Lee Ai-Wei, Chang Pao-Lung, Liaw Shien-Kuei, Lu Chien-Hsing, Chen Jem-Kun
Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 106, Taiwan.
Department of Materials and Science Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan.
Polymers (Basel). 2022 Sep 1;14(17):3611. doi: 10.3390/polym14173611.
Poly(methacrylic acid) (PMAA) brushes were tethered on a silicon surface possessing a 500-nm hole array via atom transfer radical polymerization after the modification of the halogen group. Dextran-biotin (DB) was sequentially immobilized on the PMAA chains to obtain a P(MAA-DB) brush surrounding the hole edges on the silicon surface. After loading antibiotics inside the holes, biphenyl-4,4'-diboronic acid (BDA) was used to cross-link the P(MAA-DB) chains through the formation of boronate esters to cap the hole and block the release of the antibiotics. The boronate esters were disassociated with reactive oxygen species (ROS) to open the holes and release the antibiotics, thus indicating a reversible association. The total amount of drug inside the chip was approximately 52.4 μg cm, which could be released at a rate of approximately 1.6 μg h cm at a ROS concentration of 10 nM. The P(MAA-DB) brush-modified chip was biocompatible without significant toxicity toward L929 cells during the antibiotic release. The inflammation-triggered antibiotic release system based on a subcutaneous implant chip not only exhibits excellent efficacy against bacteria but also excellent biocompatibility, recyclability, and sensitivity, which can be easily extended to other drug delivery systems for numerous biomedical applications without phagocytosis- and metabolism-related issues.
在对硅表面进行卤基修饰后，通过原子转移自由基聚合将聚甲基丙烯酸（PMAA）刷固定在具有500纳米孔阵列的硅表面上。将葡聚糖 - 生物素（DB）依次固定在PMAA链上，以在硅表面的孔边缘周围获得P（MAA - DB）刷。在孔内装载抗生素后，使用联苯 - 4,4'-二硼酸（BDA）通过形成硼酸酯来交联P（MAA - DB）链，从而封闭孔并阻止抗生素释放。硼酸酯与活性氧（ROS）解离以打开孔并释放抗生素，从而表明存在可逆缔合。芯片内药物的总量约为52.4μg/cm²，在ROS浓度为10 nM时，药物可以以约1.6μg/（h·cm²）的速率释放。在抗生素释放过程中，P（MAA - DB）刷修饰的芯片具有生物相容性，对L929细胞无明显毒性。基于皮下植入芯片的炎症触发抗生素释放系统不仅对细菌具有优异的疗效，而且具有优异的生物相容性、可回收性和敏感性，可轻松扩展到其他药物递送系统，用于众多生物医学应用，而不存在与吞噬作用和代谢相关的问题。
