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

• Published in: Annals of the New York Academy of Sciences Vol. 1378; no. 1; pp. 174 - 179
• Main Authors: Lacey, Carl J., Wohlman, Irene, Guillon, Christophe, Saxena, Jaya, Fianu-Velgus, Cynthia, Aponte, Erik, Young, Sherri C., Heck, Diane E., Joseph, Laurie B., Laskin, Jeffrey D., Heindel, Ned D.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.08.2016; Wiley Subscription Services, Inc
• Subjects: Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - metabolism; bifunctionals; Chemical Warfare Agents - metabolism; Chemical Warfare Agents - toxicity; chloroethylethylsulfide; 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; inflammation; Mustard Gas - metabolism; Mustard Gas - toxicity; Pharmaceutical industry; phorbol ester; Prodrugs - administration & dosage; Prodrugs - metabolism; skin; Skin - drug effects; Skin - injuries; Skin - metabolism; sulfur mustard; vesicants; chloroethylethylsulfide; inflammation; phorbol ester; vesicants; skin; bifunctionals; sulfur mustard
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/nyas.13177

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.