A nanoemulsion formulation of dacarbazine reduces tumor size in a xenograft mouse epidermoid carcinoma model compared to dacarbazine suspension

Dacarbazine (DAC) is an anticancer drug that has been used to treat various types of cancers. The aim of the current study was to test whether there is an increased efficacy of DAC as a nanoemulsion on reducing tumor size in an epidermoid carcinoma xenograft mouse model. Tumors were induced in 5-week-old nude mice by subcutaneous injection. The mice were untreated or treated with a suspension of DAC (0.1 mg/kg), a nanoemulsion of DAC (0.1 mg/kg), or Nano-Control (same composition as the suspension and nanoemulsion but no DAC), every 2 days by either intramuscular injection (IM) or topical application. After 40 days, the final tumor size of mice receiving the nanoemulsion of DAC IM (0.83 ± 0.55 mm3) was significantly reduced compared to the suspension of DAC IM (4.75 ± 0.49 mm3), Nano-Control IM (7.63 ± 0.91 mm3), and untreated (10.46 ± 0.06 mm3). The final tumor size of mice receiving the nanoemulsion of DAC topically (3.33 ± 0.63 mm3) was also significantly reduced compared to the suspension of DAC topically (7.64 ± 0.68 mm3). This increased efficacy maybe partially attributed to: 1) the reduced particle size of the nanoemulsion in comparison with suspension (111 versus > 6000 nm), 2) reduction in zeta potential of the nanoemulsion compared to suspension (−3.2 versus −89.1 mV), 3) production of a stable water dispersion relative to unstable suspension, 4) decreased polydispersity index of the nanoemulsion compared to suspension, and 5) greater stability of drug with the nanoemulsion in comparison with the suspension.From the Clinical EditorIn this clinically relevant study, the anti-tumor efficacy of dacarbazine was found to be significantly increased as a nanoemulsion in epidermoid carcinoma xenograft mice, both with IM and topical administration.

Graphical AbstractThe aim of the study was to test increased efficacy of dacarbazine (DAC) as a nanoemulsion on reducing tumor size in epidermoid carcinoma xenograft mice. The final tumor size of mice receiving the nanoemulsion of DAC IM was significantly reduced compared to suspension of DAC IM and the final tumor size of mice receiving the nanoemulsion of DAC topically was also significantly reduced compared to the suspension of DAC topically. This increased efficacy maybe partially attributed to reduced particle size and zeta potential, production of a stable water dispersion, decreased polydispersity index, and greater stability of drug with the nanoemulsion.Figure optionsDownload high-quality image (127 K)Download as PowerPoint slide