Document Detail


Exceptionally stable fluorous emulsions for the intravenous delivery of volatile general anesthetics.
MedLine Citation:
PMID:  22354241     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Jun-Pil Jee; Maria C Parlato; Mark G Perkins; Sandro Mecozzi; Robert A Pearce
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesiology     Volume:  116     ISSN:  1528-1175     ISO Abbreviation:  Anesthesiology     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-02-22     Completed Date:  2012-04-10     Revised Date:  2013-05-20    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  580-5     Citation Subset:  AIM; IM    
Affiliation:
School of Pharmacy, Department of Anesthesiology,University of Wisconsin, Madison, Wisconsin 53705, USA.
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MeSH Terms
Descriptor/Qualifier:
Anesthetics, General / administration & dosage*,  chemistry
Animals
Dose-Response Relationship, Drug
Drug Stability
Emulsions
Fluorides / administration & dosage,  chemistry
Infusions, Intravenous
Male
Methyl Ethers / administration & dosage*,  chemistry
Rats
Rats, Sprague-Dawley
Volatilization
Grant Support
ID/Acronym/Agency:
GM079375/GM/NIGMS NIH HHS; R01 GM079375-04/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Anesthetics, General; 0/Emulsions; 0/Fluorides; 0/Methyl Ethers; 28523-86-6/sevoflurane
Comments/Corrections
Comment In:
Anesthesiology. 2012 Mar;116(3):504-6   [PMID:  22261796 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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