Star-shaped polymer of β‑cyclodextrin-g-vitamin E TPGS for doxorubicin delivery and multidrug resistance inhibition

Colloids Surf B Biointerfaces. 2018 Sep 1:169:10-19. doi: 10.1016/j.colsurfb.2018.05.001. Epub 2018 May 1.

Abstract

Multidrug resistance (MDR) remains as an obstacle for effective cancer treatment. Herein, we developed a novel and efficient nanomedicine by virtue of the carrier characters and MDR inhibition effects of β-cyclodextrin (β-CD) and d-α-tocopheryl polyethylene glycol succinate (TPGS). A series of star-shaped polymers CD-g-TPGS with different TPGS substitution degree were synthesized for doxorubicin (DOX) delivery, where β-CD was identified as a core and TPGS as branches. These star polymers can self-assemble into nanoparticles with DOX. These nanoparticles showed no significant differences in size, zeta potential and morphology except for in vitro stability. They demonstrated good biocompatibility and enhanced cellular uptake in both drug sensitive and resistant cancer cells. Notably, the nanoparticles exhibited superiority of cytotoxicity in drug resistant cancer cells against free DOX. In vivo antitumor effect also demonstrated the improved cancer inhibition effect. This work suggests that star-shaped polymers CD-g-TPGS are promising drug carriers to overcome MDR in cancer treatment.

Keywords: Cancer; Multidrug resistance; Nanomedicine; d-α-Tocopheryl polyethylene glycol succinate; β-Cyclodextrin.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Delivery Systems
  • Drug Resistance, Multiple / drug effects
  • Drug Resistance, Neoplasm / drug effects
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • MCF-7 Cells
  • Mice
  • Mice, Inbred Strains
  • Molecular Structure
  • Particle Size
  • Polyethylene Glycols / chemistry
  • Polymers / chemical synthesis
  • Polymers / chemistry*
  • Succinates / chemistry
  • Surface Properties
  • Tumor Cells, Cultured
  • Vitamin E / chemistry
  • beta-Cyclodextrins / chemistry

Substances

  • Antibiotics, Antineoplastic
  • Polymers
  • Succinates
  • beta-Cyclodextrins
  • Vitamin E
  • Polyethylene Glycols
  • Doxorubicin
  • tocophersolan