Sustained-Release Enteric Formulations of Lactobacillus plantarum Based on Granulation Technology: Preparation and Therapeutic Evaluation in Acute Colitis

Background The clinical effectiveness of orally administered probiotics is often limited by poor survival during gastrointestinal transit and insufficient delivery to the intestinal site of action. Lactobacillus plantarum, a probiotic with anti-inflammatory potential, is highly sensitive to gastric acid and bile salts, diminishing its therapeutic efficacy for intestinal diseases. We developed a sustained-release enteric pellet formulation to enhance probiotic stability, promote targeted intestinal delivery, and evaluate its therapeutic efficacy in colitis. Results Pellets were prepared using low-temperature extrusion and coated with pH-responsive polymers (hydroxypropyl methylcellulose phthalate and Eudragit L100), creating a dual-protection barrier. Structural analysis revealed a cross-linked porous skeleton conducive to controlled release. In vitro tests confirmed gastric acid resistance and rapid release under intestinal conditions. In a dextran sulfate sodium-induced acute colitis mouse model, pellet-treated groups (both coatings) showed superior outcomes compared to uncoated probiotic powder. This included enhanced body weight recovery, reduced histopathological damage, downregulation of pro-inflammatory M1 macrophages, enhancement of anti-inflammatory M2 polarization, restoration of gut microbial diversity, and normalization of the Firmicutes to Bacteroidetes ratio. Conclusions The sustained-release enteric pellet system effectively protects Lactobacillus plantarum during gastrointestinal transit and achieves targeted intestinal release. Integrating mechanical shielding with pH-triggered dissolution significantly enhances probiotic bioavailability and therapeutic efficacy. This delivery platform represents a safe, scalable, and broadly applicable strategy for treating intestinal inflammatory diseases. Furthermore, the approach provides a versatile framework for delivering other probiotic strains or combinations.