Kim S Y, Shin I G, Lee Y M
Department of Industrial Chemistry, College of Engineering, Hanyang University, Seoul 133-791, South Korea.
J Control Release. 1998 Dec 4;56(1-3):197-208. doi: 10.1016/s0168-3659(98)00083-2.
We synthesized amphiphilic diblock copolymer based on methoxy poly(ethylene glycol) (MePEG) and dl-lactide with different molar composition in bulk without catalyst. Using the resulting amphiphilic diblock copolymers, we prepared drug-loaded polymeric nanospheres by micelle formation through solution behavior of amphiphilic copolymer in selective solvents. The structure of MePEG/dl-lactide diblock copolymers was identified by IR, WAXD, GPC, 1H-NMR. The size of nanosphere measured by dynamic light scattering showed a narrow monodisperse size distribution and average diameter less than 200 nm. From the surface chemical composition of nanosphere by ESCA, the presence of MePEG chains on the nanosphere layers was confirmed. The critical micelle concentration of ML50 sample investigated by fluorescence spectroscopy was 1.44x10-7 mol/l which is lower than common low molecular weight surfactants. In addition, we could obtain nanospheres having a relatively high drug-loading of about 33.0% when the feed weight ratio of indomethacin to polymer was 1:1. In vitro release experiments of the indomethacin-loaded MePEG/dl-lactide nanospheres exhibited sustained release behavior without any burst effects. The results of cytotoxicity tests showed that the MePEG/dl-lactide nanospheres didn't induce any relevant cell damage.
我们在无催化剂的情况下，通过本体聚合合成了基于甲氧基聚（乙二醇）（MePEG）和外消旋丙交酯且具有不同摩尔组成的两亲性二嵌段共聚物。使用所得的两亲性二嵌段共聚物，我们通过两亲性共聚物在选择性溶剂中的溶液行为形成胶束来制备载药聚合物纳米球。通过红外光谱（IR）、广角X射线衍射（WAXD）、凝胶渗透色谱（GPC）、核磁共振氢谱（1H-NMR）对MePEG/外消旋丙交酯二嵌段共聚物的结构进行了鉴定。通过动态光散射测量的纳米球尺寸显示出窄的单分散尺寸分布，平均直径小于200nm。通过光电子能谱分析（ESCA）对纳米球的表面化学成分进行分析，证实了纳米球层上存在MePEG链。通过荧光光谱研究的ML50样品的临界胶束浓度为1.44×10-7mol/l，低于常见的低分子量表面活性剂。此外，当吲哚美辛与聚合物的进料重量比为1:1时，我们可以获得载药量相对较高约为33.0%的纳米球。载吲哚美辛的MePEG/外消旋丙交酯纳米球的体外释放实验表现出持续释放行为，没有任何突释效应。细胞毒性测试结果表明，MePEG/外消旋丙交酯纳米球不会引起任何相关的细胞损伤。
