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

Abstract

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.

Anti-inflammatory activity of curcumin-loaded tetrahedral framework nucleic acids on acute gouty arthritis

“…Usually, for these diseases with the repeated onset of acute inflammation, the curative effect of drugs that can be effectively released by the drug delivery system is better than that of drugs alone. And this kind of treatment can reduce the drug dose, thereby reducing unnecessary side effects [59]. At present, NSAIDs, corticosteroids, and colchicine can effectively relieve inflammatory symptoms well in general [7].…”

Monosodium urate crystals regulate a unique JNK-dependent macrophage metabolic and inflammatory response

“…Dermal air pouches were established by injecting mice dorsally subcutaneously with 3 mL filtered (0.20 mm) air on day 0 and 3 (Sanchez-Lopez et al, 2019b;Stubelius et al, 2018). On day 7, BAY-876 (5 mg/kg, in 2.5%DMSO/40%PEG/5%Tween80) or JNK inhibitor (15 mg/kg, in 2.5%DMSO/30%PEG/10%Tween80) were injected intrapouch and one hour later, MSUc were injected (3 mg in 0.5 mL PBS).…”

Dual Functional Monocytes Modulate Bactericidal and Anti‐Inflammation Process for Severe Osteomyelitis Treatment

“…While, the administration of the antibiotics increases the incidence of drug‐resistant form induction and the barriers along the road by systemically application diminishing their effectiveness . Though immunotherapy has been reported to facilitate infectious diseases, the cytokine storms or cytokine release syndrome induced by immune cell expansion will lead to unexpected adverse reactions ranging from mild nausea and fever, to life‐threatening multiple organ failure . Therefore, in addition to improving the bactericidal effects on pathogens, the ideal osteomyelitis treatment should take into account the inhibition of adverse and excessive inflammatory reactions thus promoting the bone tissue regeneration .…”