Preparation of acid-responsive antibubbles from CaCO₃-based Pickering emulsions

Hydrophobized fumed silica particles were previously reported for producing antibubbles that are quite stable in neutral as well as in acidic media. To produce acid-responsive antibubbles (e.g., for gastric drug delivery), the silica nanoparticles must be replaced by suitable particles, e.g., calcium carbonate (CaCO₃), which can degrade at low pH to release the encapsulated drug.

Two variants of CaCO₃-stabilized antibubbles were prepared (by using CaCO₃ particles pre-coated with stearic acid, or by using native CaCO₃ particles in combination with sodium stearoyl lactylate) and drug release was compared with classic antibubbles produced with hydrophobized fumed silica particles.

CaCO₃ particles (pre-coated with stearic acid) can be used to produce stable antibubbles, which provided an entrapment efficiency of a model drug (methylene blue, MB) of around 85%. A burst release of MB (∼60%) from the antibubbles was observed at pH 2 (i.e., the pH of the stomach), which was further increased to 80% during the next 30 min. On the contrary, at neutral pH, about 70% of the drug remained encapsulated for at least 2 h. We further demonstrated that the acidic conditions led to the desorption of CaCO₃ particles from the air-liquid interface resulting in the destabilization of the antibubbles and the release of drug-containing cores.