Sustained-release enteric formulations of Lactiplantibacillus plantarum based on granulation technology: preparation and therapeutic evaluation in acute colitis

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. Lactiplantibacillus plantarum, a probiotic with anti-inflammatory potential, is highly sensitive to gastric acid and bile salts, diminishing its therapeutic efficacy for intestinal diseases. The aim of this study was to develop an enteric sustained-release granule formulation of Lactobacillus plantarum to enhance probiotic stability, promote targeted intestinal delivery, and evaluate its therapeutic efficacy in the treatment of colitis. Sustained-release enteric pellets containing Lactiplantibacillus plantarum were prepared using a low-temperature wet granulation and extrusion process, followed by coating with pH-responsive polymers (HPMCP or Eudragit L100). In vitro release behavior was evaluated in simulated gastric and intestinal fluids. Therapeutic efficacy was assessed in a dextran sulfate sodium (DSS)-induced acute colitis mouse model using histopathology, macrophage polarization, and gut microbiota analysis. The sustained-release granules exhibited a narrow and uniform particle size distribution, with diameters ranging from 40 to 80 mesh (180–425 μm). More than 85% of the granules were distributed within the 40–60 mesh fraction (250–425 μm). The micropellets exhibited adequate mechanical strength for handling and processing. The enteric-coated micropellets showed pronounced acid resistance, retaining over 70% bacterial viability after 2 h in simulated gastric fluid, compared with <30% for free bacterial powder. In simulated intestinal fluid, the micropellets achieved sustained bacterial release for over 2 h. In DSS-induced colitis mice, treatment with the granule formulations resulted in a more pronounced trend toward histological recovery. Moreover, the sustained-release granules promoted M2 macrophage polarization and partially restored gut microbial diversity, as evidenced by normalization of the Firmicutes-to-Bacteroidetes ratio. The sustained-release enteric pellet system effectively protects Lactiplantibacillus plantarum during gastrointestinal transit and achieves targeted intestinal release. Integrating mechanical shielding with pH-triggered dissolution significantly enhances probiotic gastrointestinal survival 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.