Cerberus Nanoemulsions Produced by Multidroplet Flow-Induced Fusion

Abstract

Through extreme flow-induced fusion and rupturing of microscale droplets within a mixture of two or more oil-in-water emulsions, each having a different type of mutually immiscible oil, we create complex oil-in-water nanoemulsions composed of multicomponent compartmentalized nanodroplets. The extreme flow temporarily overcomes the repulsive barrier between oil droplets, arising from stabilizing surfactant molecules on the droplet interfaces, thereby causing multidroplet fusion as well as droplet fission down to the nanoscale. After the droplets leave the vicinity of extreme flow, they remain stable against subsequent coarsening and coalescence. Using this highly parallel, top-down, nonequilibrium synthetic approach, we create bulk quantities of engulfed-linear Cerberus oil-in-water nanoemulsions. Each Cerberus nanodroplet contains three different immiscible oils that form complex-shaped internal compartments, as revealed by cryogenic transmission electron microscopy (cryo-TEM). Within a given Cerberus nanodroplet, depending upon the interfacial tensions and relative volume fractions of the different oils, the internal oil-oil interfaces can be significantly deformed. Such multicomponent compartmentalized oil nanodroplets have the capacity of holding different types of oil-soluble cargo molecules, including fluorinated drug molecules, which have a wide variety of functional capacities and the potential for local synergistic effects. Their size range is small enough to permit a wide variety of pharmaceutical applications. As such, Cerberus nanoemulsions open up possibilities for simultaneously delivering several different types of oil-soluble drug molecules, each of which is readily soluble in at least one of the different types of immiscible oils, to the same cell or tissue.