Isoflurane-loaded nanoemulsion prepared by high-pressure homogenization: investigation of stability and dose reduction in general anesthesia

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 d...

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Bibliographic Details
Published in:	Journal of biomedical nanotechnology Vol. 8; no. 5; p. 849
Main Authors:	Krahn, Carolina L, Raffin, Renata P, Santos, Guilherme S, Queiroga, Luciana B, Cavalcanti, Ruben L, Serpa, Priscila, Dallegrave, Eliane, Mayorga, Paulo E, Pohlmann, Adriana R, Natalini, Cláudio C, Guterres, Silvia S, Limberger, Renata P
Format:	Journal Article
Language:	English
Published:	United States 01-10-2012
Subjects:	Anesthetics, General - administration & dosage Anesthetics, General - chemistry Animals Blood Pressure - drug effects Dogs Dose-Response Relationship, Drug Drug Stability Emulsions - chemistry Female Heart Rate - drug effects Isoflurane - administration & dosage Isoflurane - chemistry Male Nanocapsules - administration & dosage Nanocapsules - chemistry Pressure Respiratory Rate - drug effects
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Summary:	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.
ISSN:	1550-7033
DOI:	10.1166/jbn.2012.1449