基于聚(谷氨酸-酪氨酸-丙氨酸)嵌段共聚物的纳米药物载体制备与药物释放行为研究

Preparation and Drug Release Behavior of Nano-drug Carrier Based on Poly(glutamate-tyrosine-alanine)Block Copolymer

双亲性聚合物以其独特的物理结构和化学性质在生物医学,尤其在药物缓释领域具有重要的应用前景。本文首先设计并合成了具有亲疏水性的聚(天冬氨酸-酪氨酸-丙氨酸)嵌段聚合物,其结构通过红外光谱(FT-IR)与核磁共振氢谱(^(1)H NMR)的表征;其次,基于该嵌段聚合物通过自组装的方式对模型药物阿霉素进行了包载,构建了具有pH响应的药物纳米载体,采用扫描电子显微镜(SEM)与采用激光粒度仪(DLS)表征了载药纳米粒子的形貌、粒径大小及分布。研究表明,载药纳米粒子在溶液中呈现球形,其粒径小于220nm,且具有明显的pH响应性,在酸性条件下的释放效果明显高于中性和碱性条件。此外,体外细胞毒性实验表明,该聚氨基酸材料对L-929细胞无毒性。

Due to the unique physical structure and chemical properties,amphiphilic polymers have an important role in biomedicine,especially in the field of drug release.In this study,a new block copolymer poly(aspartate-tyrosine-alanine)was synthesized by ring-opening polymerization,and its structure was characterized by FT-IR and ^(1)H-NMR.The model drug doxorubicin was loaded by self-assembly based on the block polymer,and the drug nanocarriers with pH response were constructed.The morphology,particle size and distribution of drug-loaded nanoparticles were characterized by scanning electron microscopy(SEM)and dynamic light scattering(DLS),respectively.The results showed that the particle size of drug-loaded nanoparticles in solution is less than 220nm and had obvious pH response.The release effect of drug-loaded nanoparticles in acidic conditions is obviously higher than that in neutral and alkaline conditions.In addition,in vitro cytotoxicity experiments showed that the polyamino acid material was not toxic to L-929 cells.