Parenteral emulsions and liposomes to treat drug overdose

Drug overdoses from both pharmaceutical and recreational drugs are a major public health concern. Although some overdoses may be treated with specific antidotes, the most common treatment involves providing supportive care to allow the body to metabolize and excrete the toxicant. In many cases, supportive care is limiting, ineffective, and expensive. There is a clear medical need to improve the effectiveness of detoxification, in particular by developing more specific therapies or antidotes for these overdoses. Intravenous lipid emulsions (ILEs) have been investigated as a potential treatment for overdoses of local anesthetics and other hydrophobic drugs. While ILE therapy has been successful in several cases, its use beyond local anesthetic systemic toxicity is controversial and its mechanism of detoxification remains a subject of debate. ILEs were not originally developed to treat overdose, but clarifying the mechanisms of detoxification observed with ILE may allow us to design more effective future treatments. Liposomes are highly biocompatible and versatile formulations, thus it was a natural step to explore their use for drug overdose therapy as well. Several researchers have designed liposomes using a variety of approaches including surface charge, pH gradients, and inclusion of enzymes in the liposome core to optimize the formulations for detoxification of a specific drug or toxicant. The in vitro results for drug sequestration by liposomes are very promising and animal trials have in some cases shown comparable performance to ILE at reduced lipid dosing. This narrative review summarizes the current status and advances in the use of emulsions and liposomes for detoxification and also suggests several areas in which studies are needed for developing future therapies. (C) 2015 Elsevier B.V. All rights reserved.