Formulation-optimization of solid lipid nanocarrier system of STAT3 inhibitor to improve its activity in triple negative breast cancer cells

Drug Dev Ind Pharm. 2019 Feb;45(2):304-313. doi: 10.1080/03639045.2018.1539496. Epub 2018 Nov 8.

Abstract

In the present study, solid lipid nanoparticles (SLNs) have been formulated as a carrier system for effective intracellular delivery of STAT3 inhibitor, niclosamide (Niclo) to triple negative breast cancer (TNBC) cells. Emulsification-solvent evaporation method was employed in formulation of Niclo-loaded SLNs (Niclo-SLNs). The formula of Niclo-SLN was optimized by Box-Behnken design and characterized for their shape, size, and surface charge. The in vitro anti-cancer efficacy of Niclo-SLNs was studied in TNBC cells. The prepared Niclo-SLNs were found to be spherical with the particle size of 112.18 ± 1.73 nm and zetapotential of 23.8 ± 2.7 mV. In the in vitro anticancer study the Niclo SLNs show a better cytotoxicity than the naïve Niclo, which is attributed to improved cell uptake of SLN formulation. In conclusion, the results of the present study demonstrate that the formulation of Niclo as SLNs will improve the anticancer efficacy against TNBC.

Keywords: Breast cancer; MDA-MB231; STAT3; cell uptake; solid lipid nanocarriers.

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Survival
  • Drug Carriers
  • Drug Compounding
  • Emulsions
  • Female
  • Humans
  • Lipids / chemistry
  • Nanoparticles
  • Niclosamide / administration & dosage*
  • Niclosamide / pharmacokinetics
  • Niclosamide / pharmacology*
  • Particle Size
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / metabolism

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Emulsions
  • Lipids
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Niclosamide