†Laboratoire de Nanotechnologie Pharmaceutique, Faculté de Pharmacie, and ‡Canada Research Chair on Bio-inspired Materials and Interfaces Faculté de Pharmacie, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada.
ACS Appl Mater Interfaces. 2015 May 20;7(19):10374-85. doi: 10.1021/acsami.5b01423. Epub 2015 May 5.
Polymers made of poly(ethylene glycol) chains grafted to poly(lactic acid) chains (PEG-g-PLA) were used to produce stealth drug nanocarriers. A library of comblike PEG-g-PLA polymers with different PEG grafting densities was prepared in order to obtain nanocarriers with dense PEG brushes at their surface, stability in suspension, and resistance to protein adsorption. The structural properties of nanoparticles (NPs) produced from these polymers by a surfactant-free method were assessed by dynamic light scattering, ζ potential, and transmission electron microscopy and found to be controlled by the amount of PEG present in the polymers. A critical transition from a solid NP structure to a soft particle with either a "micellelike" or a "polymer nanoaggregate" structure was observed when the PEG content was between 15 and 25% w/w. This structural transition was found to have a profound impact on the size of the NPs, their surface charge, their stability in suspension in the presence of salts, and the binding of proteins to the surface of the NPs. The arrangement of the PEG-g-PLA chains at the surface of the NPs was investigated by (1)H NMR and X-ray photoelectron spectroscopy (XPS). NMR results confirmed that the PEG chains were mostly segregated at the NP surface. Moreover, XPS and quantitative NMR allowed quantification of the PEG chain coverage density at the surface of the solid NPs. Concordance of the results between the two methods was found to be remarkable. Physical-chemical properties of the NPs such as resistance to aggregation in a saline environment as well as antifouling efficacy were related to the PEG surface density and ultimately to the polymer architecture. Resistance to protein adsorption was assessed by isothermal titration calorimetry using lysozyme. The results indicate a correlation between the PEG surface coverage and level of protein interactions. The results obtained lead us to propose such PEG-g-PLA polymers for nanomedicine development as an alternative to the predominant polyester-PEG diblock polymers.
聚乙二醇（PEG）链接枝到聚乳酸（PLA）链上的聚合物（PEG-g-PLA）被用于制备隐形药物纳米载体。为了获得表面具有密集 PEG 刷的纳米载体、悬浮液稳定性和抗蛋白质吸附性，制备了一系列具有不同 PEG 接枝密度的梳状 PEG-g-PLA 聚合物库。通过无表面活性剂的方法从这些聚合物中制备纳米颗粒（NPs），通过动态光散射、ζ 电位和透射电子显微镜评估其结构性质，发现这些性质受聚合物中存在的 PEG 量的控制。当 PEG 含量在 15%至 25%w/w 之间时，观察到从固体 NP 结构到具有“胶束样”或“聚合物纳米聚集体”结构的软颗粒的临界转变。这种结构转变对 NPs 的大小、表面电荷、在盐存在下的悬浮稳定性以及蛋白质与 NPs 表面的结合有深远影响。通过（1）H NMR 和 X 射线光电子能谱（XPS）研究了 NPs 表面的 PEG-g-PLA 链的排列。NMR 结果证实 PEG 链主要在 NP 表面分离。此外，XPS 和定量 NMR 允许定量 NP 表面的 PEG 链覆盖密度。两种方法的结果之间存在显著的一致性。 NPs 的物理化学性质，如在盐环境中的抗聚集能力以及抗污能力，与 PEG 表面密度以及最终与聚合物结构有关。通过使用溶菌酶的等温滴定量热法评估了蛋白质吸附的抗性。结果表明 PEG 表面覆盖率与蛋白质相互作用的水平之间存在相关性。研究结果使我们提出将这种 PEG-g-PLA 聚合物作为纳米医学开发的替代物，用于替代主要的聚酯-PEG 嵌段聚合物。
