甲氧基聚乙二醇末端功能化修饰壳聚糖的合成方法比较

Comparative study on terminal functionalization methods of methoxy poly(ethylene glycol)to modify chitosan

为提高壳聚糖作为体内移植材料的抗蛋白吸附性能和纳米药物载体的长循环能力,对壳聚糖进行甲氧基聚乙二醇(MPEG)改性修饰。通过考察MPEG末端功能化修饰壳聚糖的4种不同方法,包括MPEG末端羧基化法、乙酸酐氧化醛基化法、催化氧化醛基化法以及Williamson亲核取代醛基化法,从中筛选出反应条件可控、转化率高、产物稳定性好和重复性好的Williamson亲核取代醛基化合成方法作为MPEG修饰壳聚糖的主要手段。将MPEG末端功能化并接枝到壳聚糖骨架上,制备了不同取代度(DS)、不同MPEG相对分子质量和不同壳聚糖骨架相对分子质量的壳聚糖-g-甲氧基聚乙二醇(CS-g-MPEG)接枝共聚物,并对其结构、转化率、取代度和分子量分别采用傅里叶变换红外光谱(FT-IR)、核磁共振氢谱(1 H-NMR)和凝胶渗透色谱(GPC)进行表征,为实现纳米颗粒长循环给药及体内移植水凝胶的抗蛋白表面修饰提供材料基础。

To improve the protein repellency and long-circulation ability of chitosan as implant biomaterials and nanoparticle drug carriers in vivo, the chitosan was modified by methoxy poly （ethylene glycol） （MPEG）. To modify chitosan with MPEG, four terminal functionalization methods including terminal carboxylation, terminal aldehyde by acetic anhydride oxidation, terminal al-dehyde by catalytic oxidation and Williamson nucleophilic substitution reaction were compared. Among these methods, William-son nucleophilic substitution reaction was chosen to modify chitosan because it is a controllable synthesis method with high con-version ratio, good stability and good repeatability. The chitosan-g-MPEG （CS-g-MPEG） graft copolymers with varying degree of substitution （DS） , MPEG chain length, and chitosan molecular weight have been synthesized. The structure, conversion rati-on degree of substitution and molecular weight of the products have been characterized by Fourier transform infrared spectroscopy （FT-IR）,nuclear magnetic resonance （1H-NMR） and gel permeation chromatography （GPC）,respectively. The CS-g-MPEG graft copolymer has great potential for the drug delivery systems of long-circulation and the anti-fouling hydrogel biomaterials for transplantation in vivo.