Bile acid triggered release of daunorubicin from silica nanoparticle-stabilized antibubbles

We report on the preparation and release behavior of daunorubicin-loaded antibubbles targeted for intestinal drug release. The antibubbles were prepared from a Pickering-stabilized W₁/O/W₂ double emulsion, then freeze-dried and rehydrated to create the distinct structure of antibubbles, i.e., water-in-air-in-water (W₁/A/W₂). Daunorubicin was loaded into the inner aqueous phase, surrounded by two particle-stabilized interfaces separated by an air gap. Fumed silica nanoparticles with varying degrees of hydrophobicity were used to stabilize both interfaces. The antibubbles, when rehydrated, had a mean diameter of approximately 25 μm and a drug entrapment efficiency of >90%. The release profile showed a non-significant release of the drug in both acidic and neutral media. Notably, a burst release of the drug (around 60%) was observed when the antibubbles were exposed to bile salts in simulated intestinal conditions. Hence, the bile salts were a major driving force in dislocating the nanoparticles at the interfaces. We have supported our findings with quantitative drug-release measurements (measured spectrophotometrically) and microscopic observations of structural changes across different media. Furthermore, protection of the encapsulated daunorubicin from degradation was investigated when the antibubbles were exposed to pH 9 or above (at which daunorubicin typically degrades). The antibubbles preserved almost all the drug over 24 h, whereas most of it (∼90%) degraded in the unencapsulated form. Based on these initial results, antibubbles seem promising for delivering drugs to the intestine, as a proof-of-concept for oral chemotherapy.