title: Exceptionally stable fluorous emulsions for the intravenous delivery of volatile general anesthetics.
abstract: BACKGROUND
  IV delivery of volatile fluorinated anesthetics has a number of potential advantages when compared with the current inhalation method of administration. We reported previously that the IV delivery of sevoflurane can be achieved through an emulsion composed of a linear fluorinated diblock copolymer, a stabilizer, and the anesthetic. However, this original emulsion was subject to particle size growth that would limit its potential clinical utility. We hypothesized that the use of bulkier fluorous groups and smaller polyethylene glycol moieties in the polymer design would result in improved emulsion stability while maintaining anesthetic functionality.
  
  
  METHODS
  The authors prepared emulsions incorporating sevoflurane, perfluorooctyl bromide as a stabilizing agent, and combinations of linear fluorinated diblock copolymer and a novel dibranched fluorinated diblock copolymer. Emulsion stability was assessed using dynamic light scattering. The ability of the emulsions to induce anesthesia was tested in vivo by administering them intravenously to 15 male Sprague-Dawley rats and measuring loss of the forepaw righting reflex.
  
  
  RESULTS
  20% (volume/volume) sevoflurane emulsions incorporating mixtures of dibranched and linear diblock copolymers had improved stability, with those containing an excess of the dibranched polymers displaying stability of particle size for more than 1 yr. The ED50s for loss of forepaw-righting reflex were all similar, and ranged between 0.55- 0.60 ml/kg body weight.
  
  
  CONCLUSIONS
  Hemifluorinated dibranched polymers can be used to generate exceptionally stable sevoflurane nanoemulsions, as required of formulations intended for clinical use. IV delivery of the emulsion in rats resulted in induction of anesthesia with rapid onset and smooth and rapid recovery.
authors.affiliation: School of Pharmacy, Department of Anesthesiology,University of Wisconsin, Madison, Wisconsin 53705, USA.
authors.forename: Jun-Pil
authors.initials: JP
authors.lastname: Jee
authors.forename: Maria C
authors.initials: MC
authors.lastname: Parlato
authors.forename: Mark G
authors.initials: MG
authors.lastname: Perkins
authors.forename: Sandro
authors.initials: S
authors.lastname: Mecozzi
authors.forename: Robert A
authors.initials: RA
authors.lastname: Pearce
mesh_terms: D018681:Anesthetics, General / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D004655:Emulsions; D005459:Fluorides / Q000008:administration & dosage / Q000737:chemistry; D007262:Infusions, Intravenous; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D014835:Volatilization
chemical_list: D018681:Anesthetics, General; D004655:Emulsions; D008738:Methyl Ethers; D000077149:Sevoflurane; D005459:Fluorides