Influence of emulsification conditions on the preparation of nanoparticle-stabilized antibubbles: High-shear homogenization versus premix membrane emulsification

Antibubbles, characterized by a water-in-air-in-water structure, are a novel dispersion system stabilized by the adsorption of nanoparticles (e.g., silica nanoparticles) at the air-liquid interface and produced via the emulsification-sublimation-rehydration technique. Traditionally, shear-based homogenization has been the standard method for creating Pickering double emulsions, which are then converted into particle-stabilized antibubbles. However, efficient drug delivery using antibubbles requires a small size, narrow size distribution, and high active loading, which are challenges typically faced with shear-based methods. This study introduces the formation of antibubbles using premix membrane emulsification (PME), a gentle technique ideal for heat- and shear-sensitive materials. We conducted a thorough investigation, producing primary and double emulsions with both high-shear homogenization (HSH) and PME through Shirasu porous glass (SPG) membranes. Antibubble size distribution and entrapment efficiency (using a model drug) were analyzed in relation to the process parameters of the emulsification techniques. We found that PME, particularly when using a 30 μm SPG membrane in the secondary emulsification stage, yielded antibubbles with smaller sizes (down to 5 μm in diameter) and significantly higher encapsulation efficiency (up to 80 %) compared to HSH. These findings highlight PME's potential as a superior method for producing nanoparticle-stabilized antibubbles for drug delivery applications.