Centre for Research in Medical Devices (CÚRAM), National University of Ireland, Galway, Ireland; Department of Mining-Metallurgy Engineering and Materials Science & POLYMAT, University of the Basque Country, Bilbao, Spain.
Centre for Research in Medical Devices (CÚRAM), National University of Ireland, Galway, Ireland.
Acta Biomater. 2018 Feb;67:21-31. doi: 10.1016/j.actbio.2017.12.014. Epub 2017 Dec 16.
Polymeric capsules exhibit significant potential for therapeutic applications as microreactors, where the bio-chemical reactions of interest are efficiently performed in a spatial and time defined manner due to the encapsulation of an active biomolecule (e.g., enzyme) and control over the transfer of reagents and products through the capsular membrane. In this work, catalase loaded polymer capsules functionalized with an external layer of tannic acid (TA) are fabricated via a layer-by-layer approach using calcium carbonate as a sacrificial template. The capsules functionalised with TA exhibit a higher scavenging capacity for hydrogen peroxide and hydroxyl radicals, suggesting that the external layer of TA shows intrinsic antioxidant properties, and represents a valid strategy to increase the overall antioxidant potential of the developed capsules. Additionally, the hydrogen peroxide scavenging capacity of the capsules is enhanced in the presence of the encapsulated catalase. The capsules prevent oxidative stress in an in vitro inflammation model of degenerative disc disease. Moreover, the expression of matrix metalloproteinase-3 (MMP-3), and disintegrin and metalloproteinase with thrombospondin motif-5 (ADAMTS-5), which represents the major proteolytic enzymes in intervertebral disc, are attenuated in the presence of the polymer capsules. This platform technology exhibits potential to reduce oxidative stress, a key modulator in the pathology of a broad range of inflammatory diseases.
Oxidative stress damages important cell structures leading to cellular apoptosis and senescence, for numerous disease pathologies including cancer, neurodegeneration or osteoarthritis. Thus, the development of biomaterials-based systems to control oxidative stress has gained an increasing interest. Herein, polymer capsules loaded with catalase and functionalized with an external layer of tannic acid are fabricated, which can efficiently scavenge important reactive oxygen species (i.e., hydroxyl radicals and hydrogen peroxide) and modulate extracellular matrix activity in an in vitro inflammation model of nucleus pulposus. The present work represents accordingly, an important advance in the development and application of polymer capsules with antioxidant properties for the treatment of oxidative stress, which is applicable for multiple inflammatory disease targets.
聚合物胶囊作为微反应器具有很大的治疗应用潜力，由于活性生物分子（例如酶）的封装以及对通过胶囊膜的试剂和产物转移的控制，感兴趣的生化反应以空间和时间定义的方式有效地进行。在这项工作中，通过层层方法使用碳酸钙作为牺牲模板来制造负载有过氧化氢酶的聚合物胶囊，该聚合物胶囊用单宁酸（TA）官能化。用 TA 官能化的胶囊对过氧化氢和羟基自由基具有更高的清除能力，这表明 TA 的外部层显示出内在的抗氧化特性，并且是增加所开发的胶囊的整体抗氧化能力的有效策略。此外，在存在封装的过氧化氢酶的情况下，胶囊的过氧化氢清除能力得到增强。胶囊可防止退行性椎间盘疾病的体外炎症模型中的氧化应激。此外，在聚合物胶囊存在的情况下，基质金属蛋白酶-3（MMP-3）和金属蛋白酶与血小板反应蛋白基序-5（ADAMTS-5）的表达均降低，这两种蛋白均代表椎间盘的主要蛋白水解酶。该平台技术具有减少氧化应激的潜力，氧化应激是包括癌症，神经退行性变或骨关节炎在内的多种炎症性疾病的主要病理调节剂。
