Multi-inhibitor prodrug constructs for simultaneous delivery of anti-inflammatory agents to mustard-induced skin injury

Ann N Y Acad Sci. 2016 Aug;1378(1):174-179. doi: 10.1111/nyas.13177. Epub 2016 Aug 9.

Abstract

The molecular pathology of sulfur mustard injury is complex, with at least nine inflammation-related enzymes and receptors upregulated in the zone of the insult. A new approach wherein inhibitors of these targets have been linked by hydrolyzable bonds, either one to one or via separate preattachment to a carrier molecule, has been shown to significantly enhance the therapeutic response compared with the individual agents. This article reviews the published work of the authors in this drug development domain over the last 8 years.

Keywords: bifunctionals; chloroethylethylsulfide; inflammation; phorbol ester; skin; sulfur mustard; vesicants.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / metabolism
  • Chemical Warfare Agents / metabolism
  • Chemical Warfare Agents / toxicity*
  • Cholinesterase Inhibitors / administration & dosage
  • Cholinesterase Inhibitors / metabolism
  • Cyclooxygenase Inhibitors / administration & dosage
  • Cyclooxygenase Inhibitors / metabolism
  • Drug Delivery Systems / methods*
  • Drug Delivery Systems / trends
  • Drug Discovery / trends
  • Humans
  • Mustard Gas / metabolism
  • Mustard Gas / toxicity*
  • Prodrugs / administration & dosage*
  • Prodrugs / metabolism
  • Skin / drug effects*
  • Skin / injuries
  • Skin / metabolism

Substances

  • Anti-Inflammatory Agents
  • Chemical Warfare Agents
  • Cholinesterase Inhibitors
  • Cyclooxygenase Inhibitors
  • Prodrugs
  • Mustard Gas