Abstract
Objectives: The combination of 2 chemotherapeutic agents has been recommended in order to reduce their adverse side effects and potentiate their efficacy. The aim of the present study was to assess the antineoplastic activity of doxorubicin (DOX) combined with gemcitabine (GEM) in nanoemulsion (NE) against various cancer cells and to examine their adverse effects on the healthy human foreskin (HFS) cells.
Materials and Methods: The physical characterizations of the drug-loaded NE formulations were determined by Zetasizer. The cytotoxicity of the drugs was evaluated by the thiazolyl blue tetrazolium bromide (MTT) assay while the mechanism of cell death was examined by light microscopy, nuclear staining with 4',6-diamidino-2-phenylindole (DAPI) and ApopNexin FITC apoptosis detection kit.
Results: The Zetasizer results demonstrated that the nanoparticle of the combination of 5 mu M of DOX and GEM in NE (5DOX/5GEM-NE) has a particle size of 155.38 +/- 3.08 nm with a polydispersity index of 0.02 +/- 0.28 and a negative zeta potential of -7.70 +/- 1.30 mV. The 5DOX/5GEM-NE has decreased the percentages of HeLa cervical cancer cell viabilities to 27.00 +/- 5.62%, but it has not considerably changed the percentages of HFS cell viabilities (97.06 +/- 6.09%) when compared to the single treatments of DOX and GEM. According to the mechanism of cell death studies, 5DOX/5GEM-NE has induced apoptosis in HeLa cells without affecting the HFS cells.
Conclusions: The present study proved that formulating DOX and GEM in NE has ameliorated the efficacy of DOX and GEM as anticancer drugs while reducing their adverse effects on the healthy cells.