Emulsions and microemulsions with a fluorocarbon phase

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Abstract

A phase III clinical study of a perfluorooctyl bromide emulsion demonstrated reduction and avoidance of donor blood transfusion in surgery. Novel fluorocarbon-in-water emulsions are being investigated, including emulsions highly stabilized by fluorocarbon–hydrocarbon diblocks and targeted emulsions for molecular imaging, diagnosis and drug delivery. Reverse water-in-fluorocarbon emulsions and microemulsions that have potential for pulmonary drug delivery are also being studied. Microemulsions with highly fluorinated components are being actively investigated, with applications in polymerization technology and as research tools.

Introduction

Emulsions with a fluorocarbon (or perfluorocarbon, PFC; perfluoroalkyl=F-alkyl; for the extended use of the F- and, by analogy, for the H-symbols, see [1]) phase are being investigated, essentially for their potential biomedical applications. Three main lines of research are being actively pursued: emulsions for in vivo oxygen delivery (blood substitutes); targeted emulsions for diagnosis and therapy; and water-in-PFC reverse emulsions for pulmonary drug delivery. Microemulsions with PFC phases or fluorosurfactants, including water-in-supercritical CO2 microemulsions, are being used in polymerization technology and provide valuable research tools.

Section snippets

Fluorocarbon-in-water emulsions—injectable oxygen carriers

The reasons for, basic concepts, industrial development, ‘physiology’ and clinical investigation of PFC emulsions destined to serve as in vivo oxygen carriers have recently been reviewed and discussed in some length [2]••[3]. Basic properties of PFCs can be found in Ref. [4], details on emulsion engineering in Ref. [5], an update on clinical trial status in Ref. [6]•• and a report on PFC blood substitute research in Russia in Ref. [7]; a review of the biomedical applications of fluorinated

Targeted fluorocarbon emulsions

Targeted PFC emulsions are being investigated for the purpose of molecular imaging, i.e. detection of molecular markers, such as proteins and other cell-surface receptors, characteristic of a given pathology; such emulsions have also potential for site-directed drug delivery [41]••. Important potential target pathologies include inflammation, atherosclerosis, tumor-related angiogenesis and thrombi. Detection and differentiation from normal tissue involves binding ligands specific for epitopes

Reverse water-in-fluorocarbon emulsions

Producing stable water-in-PFC emulsions was not a trivial challenge, since PFCs are extremely hydrophobic. Such emulsions were nevertheless obtained using strongly fluorophilic, weakly hydrophilic amphiphiles, namely F-alkyl dimorpholinophosphates, CnF2n+1CmH2mOP(O)[N(CH2CH2)2O]2 [51]. A range of new compositions has now been reported, including macro-, mini- and microemulsions [52]•. These emulsions have potential for use as pulmonary drug delivery systems [53]. Investigation of mixed

Microemulsions with highly fluorinated components

F-microemulsions represent approximately 10% of the literature on microemulsions and share numerous features, constraints and perspectives with standard non-fluorinated microemulsions [58]. F-microemulsions are defined as thermodynamically stable isotropic liquids containing domains of tens of nanometers, stabilized by an interfacial amphiphilic film. At least two mutually insoluble liquids and a surfactant are involved in the spontaneous formation of either droplets or bicontinuous

Summary and prospects

PFC-in-water emulsions have been demonstrated to dissolve, transport and deliver O2 in surgery. F-octyl bromide appears to be the best candidate PFC for this purpose and Oxygent™ is a well-designed, stable emulsion. Although extensive investigation found no evidence of any adverse effects of the emulsion, the suspension of a cardiopulmonary bypass trial with Oxygent™, most likely because of an inadequate protocol, is slowing down the development of injectable PFC-based O2 carriers. Protocol

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