氨基种类与亲/疏水比例对聚己内酯共聚物抗菌机理的作用研究

Cationic center and linear alkyl side-chains are essential structure to traditional antimicrobial polymers. Recently, studies on antibacterial polymers which do not contain linear alkyl side-chains broadened scope of the material. The effect of cationic species and hydro-philic/-phobic ratio on the antimicrobial mechanism for the polymers without linear alkyl side-chains are not discussed. In addition, the hydro-philic/-phobic ratio was generally regulated by the amount of water-soluble positively charged group. It is difficult to discern the priority factor for the antibacterial effect. Our previous work has shown that polycaprolactone (PCL) could serve as a hydrophobic segment in the antimicrobial polymer bearing no alkyl side-chains. Base on the preliminary work, PCL copolymers whose cationic and hydro-philic/-phobic ratio could be independently regulated will be synthesized. The copolymer will be applied to study: 1. effect of primary, tertiary amine groups and quaternary ammonium groups towards the interaction mechanism between the copolymer and bacteria; 2. effect of hydro-philic/-phobic ratio towards the antimicrobial mechanism. Cytocompatibility and hemocompatibility will also be evaluated. The antimicrobial mechanism of the PCL copolymers without alkyl side-chains will be investigated at both material and cellular levels.

正电荷、直链烷烃侧基是传统抗菌聚合物的必要结构。最近关于无直链烷烃侧基的抗菌聚合物的研究，丰富了抗菌聚合物的种类。然而，正电荷基团种类、聚合物的亲/疏水比例对无直链烷烃侧基共聚物抗菌机理的影响尚不明确。此外，以水溶性正电基团调控聚合物的亲/疏水比例的传统方法，难以确定影响聚合物抗菌效果的优先因素。我们的前期工作表明，聚己内酯可以作为无直链烷烃侧基的抗菌聚合物的疏水段，且随聚己内酯共聚物中亲水伯氨基比例增加，共聚物的抗菌性能增强。基于前期工作，本项目拟通过合成可以独立调控正电荷性质、亲/疏水比例的无直链烷基侧基的聚己内酯共聚物，开展如下研究：1.研究伯氨基、叔氨基和季铵盐基团对共聚物抗菌机理的影响；2.研究亲/疏水比例对共聚物的抗菌机理的影响。并考察无直链烷基侧基聚己内酯共聚物的细胞相容性、血液相容性。在材料和细胞水平上多层次研究无直链烷基侧基聚己内酯共聚物的抗菌机理。

抗菌聚合物一般通过疏水烷烃片段调控亲/疏水比，但疏水烷烃的引入需要复杂的化学反应。不含烷烃侧基的抗菌聚合物合成简单，但亲/疏水比和阳离子种类对其抗菌性能的影响尚不明确。本项目提出利用功能化聚（己内酯-co-碳酸酯）研究亲/疏水比、利用功能化壳寡糖研究氨基种类分别对不含烷烃侧基聚合物抗菌性能的影响。本项目首先合成了含潜氨基的碳酸酯单体，通过与己内酯共聚和获得不含烷烃侧基的功能化聚（己内酯-co-碳酸酯）。调控碳酸酯单体与己内酯的投料比可以调控聚（己内酯-co-碳酸酯）的亲/疏水比。随亲/疏水比增大，聚（己内酯-co-碳酸酯）以破坏细胞膜机理实现抗菌性增强。壳寡糖是研究氨基种类对不含烷烃侧基聚合物抗菌性能影响的良好平台。利用聚甲基丙烯酰精氨酸作为载体可以实现壳寡糖的延长释放，实现长效抗菌。进一步通过一步法甲基化反应合成叔氨基壳寡糖，元素分析、核磁波谱证明甲基化反应后壳寡糖中的伯氨基几乎完全转化为叔氨基。叔胺化壳寡糖的抗菌性较壳寡糖提高4-32倍。本项目研究成果表明高亲/疏水比和叔氨基有利于提高不含烷烃侧基聚合物的抗菌性能。