Dataset Information

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.

SUBMITTER: Stubelius A

PROVIDER: S-EPMC6165597 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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

Stubelius Alexandra A Sheng Wangzhong W Lee Sangeun S Olejniczak Jason J Guma Monica M Almutairi Adah A

Small (Weinheim an der Bergstrasse, Germany) 20180715 32

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. R ...[more]

PMID: 30009516

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Dataset Information

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

Publications

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

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