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用于共递送阿霉素和紫杉醇的乙烯基-2-吡咯烷酮与烯丙基缩水甘油醚两亲性共聚物的合成

Synthesis of Amphiphilic Copolymers of -Vinyl-2-pyrrolidone and Allyl Glycidyl Ether for Co-Delivery of Doxorubicin and Paclitaxel.

作者信息

Nechaeva Anna, Artyukhov Alexander, Luss Anna, Shtilman Mikhail, Gritskova Inessa, Shulgin Anton, Motyakin Mikhail, Levina Irina, Krivoborodov Efrem, Toropygin Ilya, Chistyakov Evgeniy, Gurevich Leonid, Mezhuev Yaroslav

机构信息

Department of Biomaterials, Mendeleev University of Chemical Technology of Russia, Miusskaya Sq., 9, 125047 Moscow, Russia.

Department of Chemistry and Technology of Macromolecular Compounds, MIREA-Russian Technological University (RTU MIREA), 119454 Moscow, Russia.

出版信息

Polymers (Basel). 2022 Apr 23;14(9):1727. doi: 10.3390/polym14091727.

Abstract

Co-delivery of chemotherapeutics in cancer treatment has been proven essential for overcoming multidrug resistance and improving the outcome of therapy. We report the synthesis of amphiphilic copolymers of -vinyl-2-pyrrolidone and allyl glycidyl ether of various compositions and demonstrate that they can form nanoaggregates capable of simultaneous covalent immobilization of doxorubicin by the epoxy groups in the shell and hydrophobic-driven incorporation of paclitaxel into the core of nanoparticles. The structure of the obtained copolymers was characterized by C NMR, IR, and MALDI spectroscopy, as well as adsorption at the water/toluene interface. A linear increase in the number-average molecular weight of amphiphilic copolymers and a decrease in the number-average diameter of macromolecular aggregates with an increase in the ratio -vinyl-2-pyrrolidone/allyl glycidyl ether were observed. The assembled nanocarriers were characterized by DLS. The reported novel nanocarriers can be of interest for delivery and co-delivery of a wide range of pharmacological preparations and combined therapy for cancer and other deceases.

摘要

在癌症治疗中共同递送化疗药物已被证明对于克服多药耐药性和改善治疗效果至关重要。我们报道了不同组成的N-乙烯基-2-吡咯烷酮与烯丙基缩水甘油醚两亲性共聚物的合成,并证明它们能够形成纳米聚集体,该纳米聚集体能够通过壳层中的环氧基团同时共价固定阿霉素,并通过疏水作用将紫杉醇纳入纳米颗粒的核心。通过碳核磁共振、红外光谱和基质辅助激光解吸电离质谱对所得共聚物的结构进行了表征,并对其在水/甲苯界面的吸附情况进行了研究。观察到两亲性共聚物的数均分子量随N-乙烯基-2-吡咯烷酮/烯丙基缩水甘油醚比例的增加呈线性增加,而大分子聚集体的数均直径则减小。通过动态光散射对组装的纳米载体进行了表征。所报道的新型纳米载体可能对广泛的药理制剂的递送和共同递送以及癌症和其他疾病的联合治疗具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee71/9103997/e533384d3d90/polymers-14-01727-sch001.jpg

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