Polymeric drugs based on random copolymers with antimitotic activity

Biomacromolecules. 2010 Sep 13;11(9):2478-86. doi: 10.1021/bm100672c.

Abstract

Polymeric drugs based on random copolymers with antimitotic activity were obtained by free radical copolymerization of oleyl 2-acetamido-2-deoxy-α-d-glucopyranoside methacrylate (OAGMA) and 2-ethyl-(2-pyrrolidone) methacrylate (EPM) at low and high conversion and analyzed in terms of microstructure, physicochemical, and biological properties. Reactivity ratios of monomers were found to be r(OAGMA) = 1.34 and r(EPM) = 0.98, indicating the obtaining of statistical copolymers with random sequence distribution of the comonomeric units in the macromolecular chains. The glass transition temperature of the copolymers presents a negative deviation from the predicted values according to the Fox equation, suggesting a higher flexibility of the alternating diad. Copolymeric systems with OAGMA contents between 10-50 mol % presented thermosensitive behavior in a heating process showing cloud point temperatures (CPT) in the range 45-28 °C with increasing OAGMA content and hysteresis in one heating-and-cooling cycle. In vitro glycolipid release studies revealed the stability of the ester group in culture medium. The polymeric drugs with 30 and 50 mol % OAGMA presented antimitotic activity on a human glioblastoma line, but they were less toxic on normal human fibroblast cultures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimitotic Agents / chemical synthesis
  • Antimitotic Agents / chemistry
  • Antimitotic Agents / pharmacology*
  • Biocompatible Materials / chemical synthesis
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology*
  • Brain Neoplasms / drug therapy
  • Cells, Cultured
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Glioblastoma / drug therapy
  • Glycosides / chemistry
  • Glycosides / metabolism
  • Humans
  • Magnetic Resonance Spectroscopy
  • Methacrylates / chemistry*
  • Mitosis / drug effects*
  • Polymers / chemical synthesis
  • Polymers / chemistry
  • Polymers / pharmacology*

Substances

  • Antimitotic Agents
  • Biocompatible Materials
  • Glycosides
  • Methacrylates
  • Polymers