壳聚糖
活性氧
材料科学
过氧化氢
右旋糖酐
氧化应激
炎症性肠病
生物物理学
复合数
纳米颗粒
纳米技术
疾病
医学
化学
复合材料
生物化学
生物
病理
作者
Serena Bertoni,Zehua Liu,Alexandra Correia,João P. Martins,Antti Rahikkala,Flavia Fontana,Marianna Kemell,Dongfei Liu,Beatrice Albertini,Nadia Passerini,Wei Li,Hélder A. Santos
标识
DOI:10.1002/adfm.201806175
摘要
Abstract Oxidative stress and abnormally high levels of reactive oxygen species (ROS) play an essential role in the pathogenesis and progression of inflammatory bowel disease (IBD). Oxidation‐responsive nanoparticles (NPs) are formulated from a phenylboronic esters‐modified dextran (OxiDEX) that degrades selectively in response to hydrogen peroxide (H 2 O 2 ). OxiDEX NPs are coated with chitosan and encapsulated in a pH‐sensitive polymer to produce nano‐in‐micro composites. The microparticles are spherical with homogeneous particle size (53 ± 3 µm) and maintain integrity at acidic pH, preventing the premature release of the NPs in gastric conditions. The degradation of NPs is highly responsive to the level of H 2 O 2 , and the release of the drug is sustained in the presence of physiologically relevant H 2 O 2 concentrations. The presence of chitosan on the particles surface significantly enhances NPs stability in intestinal pH and their adhesion on the intestinal mucosa. Compared to a traditional enteric formulation, this formulation shows tenfold decreased drug permeability across C2BBe1/HT29‐MTX cell monolayer, implying that lower amount of drug would be absorbed to the blood stream and, therefore, limiting the undesired systemic side effects. Based on these results, a successful nano‐in‐micro composite for targeted therapy of IBD is obtained by combination of the responsiveness to pH and ROS.
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