Mixed micelle as nanocarrier for etomidate: Development, in vitro characterizations, and in vivo study on toxicity and anesthetic effects

Abstract

Etomidate is one of the first-line general anesthetic agents, with distinguished properties such as rapid onset, excellent cardiovascular stability, minimal impact on respiratory system, etc. However, the clinical application of etomidate preparation is often confined by the notable defects of both the drug and its current formulations. Previously, we reported a new etomidate formulation based on Pluronic F108 micelle which demonstrated improved anesthetic effects. Nevertheless, the micellar encapsulation of etomidate was limited using only one kind of Pluronic, which required organic solvents to modulate the hydrophobicity. Besides, the biocompatibility of this formulation was not yet clear. Herein, we reported that mixed nanomicelles consisting of different Pluronic could make full advantage of each loading material, which led to improved physicochemical properties for the delivery of etomidate. Moreover, in vivo studies demonstrated that, the etomidate-loaded mixed micelle (Eto-PFM) maintained the anesthetic effects and rapid onset property of etomidate, with a broad safe dose range. The potential mechanisms of the acute toxicity were also discussed. The results suggest that Eto-PFM is a promising etomidate preparation with the potential to further develop as an alternative to the current etomidate preparations.