pH and Reactive Oxygen Species‐Sequential Responsive Nano‐in‐Micro Composite for Targeted Therapy of Inflammatory Bowel Disease,Advanced Functional Materials

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pH and Reactive Oxygen Species‐Sequential Responsive Nano‐in‐Micro Composite for Targeted Therapy of Inflammatory Bowel Disease
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2018-10-16 , DOI: 10.1002/adfm.201806175
Serena Bertoni _{1,

2} , Zehua Liu ₁ , Alexandra Correia ₁ , João Pedro Martins ₁ , Antti Rahikkala ₁ , Flavia Fontana ₁ , Marianna Kemell ₃ , Dongfei Liu _{1,

4} , Beatrice Albertini ₂ , Nadia Passerini ₂ , Wei Li ₁ , Hélder A. Santos _{1,

4}

Affiliation

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 (H₂O₂). 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 H₂O₂, and the release of the drug is sustained in the presence of physiologically relevant H₂O₂ 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.

中文翻译：

pH和活性氧物种-顺序响应纳米-微复合材料用于炎性肠病的靶向治疗

氧化应激和异常高水平的活性氧（ROS）在炎症性肠病（IBD）的发病机理和进展中起着至关重要的作用。氧化响应纳米颗粒（NPs）由苯基硼酸酯改性的葡聚糖（OxiDEX）配制而成，该葡聚糖可响应过氧化氢（H ₂ O ₂）选择性降解。OxiDEX NP涂有壳聚糖，并封装在对pH敏感的聚合物中，以生产纳米级复合材料。微粒是球形的，具有均一的粒径（53±3 µm），并且在酸性pH下保持完整性，从而防止了在胃部条件下NP的过早释放。NPs的降解高度响应H ₂ O ₂的水平，并且在生理上相关的H ₂ O ₂浓度存在下，药物的释放得以持续。壳聚糖在颗粒表面的存在显着增强了NP在肠道pH值中的稳定性以及它们在肠粘膜上的附着力。与传统的肠溶制剂相比，该制剂在C2BBe1 / HT29-MTX细胞单层上的药物渗透性降低了十倍，这意味着较少量的药物将被吸收到血流中，因此限制了不良的全身性副作用。基于这些结果，结合对pH和ROS的响应性，获得了成功的用于IBD靶向治疗的纳米级复合材料。

更新日期：2018-10-16

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