A novel self-nanoemulsifying formulation for sunitinib: Evaluation of anticancer efficacy

Colloids Surf B Biointerfaces. 2017 Dec 1:160:65-72. doi: 10.1016/j.colsurfb.2017.09.008. Epub 2017 Sep 7.

Abstract

Breast cancer is the top cancer and a main cause of death among women. The incidence of this cancer is increasing in the world. Sunitinib maleate is an oral, small-molecule, multi-targeted receptor tyrosine kinase inhibitor that inhibits tumor cell proliferation and angiogenesis, and has been administrated as an anticancer drug. Self-nanoemulsifying drug delivery system (SNEDDS) is an isotopic mixture of an oil, a surfactant and usually a co-surfactant, which can spontaneously form fine oil-in-water nanoemulsion in aqueous media. Here, a SNEDDS composed of 15% ethyl oleate (as an oil phase), 30% tween 80 (as a surfactant), and 55% PEG 600 (as a co-surfactant) was prepared and developed as a carrier for sunitinib. The average droplet size of sunitinib-loaded SNEDDS was 29.5±6.3nm with a stability of more than one month. Sunitinib release from SNEDDS was enhanced accompanied by a controlled dissolution of the drug. Cytotoxicity studies on 4T1 and MCF-7 cell lines indicated a toxicity enhancement in sunitinib by SNEDDS. To inspect the bioavailability of the drug-loaded SNEDDS after oral administration with a dose of 50mgkg-1, the maximum plasma concentration and the mean area under the plasma concentration-time curve were measured. It was found that these parameters were increased 1.45- and 1.24-times respectively, compared to a drug suspension.

Keywords: Bioavailability; Drug delivery; Emulsion; Sutent(®).

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Delivery Systems / methods*
  • Drug Liberation
  • Emulsions / chemistry*
  • Humans
  • Indoles / administration & dosage*
  • Indoles / chemistry
  • Indoles / pharmacokinetics
  • MCF-7 Cells
  • Male
  • Mice
  • Nanoparticles / chemistry*
  • Particle Size
  • Pyrroles / administration & dosage*
  • Pyrroles / chemistry
  • Pyrroles / pharmacokinetics
  • Rats, Sprague-Dawley
  • Sunitinib
  • Tissue Distribution

Substances

  • Antineoplastic Agents
  • Emulsions
  • Indoles
  • Pyrroles
  • Sunitinib