Intravenous Delivery of Xenon Incorporated in Thermosensitive Nano-Emulsions for Anesthesia.

ABSTRACT

Xenon anesthesia has several advantages over conventional anesthetics, however, it has not been widely used in clinical sites, since the cost and minimum alveolar concentration were higher than conventional inhalational anesthetics. The purpose of this study was to develop an optimum vehicle for stable intravenous delivery of xenon with sufficient concentration. Thermosensitive lipid based nano-emulsions (TS-LE) were prepared by blending medium chain triglyceride, polyethylene glycol-15-hydroxystearate, D-α tocopherol polyethylene glycol succinate and Poloxamer 188. Three folds higher xenon was loaded in TS-LE when it was prepared under 5.5 atm of xenon pressure compared to that under 1 atm of xenon pressure at 22 °C (11.4±0.7 vs. 3.82±0.34 mg/ml). Poloxamer 188 conferred thermosensitive viscosity and outer rigid structure on TS-LE, and the properties led to the enhanced stability of xenon compared to usual lipid emulsion. Induction of anesthesia was investigated by monitoring loss of forepaw righting reflex (LORR) in rats. The ED50 for LORR was 131.9 mg/kg and the anesthesia was maintained for 65.3±7.1 sec at a dose of 179 mg/kg in rats. When it is considered that TS-LE stably loads enough concentration of xenon for the induction of therapeutically sufficient anesthesia, TS-LE may be regarded as a promising candidate for intravenous xenon delivery.