug resistance in a rat hepatoma. Cancer Res 53:4238–4242Google Scholar
- Rapoport N, Nam K, Gupta R, Gao Z, Mohan P, Payne A, Todd N, Liu X, Kim T, Shea J, Scaife C, Parker DL, Jeong E, Kennedy AM (2011) Ultrasound-mediated tumor imaging and nanotherapy using drug loaded, block copolymer stabilized perfluorocarbon nanoemulsions. J Control Release 153:4–15CrossRefGoogle Scholar
- Talekar M, Ganta S, Singh A, Amiji M, Kendall J, Denny WA, Garg S (2010) Phosphatidylinositol 3-kinase inhibitor (PIK75) containing surface functionalized nanoemulsion for enhanced drug delivery, cytotoxicity and pro-apoptotic activity in ovarian cancer cells. Pharm Res 29:2874–2886CrossRefGoogle Scholar
- Venkateshwarlu I, Prabhakar K, Ali M, Kishan V (2010) Development and in vitro cytotoxic evaluation of parenteral docetaxel lipid nanoemulsions for application in cancer treatment. PDA J Pharm Sci Technol 64:233–241Google Scholar