Pan Panpan, Chen Jingdi, Fan Tiantang, Hu Yimin, Wu Tao, Zhang Qiqing
Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002, China.
Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002, China.
Colloids Surf B Biointerfaces. 2016 Apr 1;140:50-59. doi: 10.1016/j.colsurfb.2015.12.027. Epub 2015 Dec 21.
This research aims to prepare the biphasic-induced magnetic composite microcapsules (BIMCM) as a promising environmental stimuli-responsive delivery vehicle to dispose the problem of drug burst effect. The paper presented a novel automated in situ click technology of magnetic chitosan/nano hydroxyapatite (CS/nHA) microcapsules. Fe3O4 magnetic nanoparticles (MNP) and nHA were simultaneously in situ crystallized by one-step process. Icariin (ICA), a plant-derived flavonol glycoside, was combined to study drug release properties of BIMCM. BIMCM were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and Thermal gravimetric analysis/Differential Scanning Calorimetry(TGA/DSC) in order to reveal their component and surface morphology as well as the role of the in situ generated Fe3O4 MNP and nHA. The magnetic test showed the BIMCM were super-paramagnetic. Both in situ generated Fe3O4 MNP and nHA serve as stable inorganic crosslinkers in BIMCM to form many intermolecular crosslinkages for the movability of the CS chains. This makes ICA loaded microcapsules take on a sustained release behavior and results in the self-adjusting of surface morphology, decreasing of swelling and degradation rates. In addition, in vitro tests were systematically carried out to examine the biocompatibility of the microcapsules by MTT test, Wright-Giemsa dying assay and AO/EB fluorescent staining method. These results demonstrated that successful introduction of the in situ click Fe3O4 MNP provided an alternative strategy because of magnetic sensitivity and sustained release. As such, the novel ICA loaded biphasic-induced magnetic CS/nHA/MNP microcapsules are expected to find potential applications in drug delivery system for bone repair.
本研究旨在制备双相诱导磁性复合微胶囊（BIMCM），作为一种有前景的环境刺激响应型给药载体，以解决药物突释效应问题。本文提出了一种新型的磁性壳聚糖/纳米羟基磷灰石（CS/nHA）微胶囊自动原位点击技术。通过一步法使Fe3O4磁性纳米颗粒（MNP）和nHA同时原位结晶。结合植物来源的黄酮醇苷淫羊藿苷（ICA），研究BIMCM的药物释放特性。通过傅里叶变换红外光谱（FTIR）、X射线衍射（XRD）、X射线光电子能谱（XPS）、扫描电子显微镜（SEM）和热重分析/差示扫描量热法（TGA/DSC）对BIMCM进行表征，以揭示其组成和表面形态，以及原位生成的Fe3O4 MNP和nHA的作用。磁性测试表明BIMCM具有超顺磁性。原位生成的Fe3O4 MNP和nHA在BIMCM中均作为稳定的无机交联剂，形成许多分子间交联，以限制CS链的移动性。这使得负载ICA的微胶囊呈现出缓释行为，并导致表面形态的自我调节、溶胀和降解速率的降低。此外，通过MTT试验、瑞氏-吉姆萨染色法和AO/EB荧光染色法系统地进行了体外试验，以检测微胶囊的生物相容性。这些结果表明，原位点击Fe3O4 MNP的成功引入提供了一种基于磁敏感性和缓释性的替代策略。因此，新型负载ICA的双相诱导磁性CS/nHA/MNP微胶囊有望在骨修复药物递送系统中找到潜在应用。
