Polysaccharide-Derived Drug Delivery Systems: Therapeutic Potential in Rheumatoid Arthritis—A Review

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovial inflammation, synovial hyperplasia, and progressive joint destruction and remains a major clinical challenge. Polysaccharide-derived delivery platforms have attracted widespread attention for RA precision therapy owing to their natural origin, excellent biocompatibility, and tailorable functionality; however, existing reviews generally focus on single material or carrier types and provide limited cross-comparison of carrier architectures and translational considerations. This review systematically evaluates recent advances in polysaccharide derivative design strategies and delivery system innovations for RA management. We first elaborate on how chemical modifications confer multi-responsive properties (pH-, reactive oxygen species [ROS]-, and enzyme-triggered release) and how diversified morphologies (hydrogels, microspheres, microneedles, vesicles) enable spatiotemporally controlled drug delivery in inflamed joints. Critical analysis highlights several translational barriers, including limited in vivo retention, insufficient pharmacokinetic and biodistribution data, and challenges associated with scale-up manufacturing and reproducibility. Looking forward, future development should integrate biomimetic design, rational multi-component optimization, and advanced manufacturing technologies to improve the stability, controllability, and translational feasibility of polysaccharide-based RA delivery systems. This review provides an integrated, translation-focused perspective that bridges material engineering and clinical pathological demands, guiding the development of next-generation polysaccharide-based RA therapies.