Controlling Complex Nanoemulsion Morphology Using Asymmetric Cosurfactants for the Preparation of Polymer Nanocapsules

Abstract

Complex nanoemulsions, comprising multiphase nanoscale droplets, hold considerable potential advantages as vehicles for encapsulation and delivery as well as templates for nanoparticle synthesis. Although methods exist to controllably produce complex emulsions on the microscale, very few methods exist to produce them on the nanoscale. Here, we examine a recently developed method involving a combination of high-energy emulsification with conventional cosurfactants to produce oil-water-oil (O/W/O) complex nanoemulsions. Specifically, we study in detail how the composition of conventional ethoxylated cosurfactants Span80 and Tween20 influences the morphology and structure of the resulting complex nanoemulsions in the water-cyclohexane system. Using a combination of small-angle neutron scattering and cryo-electron microscopy, we find that the cosurfactant composition controls the generation of complex droplet morphologies including core-shell and multicore-shell O/W/O nanodroplets, resulting in an effective state diagram for the selection of nanoemulsion morphology. Additionally, the cosurfactant composition can be used to control the thickness of the water shell contained within the complex nanodroplets. We hypothesize that this degree of control, despite the highly nonequilibrium nature of the nanoemulsions, is ultimately determined by a competition between the opposing spontaneous curvature of the two cosurfactants, which strongly influences the interfacial curvature of the nanodroplets as a result of their ultralow interfacial tension. This is supported by a correlation between cosurfactant compositions that produces complex nanoemulsions and those that produce homogeneous mixed micelles in equilibrium surfactant-cyclohexane solutions. Ultimately, we show that the formation of complex O/W/O nanoemulsions is weakly perturbed upon the addition of hydrophilic polymer precursors, facilitating their use as templates for the formation of polymer nanocapsules.

Cross-talk between emulsion drops: how are hydrophilic reagents transported across oil phases?

“…If these drops are formed at the liquid--liquid interface, this interface must deform. Surfactants with small inverse packing parameters increase the local curvature of liquid--liquid interfaces, 64,65 thereby likely facilitating the formation of small drops in the presence of convective flows. 62,63 Indeed, our results suggest that the formation of these drops, and hence the transport of reagents across the oil shell, increases with decreasing inverse packing parameter of the surfactant, as indicated in Figure 3c.…”

Toward the Formulation of Stable Micro and Nano Double Emulsions through a Silica Coating on Internal Water Droplets

“…On the contrary, in the two-step processes (which we followed), the internal water may be different from the external water, which makes them more suited for optimizing the encapsulation efficiency. [13][14][15] The primary w 1 /O emulsion must be of very small size, preferably a nano-emulsion stabilized by a low HLB surfactant. Reverse emulsion is generally obtained by a high-energy method, using a high-pressure homogenizer or ultrasounds.…”

“…For example, such a co-encapsulation of drugs is critical for optimizing targeted therapies by the simultaneous co-delivery of anticancer species with another complementary cytotoxic molecule, anti-inflammatory agent or adjuvant. Double emulsion formulations at the nanoscale were already reported, [12][13][14][15]17,18 but always by turning one of the liquid phase, i.e. internal water or oil, into a polymerized matrix.…”

A Review on Polymer and Lipid-Based Nanocarriers and Its Application to Nano-Pharmaceutical and Food-Based Systems

“…High and low energy methods are used to prepare nanoemulsions, such as high-pressure homogenization, ultrasonication, phase inversion temperature and emulsion inversion point, bubble bursting method ( 32 ). Based on the components, Nanoemulsions can be categorized in three types, that is oil in water (O/W) type, water in oil (W/O) type, and bi-continuous/multiple emulsion where micro domains of oil and water phases are inter-dispersed (W/O/W and O/W/O) ( 33 – 36 ). Additionally, based on surface charge over the nano-droplets, nanoemulsions are categorized as neutral, anionic and cationic nanoemulsions ( 35 ).…”