Biomedical perfluorohexane-loaded nanocapsules prepared by low-energy emulsification and selective solvent diffusion

Perfluorohexane-loaded nanocapsules are interesting materials for many biomedical applications such as oxygen delivery systems or contrast agents. However, their formulation into stable colloidal systems is challenging because of their hydro- and lipophobicity, high density and high vapour pressure. In this study, perfluorohexane-loaded polymeric nanocapsules are prepared for the first time by low-energy emulsification and selective solvent diffusion. The colloidal stability of the perfluorohexane nano-emulsion templates has been improved by the incorporation of an apolar low-density oil (isopropyl myristate) in the dispersed phase, thus addressing droplet coarsening and migration phenomena. The perfluorohexane-loaded nanocapsules prepared from the nano-emulsions show sizes smaller than the corresponding emulsion templates (below 150 nm by dynamic light scattering) and exhibit good stability under storage conditions. Hyperspectral enhanced dark field microscopy revealed a layered core/shell structure and allowed also to confirm the encapsulation of perfluorohexane which was quantified by elemental microanalysis. Although isopropyl myristate has an unfavourable biocompatibility profile, cell viability is enhanced when perfluorohexane is present in the nanocapsules, which is attributed to its high oxygen transport capacity.