Advances in oral treatment of inflammatory bowel disease using protein-based nanoparticle drug delivery systems
Zhihao Lin, Ziheng Zhao, Xianrui Lin, Zhenlin Yang, Lin Wang, Rui Xi, Dingpei Long
Abstract
Inflammatory bowel disease (IBD) comprises chronic autoimmune disorders with significant morbidity, highlighting the need for advanced, noninvasive, targeted therapies. Protein-based nanoparticle drug delivery systems (PNP-DDSs) have emerged as promising platforms to overcome limitations of conventional IBD therapies by improving drug stability and bioavailability while enabling colon-specific delivery. This review systematically classifies PNP-DDSs derived from natural proteins (albumin, gelatin, silk fibroin, and plant-derived proteins) and discusses their design principles along with strategies for intestinal targeting, including particle size and surface charge modulation, stimuli-responsive release (triggered by pH, reactive oxygen species, or enzymes), and active targeting. It highlights recent preclinical advances with oral PNP-DDSs delivering curcumin, resveratrol, 5-aminosalicylic acid, quercetin, and other anti-inflammatory agents, which demonstrate the therapeutic potential of these nanoplatforms in IBD models. Despite promising preclinical outcomes, clinical translation of PNP-DDSs remains challenging due to patient heterogeneity, manufacturing scale-up difficulties, and safety concerns. Future progress will require interdisciplinary innovation and optimization of multi‑stimuli-responsive designs for precise and safe clinical application of PNP-DDSs in IBD management.