Antitumor activity of PEGylated biodegradable nanoparticles for sustained release of docetaxel in triple-negative breast cancer

Int J Pharm. 2014 Oct 1;473(1-2):55-63. doi: 10.1016/j.ijpharm.2014.06.058. Epub 2014 Jun 30.

Abstract

With the aim to find novel therapeutical approaches for triple-negative breast cancer (TNBC) treatment, we have developed a powder for i.v. injection based on cyclodextrins and docetaxel (DTX)-loaded polyethyleneglycol-poly(epsilon-caprolactone) nanoparticles (DTX-NPs). Nanoparticles are designed to concentrate at tumor level by enhanced permeability and retention effect and release drug cargo at a sustained rate in the blood and in tumor interstitium. DTX-NPs of around 70 nm, shielding proteins and allowing a sustained DTX release for about 30 days, were produced by melting sonication technique. DTX-NPs were associated to hydroxypropyl-β-cyclodextrin to give a powder for injection with excellent dispersibility and suitable for i.v. administration. DTX-NPs were as efficient as free DTX in inhibiting cell growth of MDA-MB231 cells, even at low concentrations, and displayed a comparable in vivo antitumor efficacy and better survival in a TNBC animal model as compared with DTX commercial formulation (Taxotere(®)). In conclusion, PEGylated biodegradable DTX-NPs highlighted their potential in the treatment of aggressive TNBC providing a foundation for future clinical studies.

Keywords: Docetaxel; PEGylated nanoparticles; Powder for injection; Sustained release; Triple-negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Blood Proteins / chemistry
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / chemistry
  • Docetaxel
  • Ethylene Glycols / chemistry*
  • Female
  • Humans
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mammary Neoplasms, Experimental / pathology
  • Mice, Nude
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Polyesters / chemistry*
  • Powders
  • Taxoids / administration & dosage*
  • Taxoids / chemistry
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / pathology
  • Tumor Burden / drug effects
  • beta-Cyclodextrins / chemistry

Substances

  • Antineoplastic Agents
  • Blood Proteins
  • Delayed-Action Preparations
  • Ethylene Glycols
  • Polyesters
  • Powders
  • Taxoids
  • beta-Cyclodextrins
  • poly(epsilon-caprolactone)-b-poly(ethylene glycol)
  • Docetaxel
  • 2-Hydroxypropyl-beta-cyclodextrin