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Isoflurane-loaded nanoemulsion prepared by high-pressure homogenization: investigation of stability and dose reduction in general anesthesia.
MedLine Citation:
PMID:  22888757     Owner:  NLM     Status:  In-Process    
Isoflurane is a halogenated ether which is used for general anesthesia. To stabilize a new formulation in order to evaluate the potential to reduce the dose required for general anesthesia, an isoflurane-loaded nanoemulsion was proposed. A high-pressure homogenization technique was used to develop drug-loaded nanoemulsions which presented droplet size of 150 +/- 0.78 nm with a narrow size distribution and low polydispersity index (0.08 +/- 0.01). The zeta potential was -18 +/- 2.4 mV and pH was 6.03 +/- 0.04. Rheological analysis showed Newtonian behavior for the formulations, whose physical stability was confirmed by multiple light scattering. It was verified that isoflurane volatilization did not occur in these formulations. The preclinical evaluation, carried out via the end-tidal isoflurane concentration, showed that the dose required for anesthetic maintenance significantly decreased when the nanostructured formulation was administered compared to inhaled isoflurane. There was no significant difference (p < 0.05) between experimental groups (inhaled isoflurane and intravenous isoflurane-loaded nanoemulsion) in terms of the cardiac rate, oxygen hemoglobin saturation, and arterial blood pressure, as well as the biomarkers of renal, hepatic and skeletal muscle system functionalities. Slight tachypnea, edema, and erythema were observed after isoflurane-loaded or unloaded-nanoemulsion. The stability and significant dose reduction observed for drug-loaded nanoemulsion render this formulation a promising option for intravenous delivery of isoflurane.
Carolina L Krahn; Renata P Raffin; Guilherme S Santos; Luciana B Queiroga; Ruben L Cavalcanti; Priscila Serpa; Eliane Dallegrave; Paulo E Mayorga; Adriana R Pohlmann; Cláudio C Natalini; Silvia S Guterres; Renata P Limberger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of biomedical nanotechnology     Volume:  8     ISSN:  1550-7033     ISO Abbreviation:  J Biomed Nanotechnol     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-08-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101230869     Medline TA:  J Biomed Nanotechnol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  849-58     Citation Subset:  IM    
Programa de Pós-Graduação em Ciências Farmacéuticas, Faculdade de Farmàcia, Universidade Federal do Rio Grande do Sul, Porto Alegre, 90040-060, Brazil.
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