Bio-based pH-responsive double emulsions with controllable stability for enhanced oral delivery of probiotics

Probiotics play an important role in human health, but their final viability in the gut is often limited due to many harsh living conditions. A double emulsion is a suitable choice for live probiotic encapsulation and protection due to its liquid state and compartmentalized microstructure. Herein, we report a pH-responsive water-in-oil-in-water (W 1 /O/W 2 ) double emulsion, prepared via a two-step process, to enhance oral probiotic delivery. In the external aqueous phase, sodium caseinate (NaCas) and sodium alginate (SA) acted as synergistic food-grade stabilizers. NaCas provided interfacial activity, while SA increased continuous phase viscosity and imparted shear-thinning behavior, which facilitated emulsification and suppressed droplet mobility during storage. Additionally, NaCas–SA mixture formed a softer, more dissipative interfacial film than NaCas alone, reducing droplet coalescence. Importantly, the system exhibited dual pH-responsive behavior. Under acidic gastric conditions, it underwent rapid in situ gelation, where strong complexation between SA and NaCas strengthened the hydrogel network and robustly immobilized the double emulsion droplets. Conversely, upon transfer to alkaline intestinal conditions, the network disassembled, causing hydrogel dissolution and progressive droplet disintegration for controlled probiotic release. In vitro simulated digestion confirmed the protective efficiency. Unencapsulated probiotics showed substantial viability loss, and a conventional NaCas-only emulsion offered limited protection. In contrast, the pH-responsive NaCas–SA double emulsion preserved probiotic viability with minimal loss. Therefore, these findings support the potential of this system as a promising pH-responsive platform for efficient gut-targeted probiotic delivery.