Nanoformulation of D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) diblock copolymer for breast cancer therapy

Integr Biol (Camb). 2011 Oct;3(10):993-1002. doi: 10.1039/c1ib00026h. Epub 2011 Sep 22.

Abstract

The purpose of this research was to develop formulation of docetaxel-loaded biodegradable TPGS-b-(PCL-ran-PGA) nanoparticles for breast cancer chemotherapy. A novel diblock copolymer, d-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) [TPGS-b-(PCL-ran-PGA)], was synthesized from ε-caprolactone, glycolide and d-α-tocopheryl polyethylene glycol 1000 succinate by ring-opening polymerization using stannous octoate as catalyst. The obtained copolymers were characterized by (1)H NMR, GPC and TGA. The docetaxel-loaded TPGS-b-(PCL-ran-PGA) nanoparticles were prepared and characterized. The data showed that the fluorescence TPGS-b-(PCL-ran-PGA) nanoparticles could be internalized by MCF-7 cells. The TPGS-b-(PCL-ran-PGA) nanoparticles achieved significantly higher level of cytotoxicity than commercial Taxotere®. MCF-7 xenograft tumor model on SCID mice showed that docetaxel formulated in the TPGS-b-(PCL-ran-PGA) nanoparticles could effectively inhibit the growth of tumor over a longer period of time than Taxotere® at the same dose. In conclusion, the TPGS-b-(PCL-ran-PGA) copolymer could be acted as a novel and potential biologically active polymeric material for nanoformulation in breast cancer chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Breast Neoplasms / drug therapy*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Docetaxel
  • Female
  • Humans
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mice, SCID
  • Microscopy, Electron, Scanning
  • Nanoparticles / chemistry
  • Nanoparticles / therapeutic use*
  • Nanoparticles / ultrastructure
  • Polyesters / administration & dosage
  • Polyesters / chemistry*
  • Polyethylene Glycols / chemistry
  • Polyglycolic Acid / chemistry
  • Random Allocation
  • Taxoids / administration & dosage*
  • Taxoids / chemistry*
  • Vitamin E / analogs & derivatives*
  • Vitamin E / chemistry
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Polyesters
  • Taxoids
  • Vitamin E
  • Docetaxel
  • polycaprolactone
  • Polyglycolic Acid
  • Polyethylene Glycols
  • tocophersolan