Construction strategies and cutting-edge advances in oral nanozyme delivery systems

Oral drug delivery is recognized as one of the most promising administration routes, primarily attributed to its superior patient compliance. Nevertheless, drugs encounter multiple physiological hurdles in the gastrointestinal tract, including the gastric acid barrier, enzymatic degradation, mucus barrier, and impaired epithelial absorption, which significantly compromise their bioavailability. Recent rapid advancements in nanotechnology have offered innovative approaches to address these challenges. This review systematically summarizes and discusses the latest research progress in oral nanodrug delivery systems, with a specific focus on elaborating delivery strategies based on diverse functional materials. These strategies encompass targeted delivery systems, environment-responsive release systems, microecological regulation systems, as well as multifunctional synergistic therapy and novel material systems. While inflammatory bowel disease serves as a primary model demonstrating their therapeutic potential, these sophisticatedly designed nanosystems also exhibit promising applications in the treatment of other conditions, including cancer, metabolic disorders, and oral infections such as periodontitis. They not only efficiently surmount gastrointestinal barriers but also enable the integration of diagnosis and therapy. Finally, this review provides an outlook on the future development directions of oral nanodrugs, emphasizing aspects of rational design, clinical translation, and personalized therapy.