Etomidate-loaded micelles for short-acting general anesthesia: Preparation, characterizations, and in vivo studies

Abstract

Etomidate is one of the most commonly used intravenous (i.v.) general anesthetics with rapid onset, minimal impact on breathing and excellent hemodynamic stability. But its application is usually coupled with several disadvantages including inadequate water-solubility for injection and adrenal toxicity in particular. Selective delivery of etomidate to brain via some water-soluble nanocarriers provides a potential way to settle these problems. In this study, etomidate-loaded poloxamer micelles (Eto-SOPM) were prepared using a thin-film hydration method. Soybean oil (SO) was used to enhance the encapsulation of etomidate, which resulted in acceptable drug concentration (2 mg/mL) for injection. The drug release of Eto-SOPM was not significantly hindered by encapsulation or the addition of soybean oil, and was faster than that of the commercially available etomidate fat emulsion (P < 0.001). The in vivo study revealed that the drug potency of etomidate was not significantly affected by encapsulation, and that Eto-SOPM had notably shortened action period as compared with etomidate fat emulsion (P < 0.001). As rapid onset and short action period are two essential requirements of general anesthetics, these results suggested that Eto-SOPM represents a promising etomidate preparation for short-acting general anesthesia and warrants more study in the future.