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

Abstract

HYPOTHESIS: 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 (CaCO 3), which can degrade at low pH to release the encapsulated drug. EXPERIMENTS: Two variants of CaCO 3-stabilized antibubbles were prepared (by using CaCO 3 particles pre-coated with stearic acid, or by using native CaCO 3 particles in combination with sodium stearoyl lactylate) and drug release was compared with classic antibubbles produced with hydrophobized fumed silica particles. FINDINGS: CaCO 3 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 CaCO 3 particles from the air-liquid interface resulting in the destabilization of the antibubbles and the release of drug-containing cores.