Laboratory of Advanced Fibers , Empa, Swiss Federal Laboratories for Materials Science and Technology , Lerchenfeldstrasse 5 , CH-9014 St. Gallen , Switzerland.
Laboratory for Biointerfaces and Laboratory for Biomimetic Membranes and Textiles , Empa, Swiss Federal Laboratories for Materials Science and Technology , Lerchenfeldstrasse 5 , CH-9014 St. Gallen , Switzerland.
ACS Appl Mater Interfaces. 2020 Feb 12;12(6):7639-7649. doi: 10.1021/acsami.9b22808. Epub 2020 Jan 31.
Design and synthesis of nanostructured responsive gels have attracted increasing attention, particularly in the biomedical domain. Polymer chain configurations and nanodomain sizes within the network can be used to steer their functions as drug carriers. Here, a catalyst-free facile one-step synthesis strategy is reported for the design of pH-responsive gels and controlled structures in nanoscale. Transparent and impurity free gels were directly synthesized from trivinylphosphine oxide (TVPO) and cyclic secondary diamine monomers via Michael addition polymerization under mild conditions. NMR analysis confirmed the consumption of all TVPO and the absence of side products, thereby eliminating post purification steps. The small-angle X-ray scattering (SAXS) elucidates the nanoscale structural features in gels, that is, it demonstrates the presence of collapsed nanodomains within gel networks and it was possible to tune the size of these domains by varying the amine monomers and the nature of the solvent. The fabricated gels demonstrate structure tunability via solvent-polymer interactions and pH specific drug release behavior. Three different anionic dyes (acid blue 80, acid blue 90, and fluorescein) of varying size and chemistry were incorporated into the hydrogel as model drugs and their release behavior was studied. Compared to acidic pH, a higher and faster release of acid blue 80 and fluorescein was observed at pH 10, possibly because of their increased solubility in alkaline pH. In addition, their release in phosphate buffered saline (PBS) and simulated body fluid (SBF) matrix was positively influenced by the ionic interaction with positively charged metal ions. In the case of hydrogel containing acid blue 90 a very low drug release (<1%) was observed, which is due to the reaction of its accessible free amino group with the vinyl groups of the TVPO. In vitro evaluation of the prepared hydrogel using human dermal fibroblasts indicates no cytotoxic effects, warranting further research for biomedical applications. Our strategy of such gel synthesis lays the basis for the design of other gel-based functional materials.
设计和合成纳米结构响应性凝胶已经引起了越来越多的关注，特别是在生物医学领域。通过控制聚合物链构象和网络中的纳米域尺寸，可以对其作为药物载体的功能进行调控。本研究报道了一种无催化剂的简便一步法合成策略，用于设计在纳米尺度上具有 pH 响应性和可控结构的凝胶。在温和条件下，通过迈克尔加成聚合，三乙烯基氧化磷（TVPO）和环状仲二胺单体直接合成了透明且无杂质的凝胶。NMR 分析证实了所有 TVPO 的消耗和无副产物，从而省去了后纯化步骤。小角 X 射线散射（SAXS）阐明了凝胶的纳米结构特征，即凝胶网络中存在坍塌的纳米域，并且可以通过改变胺单体和溶剂的性质来调节这些域的尺寸。所制备的凝胶通过溶剂-聚合物相互作用和 pH 特异性药物释放行为表现出结构可调性。将三种不同大小和化学性质的阴离子染料（酸性蓝 80、酸性蓝 90 和荧光素）作为模型药物掺入水凝胶中，并研究了它们的释放行为。与酸性 pH 相比，在 pH 10 下观察到酸性蓝 80 和荧光素的释放量更高、更快，这可能是由于它们在碱性 pH 下的溶解度增加。此外，它们在磷酸盐缓冲盐水（PBS）和模拟体液（SBF）基质中的释放受到与带正电荷的金属离子的离子相互作用的积极影响。在含有酸性蓝 90 的水凝胶的情况下，观察到非常低的药物释放（<1%），这是由于其可及的游离氨基与 TVPO 的乙烯基反应所致。使用人真皮成纤维细胞对制备的水凝胶进行的体外评价表明没有细胞毒性作用，这为进一步的生物医学应用研究提供了依据。我们的这种凝胶合成策略为设计其他基于凝胶的功能材料奠定了基础。
