多糖分子质量与配基连接臂长度对改性普鲁兰药物载体的性质影响

Influence of molecular weight and spacer length on the properties of modified pullulan carriers

目的 研究普鲁兰分子质量和胆固醇配基连接臂长度对胆固醇改性普鲁兰自组装、载药及体外释放等性质的影响.方法 将胆固醇通过2种长度的连接臂共价修饰到2种分子质量的普鲁兰多糖上,合成不同取代度的胆固醇改性普鲁兰（共8种）,使其在水中组装成纳米粒,并考察多糖分子质量及连接臂长度对纳米粒形态、粒径的影响.同时,以阿霉素、米托蒽醌为模型药物,考察其在改性普鲁兰多糖纳米粒中的包封及释放行为特征.结果 所有改性普鲁兰多糖均可形成纳米粒,包封药物后可形成载药纳米粒;多糖分子质量和连接臂长度对其性质具有一定的影响.结论 载药前,分子质量较大、连接臂较短的改性多糖具有更好的稳定性;载药后,其对药物的包封、粒径、体外释放行为的影响规律与药物种类相关.

Objective To investigate the influence of pullulan molecular weight and spacer length on the properties of modified pullulan carriers including morphologies,sizes and in vitro release behaviours of drug-loading carriers.Methods Using cholesterol as hydrophobic ligand,succinic anhydride and 1,6-hexyldiisocyanate as spacers,hydrophobic modified pullulans with different molecular weights were prepared.Self-assembled nanoparticles were then formed in the aqueous solution,and drug-loaded nanoparticles were prepared by dialysis method.The influence of pullulan molecular weight and spacer length on the loading-content,morphologies and in vitro release behaviours of drug-loading nanoparticles were then investigated in detail.Results Self-assembled nanoparticles could be formed by the cholesterol-modified pullulan,and doxorubicin and mitoxantrone could be loaded into cholesterol-modified pullulan to form nanoparticles.Pullulan molecular weight and spacer length show influences on sizes,morphologies and stabilities of pullulan nanoparticles and drug-loaded nanocarriers.Conclusions Before drug loading,nanoparticles with larger moleculare weight and shorter spacer length are more stable in solution,while after drug loading,the influences of these two factors on the nanoparticles are drug-type depended.