环糊精聚合物的体外生物学特性:与人血清白蛋白、红细胞和细菌的相互作用

Linara R. Yakupova, Anna A. Skuredina, Tatina Yu. Kopnova, Elena V. Kudryashova
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摘要

本研究的目的是通过与人血清白蛋白、红细胞和细菌的相互作用来研究环糊精基聚合物的物理化学和生物学特性,以了解其作为药物传递系统的应用前景。以非极性(-CH3)或极性(-CH2CH(OH)CH3)取代基环糊精衍生物为基础,与1,6-六亚甲基二异氰酸酯或丁二酸酐交联,合成了聚合物。聚合物在水溶液中形成平均粒径为~200 nm的颗粒;结构经FTIR和1H NMR确证。环糊精衍生物及其聚合物不影响人血清白蛋白的二级结构含量,这可能意味着对血浆主蛋白的结构和功能特性的影响较轻。聚合物从白蛋白+药物复合物中提取药物分子的比例为8-10%,以布洛芬和溴酚蓝为模型生物活性分子对蛋白质的I和II位点进行了验证;因此,纳米颗粒可能会略微改变药物的药代动力学。通过溶血试验,我们发现聚合物与红细胞相互作用,可以作为生物相容性材料分配给非溶血和轻度溶血组,这在体内使用是安全的。环糊精及其聚合物不能从细菌细胞壁中提取蛋白质,对革兰氏阳性和革兰氏阴性菌株没有任何抗菌活性。因此,基于环糊精的聚合物具有取决于单体中的取代基和连接体类型的可变性质;具有良好的生物相容性、可生物降解性和可忽略毒性,在生物医学和生态学方面具有广阔的应用前景。
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In Vitro Biological Properties of Cyclodextrin-Based Polymers: Interaction with Human Serum Albumin, Red Blood Cells and Bacteria
The aim of this work was to investigate the physico-chemical and biological properties of cyclodextrin-based polymers by the example of interaction with human serum albumin, erythrocytes, and bacteria to understand the prospects of their application as drug delivery systems. We synthesized polymers based on one of cyclodextrin derivatives with nonpolar (-CH3) or polar (-CH2CH(OH)CH3) substituents by crosslinking with 1,6-hexamethylene diisocyanate or succinic anhydride. The polymers form particles with an average size of ~200 nm in the aqueous solutions; their structures were confirmed by FTIR and 1H NMR. Cyclodextrin derivatives and their polymers did not affect the secondary structure content of human serum albumin, which might mean a mild effect on the structural and functional properties of the main blood plasma protein. Polymers extract drug molecules from albumin + drug complex by 8–10%, which was demonstrated using ibuprofen and bromophenol blue as model bioactive molecules for site I and site II in protein; thus, the nanoparticles might slightly change the drug’s pharmacokinetics. Using the hemolysis test, we found that polymers interact with red blood cells and can be assigned to non-hemolytic and slightly hemolytic groups as biocompatible materials, which are safe for in vivo use. The cyclodextrins and their polymers did not extract proteins from bacterial cell walls and did not demonstrate any antibacterial activity against Gram-positive and Gram-negative strains. Thus, the cyclodextrin-based polymers possess variable properties depending on the substituent in the monomer and linker type; demonstrated biocompatibility, biodegradability, and negligible toxicity that opens up prospects for their application in biomedicine and ecology.
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