β-Glucan-based oral nano/micro delivery systems: harnessing dual immunomodulatory and microbiota-modulating properties for targeted therapy of cancer and inflammatory bowel disease.

The efficacy of oral drug delivery is often constrained by gastrointestinal physiological barriers and the hepatic first-pass effect, while conventional oral formulations lack the capability of targeted release at intestinal lesions, creating an urgent need for innovative functional delivery carriers. β-Glucan, an abundant natural polysaccharide, holds great potential for constructing intelligent oral nano/micro delivery systems, owing to its resistance to human digestive enzymes and its inherent dual immunomodulatory and microbiota-regulating properties. This carrier not only serves as an ideal protective vehicle but also bypasses the first-pass effect via M-cell-mediated lymphatic targeting and achieves site-specific drug release at pathological sites through its susceptibility to colonic microbiota enzymatic degradation. This review emphasizes the structural diversity, structure-activity relationships, and combined immunomodulatory/microbiota-modulating functions of β-glucan. It further explains how M-cell targeting and microbiota responsiveness are integrated to overcome gastrointestinal barriers for precise intestinal and systemic delivery. Recent advances in β-glucan-based nano/micro delivery systems for the treatment of cancer and inflammatory bowel disease are also highlighted. Finally, current challenges and future directions for β-glucan-based oral nano/micro delivery systems are outlined. In summary, the unique properties of β-glucan offer exciting new opportunities for targeted oral drug delivery.