Stable perfluorocarbon emulsions for the delivery of halogenated ether anesthetics

Behrouz Ashrafi, Mohammad Hossein Tootoonchi, Ryan Bardsley, Ruth Molano, Phillip Ruiz, Ernesto Pretto, Christopher Fraker

Research output: Contribution to journalArticle

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)797-805
Number of pages9
JournalColloids and Surfaces B: Biointerfaces
Volume172
DOIs
StatePublished - Dec 1 2018

Fingerprint

anesthetics
Fluorocarbons
Anesthetics
Emulsions
Ether
emulsions
Ethers
ethers
delivery
anesthesia
reflexes
Isoflurane
Particle Size
blood
safety
induction
Blood
Particle size
chemistry
Righting Reflex

Keywords

  • Anesthesia
  • Emulsions
  • Halogenated ethers
  • Intravenous
  • Perfluorocarbon

ASJC Scopus subject areas

  • Biotechnology
  • Surfaces and Interfaces
  • Physical and Theoretical Chemistry
  • Colloid and Surface Chemistry

Cite this

Stable perfluorocarbon emulsions for the delivery of halogenated ether anesthetics. / Ashrafi, Behrouz; Tootoonchi, Mohammad Hossein; Bardsley, Ryan; Molano, Ruth; Ruiz, Phillip; Pretto, Ernesto; Fraker, Christopher.

In: Colloids and Surfaces B: Biointerfaces, Vol. 172, 01.12.2018, p. 797-805.

Research output: Contribution to journalArticle

Ashrafi, Behrouz ; Tootoonchi, Mohammad Hossein ; Bardsley, Ryan ; Molano, Ruth ; Ruiz, Phillip ; Pretto, Ernesto ; Fraker, Christopher. / Stable perfluorocarbon emulsions for the delivery of halogenated ether anesthetics. In: Colloids and Surfaces B: Biointerfaces. 2018 ; Vol. 172. pp. 797-805.
@article{b50b0adebf5c473e8964ef2d22d2c1c9,
title = "Stable perfluorocarbon emulsions for the delivery of halogenated ether anesthetics",
abstract = "Background: 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. Methods: 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. Results: 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. Conclusions: 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.",
keywords = "Anesthesia, Emulsions, Halogenated ethers, Intravenous, Perfluorocarbon",
author = "Behrouz Ashrafi and Tootoonchi, {Mohammad Hossein} and Ryan Bardsley and Ruth Molano and Phillip Ruiz and Ernesto Pretto and Christopher Fraker",
year = "2018",
month = "12",
day = "1",
doi = "10.1016/j.colsurfb.2018.09.024",
language = "English (US)",
volume = "172",
pages = "797--805",
journal = "Colloids and Surfaces B: Biointerfaces",
issn = "0927-7765",
publisher = "Elsevier",

}

TY - JOUR

T1 - Stable perfluorocarbon emulsions for the delivery of halogenated ether anesthetics

AU - Ashrafi, Behrouz

AU - Tootoonchi, Mohammad Hossein

AU - Bardsley, Ryan

AU - Molano, Ruth

AU - Ruiz, Phillip

AU - Pretto, Ernesto

AU - Fraker, Christopher

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Background: 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. Methods: 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. Results: 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. Conclusions: 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.

AB - Background: 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. Methods: 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. Results: 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. Conclusions: 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.

KW - Anesthesia

KW - Emulsions

KW - Halogenated ethers

KW - Intravenous

KW - Perfluorocarbon

UR - http://www.scopus.com/inward/record.url?scp=85054926833&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054926833&partnerID=8YFLogxK

U2 - 10.1016/j.colsurfb.2018.09.024

DO - 10.1016/j.colsurfb.2018.09.024

M3 - Article

C2 - 30342412

AN - SCOPUS:85054926833

VL - 172

SP - 797

EP - 805

JO - Colloids and Surfaces B: Biointerfaces

JF - Colloids and Surfaces B: Biointerfaces

SN - 0927-7765

ER -