Disease‐Triggered Drug Release Effectively Prevents Acute Inflammatory Flare‐Ups,Achieving Reduced Dosing

For conditions with inflammatory flare‐ups, fast drug‐release from a depot is crucial to reduce cell infiltration and prevent long‐term tissue destruction. While this concept has been explored for chronic diseases, preventing acute inflammatory flares has not been explored. To address this issue, a preventative inflammation‐sensitive system is developed and applied to acute gout, a condition where millions of inflammatory cells are recruited rapidly, causing excruciating and debilitating pain. Rapid drug release is first demonstrated from a pH‐responsive acetalated dextran particle loaded with dexamethasone (AcDex‐DXM), reducing proinflammatory cytokines in vitro as efficiently as free drug. Then, using the air pouch model of gout, mice are pretreated 24 h before inducing inflammation. AcDex‐DXM reduces overall cell infiltration with decreased neutrophils, increases monocytes, and diminishes cytokines and chemokines. In a more extended prophylaxis model, murine joints are pretreated eight days before initiating inflammation. After quantifying cell infiltration, only AcDex‐DXM reduces the overall joint inflammation, where neither free drug nor a conventional drug‐depot achieves adequate anti‐inflammatory effects. Here, the superior efficacy of disease‐triggered drug‐delivery to prevent acute inflammation is demonstrated over free drug and slow‐release depots. This approach and results promise exciting treatment opportunities for multiple inflammatory conditions suffering from acute flares.