Methacrylic-based nanogels for the pH-sensitive delivery of 5-fluorouracil in the colon

Int J Nanomedicine. 2012;7:5769-79. doi: 10.2147/IJN.S31201. Epub 2012 Nov 15.

Abstract

Methacrylic-based copolymers in drug-delivery systems demonstrate a pH-sensitive drug-releasing behavior in the colon. In this study, copolymers of methacrylic acid and 2-ethyl hexyl acrylate were prepared using a microemulsion polymerization technique. The purified copolymer was characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and differential scanning calorimetry. 5-Fluorouracil (5-FU) was entrapped within methacrylic-based copolymers by a solvent evaporation method. The size of the nanogels formed was characterized by transmission electron microscopy and atomic force microscopy. In vitro drug-release studies using phosphate-buffered saline at different pH levels demonstrated the sustained release of 5-FU and its pH dependence. Cell proliferation assay of a human colon tumor colon cancer cell line (HCT-116) was performed and showed that the nanogels containing 5-FU exhibited considerable cytotoxicity in comparison with free 5-FU. Cell uptake of the nanogels was also monitored using confocal microscopy. Western blot analysis and flow cytometry studies confirmed that the nanogels could be successfully used as an efficient vector for pH-sensitive and controlled delivery of drugs specifically targeted to the colon.

Keywords: 5-FU; colon cancer; methacrylic polymer; nanogel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / chemical synthesis
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / chemical synthesis*
  • Fluorouracil / administration & dosage*
  • Fluorouracil / chemistry*
  • Gels / chemistry
  • Humans
  • Hydrogen-Ion Concentration
  • Methacrylates / chemistry*
  • Nanocapsules / administration & dosage
  • Nanocapsules / chemistry*
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • Delayed-Action Preparations
  • Gels
  • Methacrylates
  • Nanocapsules
  • methacrylic acid
  • Fluorouracil