作者
Michael R Fettiplace, Kinga Lis, Richard Ripper, Katarzyna Kowal, Adrian Pichurko, Dominic Vitello, Israel Rubinstein, David Schwartz, Belinda S Akpa, Guy Weinberg
发表日期
2015/1/28
期刊
Journal of Controlled Release
卷号
198
页码范围
62-70
出版商
Elsevier
简介
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 …
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