Preparation of arsenic trioxide-loaded microemulsion and its enhanced cytotoxicity on MCF-7 breast carcinoma cell line

Drug Deliv. 2004 Nov-Dec;11(6):345-50. doi: 10.1080/10717540490494096.

Abstract

In this study, an injectable microemulsion of arsenic trioxide (As2O3-M) was prepared for intratumoral injection and the suppressive effect of As2O3-loaded microemulsion on human breast cancer cells MCF-7 was compared with those of a solution of the drug. Microemulsion was made up of soybean oil as oil phase, a mixture of Brij 58 and Span 80 as surfactants, absolute ethanol as cosurfactant, and bidistilled water containing As2O3 solution as the aqueous phase. Microemulsion formulation contains 5 x 10(-6) M As2O3. The pH of As2O3-M was adjusted to 7.35 +/- 0.1 and the physicochemical stability of the formulation was observed. The particle size distribution and zeta potential of As2O3-M were measured by Zetasizer 3000 HSA. The mean droplet diameters of As2O3-M were determined as 8.6 +/- 0.4 nm. As2O3-M exhibited 13.1 +/- 0.9 mV zeta potential. The formulation was physically stable for 12 months at room temperature when kept in ampule forms, as well as after autoclaving at 110 degrees C for 30 min. The antitumor effects of As2O3-M were examined on human breast cancer cells MCF-7. It was clearly demonstrated that As2O3-M had a significant cytotoxic effect on breast cancer cell lines, and the cytotoxic effect of As2O3-M was significantly more than that of regular As2O3 solutions. Even approximately 3000 times diluted microemulsion formulation loaded with 5 x 10(-6) M As2O3 showed a cytotoxic effect. As a result, this diluted concentration (approximately 1.6 x 10(-9) M) was found 1000 times more effective than regular As2O3 solutions (5 x 10(-6) M). According to the in vitro cytotoxicity studies, we concluded that when As2O3 was incorporated into the microemulsion (As2O3-M), which is a new drug carrier system, it suppresses tumor cell growth on multiple tumor lines. These results indicate that As2O3-M may exert a low cytotoxic effect on normal cells and may be effective as an antitumor agent that induces apoptosis.

MeSH terms

  • Arsenic Trioxide
  • Arsenicals / administration & dosage
  • Arsenicals / chemical synthesis*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemical synthesis*
  • Drug Carriers / toxicity*
  • Emulsions
  • Humans
  • Injections, Intralesional
  • Oxides / administration & dosage
  • Oxides / chemical synthesis*
  • Oxides / toxicity*
  • Particle Size

Substances

  • Arsenicals
  • Drug Carriers
  • Emulsions
  • Oxides
  • Arsenic Trioxide