Cyclodextrin-Derived Macromolecular Therapies for Inflammatory Diseases

Inflammation is an essential physiological defense mechanism against harmful stimuli, yet dysregulated inflammatory responses are closely associated with the pathogenesis of numerous acute and chronic diseases. Recent advances highlight the remarkable anti-inflammatory potential of bioactive macromolecules, particularly cyclodextrins (CDs) and their engineered derivatives, which are emerging as promising therapeutic agents. This review systematically introduces different CDs and CD-derived macromolecules that demonstrate anti-inflammatory properties, with emphasis on their molecular mechanisms of action. Native CDs exhibit direct therapeutic effects through host-guest interactions, enabling selective sequestration of pathogenic components such as cholesterol crystals and proteins that drive inflammatory cascades. Moreover, chemically modified CD derivatives incorporating functional groups demonstrate enhanced capabilities in neutralizing inflammatory mediators and modulating immune cell responses. This work further discusses the expanding therapeutic applications of these macromolecules across diverse inflammatory conditions, ranging from acute tissue injuries to chronic autoimmune disorders. Finally, this work critically analyzes the crucial challenges and emerging opportunities in translating CD-based macromolecular therapies into clinical practice, addressing key considerations in biocompatibility, targeted delivery, and therapeutic efficacy optimization.