| Exceptionally stable fluorous emulsions for the intravenous delivery of volatile general anesthetics. | |
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MedLine Citation:
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PMID: 22354241 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Jun-Pil Jee; Maria C Parlato; Mark G Perkins; Sandro Mecozzi; Robert A Pearce |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Anesthesiology Volume: 116 ISSN: 1528-1175 ISO Abbreviation: Anesthesiology Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-02-22 Completed Date: 2012-04-10 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 1300217 Medline TA: Anesthesiology Country: United States |
Other Details:
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Languages: eng Pagination: 580-5 Citation Subset: AIM; IM |
Affiliation:
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School of Pharmacy, Department of Anesthesiology,University of Wisconsin, Madison, Wisconsin 53705, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anesthetics, General
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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:
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GM079375/GM/NIGMS NIH HHS; R01 GM079375-04/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anesthetics, General; 0/Emulsions; 0/Fluorides; 0/Methyl Ethers; 28523-86-6/sevoflurane |
| Comments/Corrections | |
Comment In:
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Anesthesiology. 2012 Mar;116(3):504-6
[PMID:
22261796
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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