Department of Chemical Engineering, Izmir Institute of Technology, Izmir, Turkey.
Biomed Mater. 2019 May 17;14(4):044101. doi: 10.1088/1748-605X/ab1a04.
Despite the advancements in bone transplantation operations, inflammation is still a serious problem that threatens human health at the post-implantation period. Conventional antibiotic therapy methods may lead to some side effects such as ototoxicity and nephrotoxicity, especially when applied in high doses. Therefore, local drug delivery systems play a vital role in bone disorders due to the elimination of the disadvantages introduced by conventional methods. In the presented study, it was aimed to develop Vancomycin (VC) and Gentamicin (GC) loaded chitosan-montmorillonite nanoclay composites (CS/MMT) to provide required antibiotic doses to combat post-implantation infection. CS/MMT nanocomposite formation was supplied by microfluidizer homogenization and spherical drug carrier nanoparticles were obtained by electrospraying technique. Three factors; voltage, distance and flowrate were varied to fabricate spherical nanoparticles with uniform size. Emprical model was developed to predict nanosphere size by altering process variables. Nanospheres were characterized in terms of morphology, hydrodynamic size, zeta potential, drug encapsulation efficiency and release profile. Drug loaded nanospheres have been successfully produced with a size range of 180-350 nm. Nanocomposite drug carriers showed high encapsulation efficiency (80%-95%) and prolonged release period when compared to bare chitosan nanospheres. The drug release from nanocomposite carriers was monitored by diffusion mechanism up to 30 d. The in vitro release medium of nanospheres showed strong antimicrobial activity against gram-positive S. aureus and gram-negative E. coli bacteria. Furthermore, it was found that the nanospheres did not show any cytotoxic effect to fibroblast (NIH/3T3) and osteoblast (SaOS-2) cell lines. The results demonstrated that the prepared composite nanospheres can be a promising option for bone infection prevention at the post implantation period.
尽管骨移植手术取得了进步，但炎症仍然是一个严重的问题，在植入后期威胁着人类健康。传统的抗生素治疗方法可能会导致一些副作用，如耳毒性和肾毒性，尤其是在高剂量应用时。因此，局部药物递送系统在骨疾病中起着至关重要的作用，因为它消除了传统方法带来的缺点。在本研究中，旨在开发载万古霉素（VC）和庆大霉素（GC）的壳聚糖-蒙脱土纳米粘土复合材料（CS/MMT），以提供所需的抗生素剂量来对抗植入后感染。CS/MMT 纳米复合材料的形成由微流均质提供，通过电喷雾技术获得球形药物载体纳米粒子。通过改变电压、距离和流速三个因素来制备具有均匀尺寸的球形纳米粒子。通过改变工艺变量来开发经验模型来预测纳米球的尺寸。纳米球的形态、水动力粒径、Zeta 电位、药物包封效率和释放曲线进行了特征描述。成功制备了尺寸范围为 180-350nm 的载药纳米球。与壳聚糖纳米球相比，纳米复合药物载体表现出较高的包封效率（80%-95%）和延长的释放时间。通过扩散机制监测纳米复合载体中的药物释放，可达到 30d。纳米球的体外释放介质对革兰氏阳性金黄色葡萄球菌和革兰氏阴性大肠杆菌具有很强的抗菌活性。此外，还发现纳米球对成纤维细胞（NIH/3T3）和成骨细胞（SaOS-2）细胞系没有任何细胞毒性作用。结果表明，所制备的复合纳米球可作为植入后期预防骨感染的一种有前途的选择。
