Inflammation-Responsive Drug-Conjugated Dextran Nanoparticles Enhance Anti-Inflammatory Drug Efficacy

• DOI: 10.1021/acsami.8b08254
• Publication Date: 2018-08-01T14:21:54Z
• Authors: Sangeun Lee; Alexandra Stubelius; Naomi Hamelmann; Vincent Tran; Adah Almutairi
• Keywords: Proinflammatory cytokine; Conjugate

Stimuli-responsive nanoparticles (NPs) are especially interesting to enhance the drug delivery specificity for biomedical applications. With aim achieve a highly stable and inflammation-specific release, we designed reactive oxygen species (ROS)-responsive dextran–drug conjugate (Nap–Dex). By blending Nap–Dex with acid-sensitive acetalated dextran polymer, achieved dual-responsive NP high toward inflammatory environment. The environment not only has elevated ROS levels but also lower pH than healthy tissues, making suitable triggers target diseases. anti-inflammatory cyclooxygenase inhibitor naproxen was modified an ROS-responsive phenylboronic acid (PBA) conjugated onto dextran. units were functionalized up 87% naproxen. This resulted in complete release from polymer within 20 min at 10 mM H2O2. NPs reduced of proinflammatory cytokine IL-6 120 times more efficiently TNFα 6 free lipopolysaccharide (LPS)-activated macrophages. These additional effects found be mainly attributed ROS-scavenging effects. In addition, model cargo fluorescein diacetate released LPS-induced response vitro. We believe that conjugation using PBA can applied various drugs dextran-based materials enhanced efficacy, where this work demonstrates significance carbohydrates polymer–drug conjugates.