Delivery of Apoptosis-inducing Piperine to Triple-negative Breast Cancer Cells via Co-polymeric Nanoparticles

Anticancer Res. 2020 Feb;40(2):689-694. doi: 10.21873/anticanres.13998.


Background/aim: Piperine, a major alkaloid of the fruit of black pepper plants, selectively inhibits the growth of triple-negative breast cancer cells but its lipophilicity restricts possible clinical application. This study therefore determined the feasibility of encapsulating piperine in nanoparticles (NPs) to increase its solubility in an aqueous environment.

Materials and methods: Piperine-loaded biodegradable methoxy poly(ethylene glycol)-poly(lactic-co-glycolic) acid copolymer-based NPs were produced by single emulsion solvent extraction and thin-film hydration. Growth and viability of triple-negative breast cancer (TNBC) cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Annexin-V-FLUOS/propidium iodide staining, respectively.

Results: Thin-film hydration was superior to single emulsion solvent extraction, yielding piperine-loaded NPs with an average size of 50 nm. Piperine-loaded NPs inhibited TNBC cell growth and induced apoptosis while sparing normal fibroblasts.

Conclusion: It is feasible to deliver a cytotoxic concentration of piperine to TNBC cells via NPs with the potential for improved bioavailability and solubility in biological fluids.

Keywords: Apoptosis; breast cancer; methoxy poly(ethylene glycol)-poly(lactic-co-glycolic) acid; piperine; thin-film hydration.

MeSH terms

  • Alkaloids / administration & dosage*
  • Alkaloids / chemistry
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / chemistry
  • Apoptosis / drug effects
  • Benzodioxoles / administration & dosage*
  • Benzodioxoles / chemistry
  • Cell Line, Tumor
  • Emulsions / administration & dosage
  • Emulsions / chemistry
  • Female
  • Humans
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Piperidines / administration & dosage*
  • Piperidines / chemistry
  • Polyesters / administration & dosage
  • Polyesters / chemistry
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / chemistry
  • Polyunsaturated Alkamides / administration & dosage*
  • Polyunsaturated Alkamides / chemistry
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / pathology


  • Alkaloids
  • Antineoplastic Agents, Phytogenic
  • Benzodioxoles
  • Emulsions
  • Piperidines
  • Polyesters
  • Polyunsaturated Alkamides
  • methoxypolyethyleneglycol-poly(lactic-co-glycolic acid)
  • Polyethylene Glycols
  • piperine