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

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及其用于阿霉素和紫杉醇的共输送

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

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 N-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 13C 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 N-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.

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