1H-NMR法测定单甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物纳米粒的表面单甲氧基聚乙二醇含量及链密度  

The Study of MePEG Content and Chain Density on MePEG-PLGA-NP Surface with 1 H-NMR Method

作　　者：王俊腾[1] 谢鑫鑫[1] 秦利芳[1] 林东海[1] 

机构地区：[1]烟台大学药学院药剂教研室,山东烟台264005

出　　处：《中国药学杂志》2012年第16期1302-1307,共6页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(30973949);山东省自然科学基金资助项目(ZR2009CM012)

摘　　要：目的采用1H-NMR定量地测定单甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物纳米粒(MePEG-PLGA-NP)表面单甲氧基聚乙二醇(MePEG)的含量及链密度,并研究了不同相对分子质量及不同比例的单甲氧基聚乙二醇对单甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物纳米粒表面的物理化学性质影响。方法以单甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物(MePEG-PLGA)为载体,自乳化溶剂扩散法制备了聚乙二醇化聚乳酸-羟基乙酸纳米粒,并对其平均粒径和Zeta电位进行表征。1H-NMR用于确定单甲氧基聚乙二醇-聚乳酸-羟基乙酸的结构组成并测定了单甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物纳米粒表面的单甲氧基聚乙二醇的含量及链密度,并与比色法进行比较。结果单甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物共聚物的结构组成与标示量基本一致;聚乙二醇的相对分子质量相同时,随着单甲氧基聚乙二醇比例的增加,单甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物纳米粒的平均粒径逐渐减小,Zeta电位的绝对值也逐渐减小,粒子表面的单甲氧基聚乙二醇含量(α)逐渐增加,其表面单甲氧基聚乙二醇的链密度(δ)逐渐增大,相邻两单甲氧基聚乙二醇分子链间的距离(D)逐渐减小;相同比例,随着单甲氧基聚乙二醇链长度的增加,单甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物纳米粒的平均粒径与Zeta电位都无明显差别,而α逐渐增加,δ逐渐减小,D逐渐增大;同种单甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物纳米粒,比色法测定的α值比1H-NMR测定的值偏高。结论1H-NMR能够定量地测定单甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物纳米粒表面的单甲氧基聚乙二醇含量及链密度;与比色法相比,1H-NMR测定的粒子表面单甲氧基聚乙二醇的含量更准确;实验范围内,单甲氧基聚乙二醇的相对分子质量和比例可以对纳米粒的平均粒径,Zeta电位和表面单OBJECTIVE 1H-NMR （ Nuclear Magnetic Resonance Method） was used to quantitatively determine the MePEG （ methoxy polyethylene glycol） content and chain density on MePEG-PLGA-NP surface, and study the influences of MePEG molecular weights and proportion on the chemical and physical properties of MePEG-PLGA-NP surface. METHODS MePEG-PLGA-NP were prepared by self-emulsion solvent diffusion method with methoxy polyethylene glycol - poly（ lactic acid-hydroxyl acid） copolymer （ MePEG-PLGA） as the carriers . And the particle average size and Zeta potential were characterized. 1H-NMR method were used to ascer- tain the composition of the MePEG-PLGA copolymer and determine the MePEG content and chain density on the MePEG-PLGA-NP sur- face , and compared with colorimetric assay. RESULTS The composition of MePEG-PLGA copolymer are basically the same with the labelled amount. When the Molecular weight is at the same, along with the increase of proportion of MePEG, the average size of Me- PEG-PLGA-NP decrease, the absolute value of the Zeta potential also decrease gradually, MePEG content on particles surface （α） in- crease gradually, the MePEG chain density on nanoparticles surface （8） increase gradually, the distance between two adjacent MePEG chains on the surface of the particles （D） decrease ; When there is the same proportions, with MePEG chain length increases, nanop- articles are not significantly different on the particle average size and the Zeta potential, whereas α increase gradually, the 8 decreases, and D increases ; Thectvalue of the same MePEG-PLGA-NP determined by colorimetric assay is higher than which is determined by 1H- NMR. CONCLUSION 1H-NMR method can be used to quantitatively determine the MePEG content and chain density on MePEG- PLGA-NP surface; Compared with the traditional method, the results determined by 1H-NMR method are more accurate. With the experimental limits, MePEG molecular weighs and proportion have influences on the chemical and physical properties of MePEG-P

关 键 词：聚乳酸-羟基乙酸共聚物 单甲氧基聚乙二醇 纳米粒 核磁共振法 链密度 

分 类 号：R944[医药卫生—药剂学]