摘要
背景:多糖引入疏水基团后,在水中能自组装成胶束,可作为疏水小分子药物及生物活性大分子(多肽、蛋白和基因)的载体,在医药和生物技术领域有着潜在的应用价值。目的:系统考察胆固醇基取代度和普鲁兰多糖相对分子质量对改性普鲁兰纳米粒子性状的影响。方法:将胆固醇修饰到不同相对分子质量的普鲁兰多糖长链上,合成了一系列取代度不同的胆固醇基-普鲁兰改性多糖,使其在水中自组装成纳米粒子,考察胆固醇取代度及多糖相对分子质量对纳米粒子形态的影响,以阿霉素为模型药物,研究了其在胆固醇基-普鲁兰改性多糖纳米粒子中的包封及体外释放行为。结果与结论:随着相对分子质量和取代度的增加,粒子稳定性增强,临界胶束质量浓度降低。胆固醇基取代度越低、多糖相对分子质量越大,载药量和包封率越高;当取代度和相对分子质量相同时,随着投料比的增加,载药量增加而包封率降低。体外释放结果表明,相对分子质量越大,粒子越稳定,载药量越高,药物释放越慢。
BACKGROUND：Hydrophobically modified polysaccharides can self-assemble into micelle in water,are used as a carrier of hydrophobic micromolecule drugs and bioactive macromolecules （polypeptide,protein and gene）,and have potential application values in biotechnology and medicine.OBJECTIVE：To comprehensively investigate the influence of cholesterol-based degree of substitution and relative molecular weight of pullulan polysaccharides on the properties of modified pullulan nanoparticles.METHODS：Various cholesterol-bearing pullulans with different molecular weights of parent pullulan and degrees of substitution of cholesteryl moiety were synthesized.The resulting cholesteryl-pullulan modified polysaccharides were self-assembled in water into nanoparticles.The influence of cholesterol-based degree of substitution and relative molecular weight of polysaccharides on the properties of nanoparticles was observed.With doxorubicin as model drug,the encapsulating and in vitro release behavior on cholesteryl-pullulan modified polysaccharide nanoparticles were investigated.RESULTS AND CONCLUSION：With the degree of substitution and molecular weights increased,the stability of the nanoparticles enhanced,critical micelle concentration decreased.Loading capacity and encapsulation efficiency of the nanoparticles increased with increasing of molecular weights of the parent pullulan and decreasing of cholesterol degree of substitution in the same feed ratio.Higher feed ratio could lead to higher loading capacity and lower encapsulation efficiency under the same degree of substitution of cholesteryl moiety and molecular weights of parent pullulan.Drug showed slower release in vitro from the nanoparticles with higher molecular weights of parent pullulan,higher stability of the nanoparticles,and higher drug contents.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2010年第38期7119-7123,共5页
Journal of Clinical Rehabilitative Tissue Engineering Research
基金
国家重大科学研究计划项目(2006CB933300)
博士点基金(20091106120051)~~
