Biocompatible hyperbranched polyglycerol modified β-cyclodextrin derivatives for docetaxel delivery

Mater Sci Eng C Mater Biol Appl. 2017 Feb 1:71:965-972. doi: 10.1016/j.msec.2016.11.005. Epub 2016 Nov 4.

Abstract

The development of biocompatible vector for hydrophobic drug delivery remains a longstanding issue in cancer therapy. We design and synthesis a drug delivery system based on HPG modified β-CD (β-CD-HPG) by conjugating HPG branches onto β-CD core and its structure was confirmed by NMR, FTIR, GPC and solubility. In vitro biocompatibility tests showed that HPG modification significantly improved red blood cells morphology alteration and hemolysis cause by β-CD and β-CD-HPG displayed cell safety apparently in a wide range of 0.01-1mg/mL. An anti-cancer drug, docetaxel, was effectively encapsulated into β-CD-HPG which was confirmed by DSC analysis. This copolymer could form nanoparticles with small size (<200nm) and exhibited better DTX loading capacity and controlled release kinetics without initial burst release behavior compared with β-CD. Furthermore, antitumor assay in vitro show that β-CD-HPG/DTX effectively inhibited proliferation of human breast adenocarcinoma cells. Therefore, β-CD-HPG/DTX exhibit great potential for cancer chemotherapy.

Keywords: Biocompatibility; Cancer therapy; Drug carrier; Hyperbranched polyglycerol (HPG); β-Cyclodextrin (β-CD).

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacokinetics
  • Delayed-Action Preparations / pharmacology
  • Docetaxel
  • Drug Screening Assays, Antitumor
  • Erythrocytes / metabolism
  • Female
  • Glycerol* / chemistry
  • Glycerol* / pharmacokinetics
  • Glycerol* / pharmacology
  • Hemolysis / drug effects
  • Humans
  • Polymers* / chemistry
  • Polymers* / pharmacokinetics
  • Polymers* / pharmacology
  • Taxoids* / chemistry
  • Taxoids* / pharmacokinetics
  • Taxoids* / pharmacology
  • beta-Cyclodextrins* / chemistry
  • beta-Cyclodextrins* / pharmacokinetics
  • beta-Cyclodextrins* / pharmacology

Substances

  • Delayed-Action Preparations
  • Polymers
  • Taxoids
  • beta-Cyclodextrins
  • Docetaxel
  • polyglycerol
  • Glycerol