A fast pH-switchable and self-healing supramolecular hydrogel carrier for guided, local catheter injection in the infarcted myocardium

Adv Healthc Mater. 2014 Jan;3(1):70-8. doi: 10.1002/adhm.201300076. Epub 2013 Jun 21.

Abstract

Minimally invasive intervention strategies after myocardial infarction use state-of-the-art catheter systems that are able to combine mapping of the infarcted area with precise, local injection of drugs. To this end, catheter delivery of drugs that are not immediately pumped out of the heart is still challenging, and requires a carrier matrix that in the solution state can be injected through a long catheter, and instantaneously gelates at the site of injection. To address this unmet need, a pH-switchable supramolecular hydrogel is developed. The supramolecular hydrogel is switched into a liquid at pH > 8.5, with a viscosity low enough to enable passage through a 1-m long catheter while rapidly forming a hydrogel in contact with tissue. The hydrogel has self-healing properties taking care of adjustment to the injection site. Growth factors are delivered from the hydrogel thereby clearly showing a reduction of infarct scar in a pig myocardial infarction model.

Keywords: catheter injection; drug delivery; myocardial infarction; pH-responsive hydrogel; supramolecular polymers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry*
  • Biocompatible Materials / metabolism
  • Cardiac Catheterization
  • Disease Models, Animal
  • Hepatocyte Growth Factor / chemistry
  • Hepatocyte Growth Factor / metabolism
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry*
  • Hydrogel, Polyethylene Glycol Dimethacrylate / metabolism
  • Hydrogen-Ion Concentration
  • Insulin-Like Growth Factor I / chemistry
  • Insulin-Like Growth Factor I / metabolism
  • Magnetic Resonance Imaging
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology*
  • Rheology
  • Swine
  • Viscosity

Substances

  • Biocompatible Materials
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Hepatocyte Growth Factor
  • Insulin-Like Growth Factor I