Optimization of perfluoro nano-scale emulsions: The importance of particle size for enhanced oxygen transfer in biomedical applications

Nano-scale emulsification has long been utilized by the food and cosmetics industry to maximize material delivery through increased surface area to volume ratios. More recently, these methods have been employed in the area of biomedical research to enhance and control the delivery of desired agents, as in perfluorocarbon emulsions for oxygen delivery. In this work, we evaluate critical factors for the optimization of PFC emulsions for use in cell-based applications. Cytotoxicity screening revealed minimal cytotoxicity of components, with the exception of one perfluorocarbon utilized for emulsion manufacture, perfluorooctylbromide (PFOB), and specific w% limitations of PEG-based surfactants utilized. We optimized the manufacture of stable nano-scale emulsions via evaluation of: component materials, emulsification time and pressure, and resulting particle size and temporal stability. The initial emulsion size was greatly dependent upon the emulsion surfactant tested, with pluronics providing the smallest size. Temporal stability of the nano-scale emulsions was directly related to the perfluorocarbon utilized, with perfluorotributylamine, FC-43, providing a highly stable emulsion, while perfluorodecalin, PFD, coalesced over time. The oxygen mass transfer, or diffusive permeability, of the resulting emulsions was also characterized. Our studies found particle size to be the critical factor affecting oxygen mass transfer, as increased micelle size resulted in reduced oxygen diffusion. Overall, this work demonstrates the importance of accurate characterization of emulsification parameters in order to generate stable, reproducible emulsions with the desired bio-delivery properties.