Multishell Colloidosome Platform with Sequential Gastrointestinal Resistance for On‐Demand Probiotic Delivery

Abstract Probiotic‐based oral therapy can potentially prevent and treat diseases by regulating the balance of intestinal flora. However, significant loss of viability and bioactivity of probiotics before reaching the colon results in low delivery efficiency and therapeutic effects, which limits their clinical applications. Here, this work proposes a multishell colloidosome (MSC) platform with sequential gastrointestinal resistance for on‐demand probiotic delivery based on biomimetic mineralization and microfluidic technology. Notably, the viability of the decorated probiotics increases 280‐fold compared to that of free bacteria during preservation. Because of the sequential gastrointestinal resistance of MSC, encapsulated probiotics exhibit high viability (61%) under continuous exposure to extreme acidity, bile salt erosion, and enzymatic action, whereas free bacteria have a viability of 0%. Moreover, in vitro and in vivo studies reveal that MSC mainly releases probiotics in the colon and improves colonic colonization by probiotics to maintain the integrity of the intestinal barrier and regulate the balance of intestinal flora. Consequently, MSC significantly improves the therapeutic effect on colitis in mice. The MSC platform provides a promising delivery strategy to enhance the efficacy of orally administered probiotics.