The spontaneous emulsification is the phenomenon that droplet formation is achieved by contacting two immiscible solutions that are not in equilibrium. The author has reported the facile technique to prepare surface-modified polymeric nano/microparticles by an evaporation of organic solvents from o/w emulsion containing hydrophobic polymers and polymeric surfactant. In the research process, the author found that porous ultra-low-density particles were successfully obtained by using precisely controlled spontaneous emulsification. The review provides a brief review on recent efforts to develop the porous ultra-low-density biomaterials and their perspective.

Solid-in-Oil (S/O) nanodispersion is a novel emulsion formulation, in which hydrophilic macromolecular drugs are coated with hydrophobic surfactants and dispersed in an oil phase as nano-ordered particles. In this review, history and classification of S/O nanodispersions are described. The main topic of this review is a solid-in-oil-in-water (S/O/W) emulsion that is a multiple-emulsion using a S/O nanodispersion as an oil phase of oil-in-water emulsions. The first study using the S/O/W emulsion in a drug delivery system was focused on the carrier of oral delivery. Insulin was encapsulated in the S/O/W emulsion and released in a gastric condition. In the transdermal delivery, the S/O nanodispersion is known to be effective because skin has a hydrophobic barrier and the S/O/W emulsion is also applied to the transdermal drug delivery as a water-based formulation. In addition, the S/O/W emulsion was used as an encapsulation tool for gene or proteins. The double-coating carrier was effective for the intracellular delivery of gene or proteins. These results suggested that the S/O/W multiple emulsion would be a promising carrier for the drug delivery system of biomolecules.

Lipid vesicle is a molecular aggregate consisting of closed lipid bilayers formed in aqueous solution and it can be applied in various industries as carriers for drug delivery systems and encapsulation materials of other functional compounds. The authors recently developed a novel vesicle preparation method using water-in-oil-in-water type double emulsions. This method consisting of 3 steps: (1) primary emulsification for obtaining water-in-oil emulsion, (2) secondary emulsification for obtaining double emulsion, (3) removal of organic solvent from double emulsion for forming lipid vesicles. By this method, high encapsulation efficiency for hydrophilic compounds and size control of lipid vesicles could be achieved. The resulting vesicles showed good stability against autoclave treatment and powderization treatment by freeze-drying.

The authors developed a new technology for preparing various multiple emulsions using the membrane emulsification techniques named the direct emulsification method and the membrane permeation method. More than 800 patients bearing hepatocellular carcinoma have been treated attaining excellent results by transarterial injection chemotherapy with the W/O/W emulsion type drug, prepared by the direct emulsification method. On the other hand, our experimental trial including in vivo and in vitro fundamental researches with the S/O/W nano-emulsion drugs aimed at intravenous injection therapy for liver disease, prepared based on the membrane permeation method, showed interesting findings concerning a reticle-endotherial system evasion and the cellular targeting. We discuss that the potential of the multiple emulsion is high for medical supplies as things mentioned above.