基于仿生两亲性壳聚糖衍生物的自组装纳米复合物用于蛋白质递药。
Self-assemblied nanocomplexes based on biomimetic amphiphilic chitosan derivatives for protein delivery.
机构信息
Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632, PR China.
Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632, PR China.
出版信息
Carbohydr Polym. 2015 May 5;121:115-21. doi: 10.1016/j.carbpol.2014.12.049. Epub 2015 Jan 2.
A bio-inspired nanocarrier was developed for protein delivery based on biodegradable amphiphilic chitosan derivative (DCA-PCCs) with hydrophilic cell membrane mimic phosphorylcholine (PC) and hydrophobic deoxycholic acid (DCA) moieties, which was synthesized via the combination of Atherton-Todd reaction and carbodiimide coupling reaction. Using bovine serum albumin (BSA) as model protein, it was found that DCA-PCCs with suitable degree of substitution of PC and DCA moieties can load proteins by forming nanocomplexes via a solvent evaporation method. The physicochemical characteristics of BSA/DCA-PCCs nanocomplexes were investigated by Zetasizer, atomic force microscopy (AFM) and Fourier-transform infrared (FT-IR) spectroscopy. In vitro biological evaluation revealed BSA/DCA-PCCs nanocomplexes as blank DCA-PCCs nanoparticles had excellent cytocompatibility and hemocompatibility mainly due to the presence of cell membrane mimic phosphorylcholine. BSA release results suggested BSA/DCA-PCCs nanocomplexes showed a sustained release behavior following first order exponential decay kinetics. The results indicated DCA-PCCs provided a promising approach for effectively delivering therapeutic proteins.
一种基于可生物降解的两亲性壳聚糖衍生物（DCA-PCCs）的仿生纳米载体被开发用于蛋白质递送，该衍生物具有亲水性细胞膜模拟物磷酸胆碱（PC）和疏水性脱氧胆酸（DCA）部分，通过 Atherton-Todd 反应和碳二亚胺偶联反应的结合合成。使用牛血清白蛋白（BSA）作为模型蛋白，研究发现具有合适取代度的 PC 和 DCA 部分的 DCA-PCCs 可以通过溶剂蒸发法形成纳米复合物来装载蛋白质。通过 Zetasizer、原子力显微镜（AFM）和傅里叶变换红外（FT-IR）光谱研究了 BSA/DCA-PCCs 纳米复合物的物理化学特性。体外生物学评价表明，由于存在细胞膜模拟物磷酸胆碱，BSA/DCA-PCCs 纳米复合物作为空白 DCA-PCCs 纳米颗粒具有优异的细胞相容性和血液相容性。BSA 释放结果表明，BSA/DCA-PCCs 纳米复合物表现出遵循一级指数衰减动力学的持续释放行为。结果表明，DCA-PCCs 为有效递送治疗性蛋白质提供了一种有前途的方法。
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