Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion

Michael R. Fettiplace, Kinga Lis, Richard Ripper, Katarzyna Kowal, Adrian Pichurko, Dominic Vitello, Israel Rubinstein, David Schwartz, Belinda S. Akpa*, Guy Weinberg

*Corresponding author for this work

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Triglyceride micro-emulsions such as Intralipid® have been used to reverse cardiac toxicity induced by a number of drugs but reservations about their broad-spectrum applicability remain because of the poorly understood mechanism of action. Herein we report an integrated mechanism of reversal of bupivacaine toxicity that includes both transient drug scavenging and a cardiotonic effect that couple to accelerate movement of the toxin away from sites of toxicity. We thus propose a multi-modal therapeutic paradigm for colloidal bio-detoxification whereby a micro-emulsion both improves cardiac output and rapidly ferries the drug away from organs subject to toxicity. In vivo and in silico models of toxicity were combined to test the contribution of individual mechanisms and reveal the multi-modal role played by the cardiotonic and scavenging actions of the triglyceride suspension. These results suggest a method to predict which drug toxicities are most amenable to treatment and inform the design of next-generation therapeutics for drug overdose.

Original languageEnglish (US)
Pages (from-to)62-70
Number of pages9
JournalJournal of Controlled Release
Volume198
DOIs
StatePublished - Jan 28 2015

Keywords

  • Antidote
  • Biodetoxification
  • Bupivacaine
  • Lipid emulsion
  • Local anesthetic
  • Triglyceride

ASJC Scopus subject areas

  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion'. Together they form a unique fingerprint.

  • Cite this

    Fettiplace, M. R., Lis, K., Ripper, R., Kowal, K., Pichurko, A., Vitello, D., Rubinstein, I., Schwartz, D., Akpa, B. S., & Weinberg, G. (2015). Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion. Journal of Controlled Release, 198, 62-70. https://doi.org/10.1016/j.jconrel.2014.11.018