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胰岛素与QPDMAEMA-PLMA-POEGMA阳离子两亲性三嵌段三元共聚物胶束复合物的物理化学评估

Physicochemical Evaluation of Insulin Complexes with QPDMAEMA--PLMA--POEGMA Cationic Amphiphlic Triblock Terpolymer Micelles.

作者信息

Skandalis Athanasios, Murmiliuk Anastasiia, Štěpánek Miroslav, Pispas Stergios

机构信息

Theoretical and Physical Chemistry Institute, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 11635 Athens, Greece.

Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, Hlavova 2030, 128 40 Prague 2, Czech Republic.

出版信息

Polymers (Basel). 2020 Feb 3;12(2):309. doi: 10.3390/polym12020309.

Abstract

Herein, poly[quaternized 2-(dimethylamino)ethyl methacrylate--lauryl methacrylate--(oligo ethylene glycol)methacrylate] (QPDMAEMA--PLMA--POEGMA) cationic amphiphilic triblock terpolymers were used as vehicles for the complexation/encapsulation of insulin (INS). The terpolymers self-assemble in spherical micelles with PLMA cores and mixed QPDMAEMA/POEGMA coronas in aqueous solutions. The cationic micelles were complexed via electrostatic interactions with INS, which contains anionic charges at pH 7. The solutions were colloidally stable in all INS ratios used. Light-scattering techniques were used for investigation of the complexation ability and the size and surface charge of the terpolymer/INS complexes. The results showed that the size of the complexes increases as INS ratio increases, while at the same time the surface charge remains positive, indicating the formation of clusters of micelles/INS complexes in the solution. Fluorescence spectroscopy measurements revealed that the conformation of the protein is not affected after the complexation with the terpolymer micellar aggregates. It was observed that as the solution ionic strength increases, the size of the QPDMAEMA--PLMA--POEGMA/INS complexes initially decreases and then remains practically constant at higher ionic strength, indicating further aggregation of the complexes. atomic force microscopy (AFM) measurements showed the existence of both clusters and isolated nanoparticulate terpolymer/protein complexes.

摘要

在此,聚季铵化甲基丙烯酸2-(二甲氨基)乙酯-甲基丙烯酸月桂酯-(聚乙二醇)甲基丙烯酸酯阳离子两亲性三嵌段三元共聚物被用作胰岛素(INS)络合/包封的载体。这些三元共聚物在水溶液中自组装成具有PLMA核和混合QPDMAEMA/POEGMA冠层的球形胶束。阳离子胶束通过与在pH 7时带负电荷的INS发生静电相互作用而络合。在所有使用的INS比例下,溶液在胶体状态下都是稳定的。采用光散射技术研究三元共聚物/INS络合物的络合能力、尺寸和表面电荷。结果表明,随着INS比例的增加,络合物的尺寸增大,而同时表面电荷仍为正,这表明在溶液中形成了胶束/INS络合物簇。荧光光谱测量表明,蛋白质与三元共聚物胶束聚集体络合后其构象不受影响。观察到随着溶液离子强度的增加,QPDMAEMA-PLMA-POEGMA/INS络合物的尺寸最初减小,然后在较高离子强度下基本保持不变,这表明络合物发生了进一步聚集。原子力显微镜(AFM)测量显示存在簇和孤立的纳米颗粒状三元共聚物/蛋白质络合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ec0/7077422/e26eae3e2c7d/polymers-12-00309-g006.jpg

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