纳米碳-粘土/聚合物抗菌智能复合凝胶的构建及性能调控

Smart composite hydrogels show great potential application for control delivery of antibacterial drugs due to their special environmental responses. However, the wide application of smart composite hydrogels is now limited because of their low strength, slow response, poor drug-carrying performance and relatively bad biocompatibility. In this project, composite hydrogel carriers are going to be prepared by grafted temperature/pH sensitive polymers on the surfaces of nanocarbon-clay composites, and then antibacterial smart composite hydrogels with core-shell structure will also be fabricated by loading antibacterial drugs on the carriers. The influences of compositional structure of raw materials and technological conditions on the compositional structure of carriers and antibacterial smart composite hydrogels will be studied systematically, and their compositional structure control will be obtained. The inner relationship between compositional structure of carriers and their physicochemical property, mechanical properties, drug-carrying performance, environmental (temperature, pH and near-infrared light) responses, and cytotoxicity will be deeply studied, and its drug loading mechanism is gonging to be grasped, as well the carriers and antibacterial smart composite hydrogels with excellent combination property. The change rules of physicochemical property, environmental response speed, drug release characteristics and antibacterial activity for antibacterial smart composite hydrogels will be researched thoroughly. The dynamic models of drug release will be established, and the control delivery of antibacterial drugs is going to be realized under the condition of environmental cooperative and quick tripling responses. The study is in favor of improving the basic research levels of drug carriers for our country, and providing a new approach and idea for developing new antibacterial smart hydrogels with high-performance.

智能水凝胶由于其独特环境响应性在抗菌药物控释领域显示广阔应用潜力，但目前尚存在强度低、响应速度慢、载药性能欠佳、生物相容性较差等缺点，限制其广泛应用。本项目设计以纳米碳材料-粘土复合物为基体，在其表面接枝温度/pH敏感聚合物并凝胶化获得复合凝胶载体，然后负载抗菌药物构建新型核壳结构抗菌智能复合凝胶。系统研究原料组成结构、工艺条件对载体和抗菌智能复合凝胶组成结构的影响规律，获得其组成结构调控方法；深入研究载体组成结构与其理化性质、力学性能、载药性能、环境（温度、pH和近红外光）响应性、细胞毒性的内在关系，弄清载药机制，构建综合性能优异的载体和抗菌智能复合凝胶；进一步研究抗菌智能复合凝胶的理化性能、环境响应速度、释药性能和抗菌活性的变化规律，建立释药动力学模型，实现环境三重快速协调响应下的抗菌药物控释。该研究有利于提高我国药物载体基础研究水平，并为发展新型高性能抗菌智能凝胶提供新途径和新思路。

针对目前水凝胶存在强度低、载/释药性能欠佳，结构性能难以调控等技术瓶颈，本项目设计制备多个系列pH敏感、温敏和光热响应的抗菌及多功能智能水凝胶和复合材料。通过研究，获得以下一些重要研究结果：（1）以N-异丙基丙烯酰胺分别与乙烯化羧化壳聚糖或丙烯酰胺共聚、乙烯化氧化石墨烯或累托石为改性剂合成两类新型温敏水凝胶。发现改变CG、GM或REC用量可调控其LCST和理化性能，负载盐酸环丙沙星后在生理温度37℃下药物具有较完全释放，并显示良好生物相容性和可调抗菌活性，有望在伤口敷料抗微生物感染方面应用。（2）以N,N-二乙基丙烯酰胺、羟甲基丙烯酰胺为单体，碳纳米管和改性壳聚糖为改性剂，合成结构性能可控的两类新型温敏及光热智能水凝胶。发现其LCST可调控至37.9℃，并显示良好压缩性和生物相容性，可通过水凝胶中药物更完全释放来抑制伤口感染和发炎。（3）以聚乙烯醇、天然多糖、丝素蛋白、氧化石墨烯、合成皂石和盐酸环丙沙星为原料，制备两类结构性能可控的近红外响应智能载药水凝胶，发现其释药速率可通过近红外光调控，且生物相容性和机械性能优异，在抗微生物感染方面显示良好应用潜力。（4）以明胶、氧化葡聚糖、双键化明胶、丙烯酰胺、单宁酸/铁离子螯合物、和Cu2O-单宁酸纳米粒为原料制备两类抗菌水凝胶，均显示pH敏感可控抗菌抗炎性和近红外协同增效性，有利于防止伤口感染和降低微生物耐药性。(5)开发具有Ⅰ型异质结的AgBiS2 QDs/g-C3N4 复合材料。发现由于其增强的光催化效应，导致由于细菌胞内活性氧水平迅速升高而使细菌死亡，实现在可见光照射下高效杀灭金黄色葡萄球菌效果，有望应用在生物医用领域的抗耐药菌感染。（6）以邻苯二酚修饰壳聚糖、多巴胺官修饰聚吡咯和明胶等制备两类新型智能水凝胶，显示良好载药、抗菌、抗氧化和光热性能，且血液相容性优异，在医用敷料和美容领域显示广阔应用前景。通过研究，发表SCI和EI收录论文25篇，获授权发明专利2件，培养博士后1 名、博士生1名、硕士生10名。