Stable perfluorocarbon emulsions for the delivery of halogenated ether anesthetics
2018
Ashrafi, Behrouz | Tootoonchi, Mohammad Hossein | Bardsley, Ryan | Molano, Ruth Damaris | Ruiz, Phillip | Pretto, Ernesto A. | Fraker, Christopher A.
Research into injectable volatile anesthetics has been ongoing for approximately 40 years, with limited success, in an attempt to address the deficiencies of inhalational anesthesia. The purpose of this work was to formulate and optimize volatile anesthetic carrier emulsions based on our prior work in perfluorocarbon emulsions.Perfluorocarbons were screened for their volatilty and emulsion stability. Optimal anesthetic emulsions were manufactured by high pressure homogenization of a select, clinically relevant perfluorocarbon, isoflurane and a surfactant-containing aqueous phase. Longitudinal particle size, polydispersity and isoflurane content analysis was performed. Observational studies of in vivo efficacy and safety were performed in 225–300 g Lewis Rats (n = 34) with blood chemistry and post study tissue pathology analysis.Emulsion particle size and isolflurane content in select emulsions were stable at room temperature greater than 300 days. This stability was depedent on perfluorocarbon molecular weight and boiling point. in vivo, emulsions demonstrated a rapid onset and offset. Variability in onset metrics (loss of righting reflex, pain reflexes and time to recovery) was less than 40% amongst individual emulsion preparations (n = 9) utilized in induction trials. No adverse effects due to the intravenous administration of emulsions were observed in blood chemistry results or post-study pathological examination.These formulations showed stability, safety and efficacy. In addition to induction and general anesthesia, these emulsions could have utility in global health or in military applications where equipment and resources are limited.
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