Synthesis of a fructose decorated PAGE-b-PEG-b-PLGA polymer with subsequent formulation of nanoparticles
Synthesis of a fructose decorated PAGE-b-PEG-b-PLGA polymer with subsequent formulation of nanoparticles
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DOI：
10.1016/j.colsurfa.2020.124701
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发表时间：
2020-07
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通讯作者：
J. Czaplewska;G. Gangapurwala;A. Vollrath;Michael Pröhl;Tobias C. Majdanski;D. Pretzel;S. Hoeppener;U. Schubert;M. Gottschaldt
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作者：
J. Czaplewska;G. Gangapurwala;A. Vollrath;Michael Pröhl;Tobias C. Majdanski;D. Pretzel;S. Hoeppener;U. Schubert;M. Gottschaldt
在此，我们提出了基于药物相关共聚物的 D-果糖修饰纳米颗粒 (NP)，该共聚物由聚乙二醇 (PEG) 和聚丙交酯乙交酯共聚物 (PLGA) 以及额外的烯丙基缩水甘油醚 (PAGE) 嵌段组成。 PAGE-b-PEG-b-PLGA 聚合物通过开环聚合合成，并通过硫代-D-果糖单元和 PAGE 单元双键之间所谓的硫醇-烯“点击”反应实现后官能化。果糖修饰聚合物以及对照聚合物 mPEG-b-PLGA 通过尺寸排阻色谱 (SEC) 和核磁共振波谱 (NMR) 进行了全面表征。随后，它们被用于 NP 配方维亚诺沉淀，从而与荧光标记的 PLGA 进行复合配方，以实现颗粒的可见性。通过动态光散射 (DLS) 和扫描电子显微镜 (SEM) 研究证实，获得了流体动力学直径为 100 nm 且 PDI 值较低（0.11 至 0.25）的纳米颗粒。在配方中使用0.3%（w/v）部分水解的聚（乙烯醇）溶液显着提高了纳米粒子在不同纯化和储存过程（例如离心和冷冻干燥）中的稳定性。在醋酸盐缓冲液 (pH 4.9) 和 PBS (pH 7.4) 以及人工溶酶体液 (pH 4.5 和 7.4) 中进一步检查了 NP 稳定性。 NP 在所有介质中至少 48 小时内均表现出良好的稳定性。最后，测试了纳米颗粒在不同细胞系（MDA-MB-231、HEK-293）中的细胞毒性，未观察到颗粒对细胞的有害影响。
Herein we presentD-fructose decorated nanoparticles (NPs) based on a pharmarelevant copolymer consisting of poly(ethyleneglycol) (PEG) and poly(lactide-co-glycolide) (PLGA) with an additional allyl glycidyl ether (PAGE) block. The PAGE-b-PEG-b-PLGA polymer was synthesizedviaring-opening polymerization and enables post-functionalizationviathe so-called thiol-ene ‘click’ reaction between thio-D-fructose units and the double bond of the PAGE units. The fructose decorated polymer as well as the control polymer mPEG-b-PLGA were fully characterized by size exclusion chromatography (SEC) and nuclear magnetic resonance spectroscopy (NMR). Subsequently, they were used for NP formulationviananoprecipitation, whereby a co-formulation with a fluorescently labeled PLGA was performed to enable visibility of the particles. NPs with a hydrodynamic diameter of 100 nm with low PDI values (0.11 to 0.25) were obtained as confirmed by dynamic light scattering (DLS) and scanning electron microscopy (SEM) studies. The utilization of a 0.3% (w/v) partially hydrolyzed-poly(vinyl alcohol) solution in the formulation significantly improved the stability of the NPs during different purification and storage processes, such as centrifugation and freeze-drying. The NP stability was further examined in acetate buffer (pH 4.9) and PBS (pH 7.4) as well as in artificial lysosomal fluids (pH 4.5 and 7.4). The NPs showed good stability in all media for at least 48 h. Finally, the NPs were tested for their cytotoxicity in different cell lines (MDA-MB-231, HEK-293) whereby no harmful effects of the particles on the cells could be observed.