Biomaterials Enhance Delivery of Inflammasome Inhibitors for Inflammatory Diseases

Inflammasomes are crucial multi-protein complexes that play a central role in the body's innate immune response, triggering inflammation by activating pro-inflammatory cytokines like IL-1β and IL-18. Dysregulated inflammasome activity is implicated in a wide array of chronic inflammatory and autoimmune conditions, including rheumatoid arthritis, Crohn's disease, and neurodegenerative disorders. While small molecule inflammasome inhibitors show promise, their systemic administration often leads to off-target effects and poor bioavailability at disease sites. This review addresses the critical need for improved delivery strategies, specifically exploring how biomaterials can be engineered to precisely deliver inflammasome inhibitors, enhancing therapeutic efficacy and reducing systemic toxicity.

The review consistently highlighted that biomaterial-encapsulated inhibitors significantly improved drug pharmacokinetics and therapeutic outcomes. Studies showed that nanoparticle-delivered MCC950 achieved a 2.5-fold higher local concentration in inflamed tissues compared to free drug, leading to a 40-60% reduction in IL-1β and IL-18 secretion in macrophage cultures (p<0.01). In murine models of acute lung injury, hydrogel-delivered glyburide reduced lung inflammation by over 50% (p<0.001) compared to systemic administration, with significantly fewer off-target effects. Furthermore, microsphere-based delivery of NLRP3 inhibitors extended therapeutic efficacy by up to 7 days post-administration, whereas free inhibitors typically required daily dosing. > The most compelling evidence suggested that functionalized biomaterials could reduce systemic inhibitor dosage by up to 80% while maintaining or enhancing local therapeutic effect, significantly mitigating systemic toxicity concerns.