Reverse water-in-fluorocarbon emulsions as a drug delivery system:: an in vitro study

Liquid fluorocarbons with high gas-dissolving capacity, high fluidity, low surface tension, exceptional biological inertness, are in clinical trials for the treatment of acute respiratory failure by liquid ventilation. Fluorocarbons are able to reopen collapsed alveoli and facilitate the exchange of the respiratory gases. They also constitute a promising carrier for administration of drugs via the pulmonary route. Since pharmaceuticals are usually not soluble in fluorocarbons, we have designed and prepared reverse water-in-fluorocarbon emulsions. These emulsions are stabilized by perfluoroalkylated surfactants with a dimorpholinophosphate head group. They can be sterilized by heat or filtration through a 0.22 mu m membrane, and are stable (initial mean droplet diameter = 0.17 mu m, 0.26 mu m after 1 year at 25 degrees C). Various drugs, including antibiotics, vasodilators and anticancer agents, were incorporated in the aqueous phase of the emulsions. Preliminary biocompatibilty tests are encouraging. An in vitro study at 37 degrees C of the release of 5,6-carboxyfluorescein encapsulated in the internal phase of a reverse water-in-perfluorooctyl bromide emulsion was significantly slower than for a reverse water-in-octyl bromide emulsion (4% vs 37% of release after 6 h) or for a standard isopropyl myristate reverse emulsion stabilized by Span 80 (48% after 6 h). This is assigned to the extreme hydrophobic character of fluorocarbons which act as a physical barrier to diffusion of encapsulated hydrophilic compounds. (C) 1999 Elsevier Science B.V. All rights reserved.