Intravenous administration of halogenated inhaled anesthetics—research tool or real application?

Raphael, Jacob; Lynch, Carl

doi:10.1007/s12630-008-9026-1

Cited by 4 publications

(4 citation statements)

References 16 publications

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“…IV delivery of fluorinated ethers also offers a host of other advantages. 4,5 Recent reports have shown that protection against ischemia and reperfusion injury can be achieved with concentrations of anesthetic insufficient to cause hypnotic and anesthetic effects. 28 The IV delivery of small amounts of concentrated emulsified sevoflurane would be well suited to such applications.…”

Section: Discussionmentioning

confidence: 99%

Exceptionally Stable Fluorous Emulsions for the Intravenous Delivery of Volatile General Anesthetics

Jee¹,

Parlato²,

Perkins³

et al. 2012

Anesthesiology

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Background Intravenous delivery of volatile fluorinated anesthetics has a number of potential advantages when compared to 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 poly(ethylene 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 fifteen 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 over one year. The ED50s for loss of forepaw righting reflex were all similar, and ranged between 0.55 and 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. Intravenous delivery of the emulsion in rats resulted in induction of anesthesia with rapid onset and smooth and rapid recovery.

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Section: Discussionmentioning

confidence: 99%

Exceptionally Stable Fluorous Emulsions for the Intravenous Delivery of Volatile General Anesthetics

Jee¹,

Parlato²,

Perkins³

et al. 2012

Anesthesiology

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“…1 H NMR (CDCl 3 ): δ 1.43À1.49 (4H, m), 1.57À1.66 (8H, m), 2.03À2.12 (4H, m), 3.82 (s, 3H), 3.38À3.57 (9H, m), 3.58À3.83 (m, PEG). 19 F NMR (CDCl 3 ): δ À81.7 (3F), À117.3 (2F), À124.7 (2F), À124.7 (4F), À125.6 (2F), À126.4 (2F), À129.4 (2F).…”

Section: ' Experimental Sectionmentioning

confidence: 99%

“…Therefore, the potential clinical applications of intravenous emulsified fluorinated anesthetics may well extend beyond the operating room. 19 Sevoflurane, a moderately water soluble highly fluorinated ether, used for induction and maintenance of general anesthesia, is the preferred agent in clinical anesthesia, due to less irritation to mucous membranes in comparison to that for other fluorous ethers with anesthetic properties such as isoflurane and desflurane. 20,21 The affinity of fluorinated anesthetics for fluorophilic molecules prompted the investigation of the emulsification of sevoflurane using the semifluorinated surfactant M 5 F 13 (Figure 1) with the fluorinated and FDA-approved additive perfluorooctyl bromide to slow ripening.…”

Section: ' Introductionmentioning

confidence: 99%

“…Additionally, the intravenous administration of fluorinated ethers has promising implications regarding end-organ protection against ischemia and reperfusion injury. , This preconditioning is found to be a separate pharmacologic response from the drug effects that result in general anesthesia. Therefore, the potential clinical applications of intravenous emulsified fluorinated anesthetics may well extend beyond the operating room . Sevoflurane, a moderately water soluble highly fluorinated ether, used for induction and maintenance of general anesthesia, is the preferred agent in clinical anesthesia, due to less irritation to mucous membranes in comparison to that for other fluorous ethers with anesthetic properties such as isoflurane and desflurane. , The affinity of fluorinated anesthetics for fluorophilic molecules prompted the investigation of the emulsification of sevoflurane using the semifluorinated surfactant M 5 F 13 (Figure ) with the fluorinated and FDA-approved additive perfluorooctyl bromide to slow ripening.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, Characterization, and Applications of Hemifluorinated Dibranched Amphiphiles

et al. 2011

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Here we describe the synthesis, the physicochemical and preliminary pharmaceutical assessment of a novel class of hemifluorinated dibranched derivatives (M1diHxFy). These novel compounds have the remarkable ability of completely stopping the Ostwald ripening commonly associated with nanoemulsions. The developed synthesis is modular and it allows easy incremental structural variations in the fluorophilic (fluorous chains)-, lipophilic (alkyl spacer head)- and hydrophilic (polar head) domains. Furthermore, the synthesis can be easily scaled-up and highly pure compounds can be readily obtained through silica gel and fluoro-silica gel column chromatography, without any need to use HPLC or other time-consuming techniques. Surface properties like micelle formation, critical aggregation concentration (CAC) and emulsion stability studies demonstrated the different behavior of dibranched hemifluorinated surfactant (M1diHxFy) with respect to that of single chain semifluorinated analogues (MzFy). Remarkably, the new polymer M1diH3F8 drastically slowed the ripening of nanoemulsions of the commonly used fluorinated anesthetic sevoflurane over a period of more than one year. During this time, the nanodroplet size did not increase to more than 400 nm. This result is very promising for inducing and maintaining general anesthesia through intravenous delivery of volatile anesthetics, eliminating the need for the use of large and costly vaporizers in the operating room.

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Stable perfluorocarbon emulsions for the delivery of halogenated ether anesthetics

Ashrafi

Tootoonchi

Bardsley³

et al. 2018

Colloids and Surfaces B: Biointerfaces

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Intravenous administration of halogenated inhaled anesthetics—research tool or real application?

Cited by 4 publications

References 16 publications

Exceptionally Stable Fluorous Emulsions for the Intravenous Delivery of Volatile General Anesthetics

Exceptionally Stable Fluorous Emulsions for the Intravenous Delivery of Volatile General Anesthetics

Synthesis, Characterization, and Applications of Hemifluorinated Dibranched Amphiphiles

Stable perfluorocarbon emulsions for the delivery of halogenated ether anesthetics

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