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

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.