Polymeric drugs based on bioactive glycosides for the treatment of brain tumours

Biomaterials. 2009 Mar;30(8):1613-26. doi: 10.1016/j.biomaterials.2008.12.006. Epub 2009 Jan 7.

Abstract

Polymeric drugs carrying glycolipids have been designed as target macromolecules for the treatment of brain tumours. A methacrylate derivative of oleyl 2-acetamido-2-deoxy-alpha-D-glucopyranoside (OAGMA) has been prepared and the corresponding glycopolymer obtained by free radical polymerisation. To modulate the hydrophobic character of the polymeric drug, the acrylic glycomonomer was copolymerised with vinyl pyrrolidone (VP). Reactivity ratios obtained by performing copolymerisation reactions inside the NMR apparatus were r(OAGMA)=5.94 and r(VP)=0.01, indicating the much higher reactivity of the glycomonomer. The hydrolytical release of oleyl 2-acetamido-2-deoxy-alpha-D-glucopyranoside (OAG) from the copolymeric drugs was produced in vitro by the ester enzymatic hydrolysis using enzyme/buffered solutions. The cytotoxicity of OAG and OAGMA tested against a human glioblastoma line and normal fibroblasts revealed a concentration dependent selectivity towards tumour cells versus fibroblasts. The antimitotic activity of the copolymeric drugs was also confirmed. The addition of the eluates of the copolymeric systems collected at 1 and 2 days produced a significant decrease in cellular viability of the glioblastoma cells without affecting that of normal fibroblasts. On the contrary, fibroblasts were able to adhere and proliferate onto the copolymeric systems showing normal morphology and revealing a good biocompatibility of the copolymeric drugs against healthy cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology
  • Glycosides / chemical synthesis
  • Glycosides / chemistry
  • Glycosides / therapeutic use*
  • Humans
  • Hydrogen-Ion Concentration / drug effects
  • L-Lactate Dehydrogenase / metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Mitosis / drug effects
  • Polyethylene Terephthalates / pharmacology
  • Polymers / chemical synthesis
  • Polymers / chemistry
  • Polymers / therapeutic use*
  • Pyrrolidines / chemistry
  • Temperature

Substances

  • Antineoplastic Agents
  • Glycosides
  • Polyethylene Terephthalates
  • Polymers
  • Pyrrolidines
  • Thermanox
  • L-Lactate Dehydrogenase