Max Mousseron Institute on Biomolecules, UMR CNRS 5247, Faculty of Pharmacy, University Montpellier I, 34060 Montpellier, France.
Int J Pharm. 2010 Jul 15;394(1-2):43-9. doi: 10.1016/j.ijpharm.2010.04.030. Epub 2010 Apr 29.
A series of diblock copolymers were synthesized by ring-opening polymerization of l- or d-lactide in the presence of monomethoxy poly(ethylene glycol) (mPEG) with molar masses of 2000 and 5000. The aggregation behavior of the resulting water soluble PLA/PEG diblock copolymers in aqueous medium was studied with dynamic and static light scattering (DLS and SLS), in combination with aqueous gel permeation chromatography (GPC). The average hydrodynamic radius (R(h)) of l-PLA/PEG and d-PLA/PEG mixed micelles is lower than that of l-PLA/PEG single micelles due to the stereocomplexation effect between l-PLA and d-PLA blocks. It is also confirmed that the micelle size increases with increasing temperature and hydrophobic block length, but decreases after salt addition. Aqueous GPC and SLS were used to evaluate the molecular weight (M(w)) and aggregation number (N(agg)) of the micelles. Mixed micelles present lower N(agg) than single copolymer micelles due to stereocomplexation. N(agg) decreases with increasing hydrophobic block length, and decreases upon addition of NaCl, in agreement with a more compact structure. In contrast, N(agg) increases with elevating temperature. The average radius of gyration (R(g)) and R(g)/R(h) ratio data show that both increase with increasing temperature, suggesting that micelles exhibit a compact hard-sphere structure at 15 degrees C and a swollen structure at 35 degrees C. As the temperature increases from 15 degrees C to 35 degrees C, the second virial coefficient (A(2)) of PLA/PEG copolymers turns from negative to positive, which means that water changes from poor solvent to good solvent. The fact that the average density (rho) of PLA/PEG micelles decreases with increasing temperature confirms that micelles exhibit a looser structure at higher temperatures due to water swelling effect. The higher rho value of mixed micelles as compared to single micelles also confirms a more compact structure of the former. In addition, due to the much higher N(agg) and lower R(h), PLA/PEG2000 micelles present higher rho value than PLA/PEG5000 ones.
一系列的嵌段共聚物通过在 2000 和 5000 的单甲氧基聚乙二醇（mPEG）存在下的开环聚合 l-或 d-丙交酯合成。在水溶液中，使用动态和静态光散射（DLS 和 SLS）与水凝胶渗透色谱（GPC）相结合来研究所得水溶性 PLA/PEG 嵌段共聚物的聚集行为。由于 l-PLA 和 d-PLA 嵌段之间的立体复合物效应，l-PLA/PEG 和 d-PLA/PEG 混合胶束的平均水动力半径（R（h））低于 l-PLA/PEG 单胶束。还证实，随着温度和疏水性嵌段长度的增加，胶束尺寸增加，但加盐后减小。水凝胶渗透色谱和 SLS 用于评估胶束的分子量（M（w））和聚集数（N（agg））。由于立体复合物化，混合胶束的 N（agg）低于单共聚物胶束。N（agg）随疏水性嵌段长度的增加而减小，并且在添加 NaCl 时减小，这与更紧凑的结构一致。相反，N（agg）随温度升高而增加。平均回转半径（R（g））和 R（g）/R（h）比值数据表明，两者都随温度升高而增加，这表明胶束在 15 摄氏度下表现出紧凑的硬球结构，在 35 摄氏度下表现出肿胀结构。当温度从 15 摄氏度升高到 35 摄氏度时，PLA/PEG 共聚物的第二维里系数（A（2））从负变为正，这意味着水从不良溶剂变为良溶剂。PLA/PEG 胶束的平均密度（rho）随温度升高而降低的事实证实，由于水膨胀效应，胶束在较高温度下表现出较松散的结构。与单胶束相比，混合胶束的较高 rho 值也证实了前者的更紧凑的结构。此外，由于更高的 N（agg）和更低的 R（h），PLA/PEG2000 胶束的 rho 值高于 PLA/PEG5000 胶束。
