Cytosol-hydrogelled Chlorella enabling intestinal-targeted budesonide delivery for ulcerative colitis treatment.

Current oral enteric sustained-release formulations largely rely on polymer-based surface coatings and multi-matrix technologies, which increase manufacturing complexity and overall production costs. Here, we report a cytosol-hydrogelled Chlorella pyrenoidosa (CP) delivery system, named BUD-gel@CP, for sustained release of budesonide (BUD) in the intestinal tract. Unlike conventional microalgae-based drug delivery strategies, this system requires neither surface modification nor enteric coating. We find for the first time that the intrinsic proteins of CP, such as chlorophyll protein 47 (CP47), physically entrap BUD in aggregates under acidic gastric conditions, enabling the enteric release of BUD. Importantly, BUD is easily loaded into the cytosol of lyophilized CP in the presence of two FDA-approved excipients, which are Labrasol® as a solubilizer and Soluplus® to form a thermosensitivein situgel. Following oral administration, BUD-gel@CP showed prolonged drug retention in the intestinal tract and elevated BUD concentrations in intestinal tissues. In a DSS-induced colitis mouse model, BUD-gel@CP restored colon length and reduced TNF-α and IL-6 levels, showing improved therapeutic effects compared with non-hydrogelled control groups. Our findings suggest a novel paradigm for preparing an enteric sustained-release oral drug delivery system that utilizes natural food ingredients and commercially approved pharmaceutical excipients without surface coating or modification.