Artyukhov Alexander A, Nechaeva Anna M, Shtilman Mikhail I, Chistyakov Evgeniy M, Svistunova Alina Yu, Bagrov Dmitry V, Kuskov Andrey N, Docea Anca O, Tsatsakis Aristides M, Gurevich Leonid, Mezhuev Yaroslav O
Department of Biomaterials, Mendeleev University of Chemical Technology of Russia, 125047 Moscow, Russia.
Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia.
Materials (Basel). 2022 Oct 13;15(20):7136. doi: 10.3390/ma15207136.
Application of nanocarriers for drug delivery brings numerous advantages, allowing both minimization of side effects common in systemic drug delivery and improvement in targeting, which has made it the focal point of nanoscience for a number of years. While most of the studies are focused on encapsulation of hydrophobic drugs, delivery of hydrophilic compounds is typically performed via covalent attachment, which often requires chemical modification of the drug and limits the release kinetics. In this paper, we report synthesis of biphilic copolymers of various compositions capable of self-assembly in water with the formation of nanoparticles and suitable for ionic binding of the common anticancer drug doxorubicin. The copolymers are synthesized by radical copolymerization of N-vinyl-2-pyrrolidone and acrylic acid using n-octadecyl-mercaptan as a chain transfer agent. With an increase of the carboxyl group's share in the chain, the role of the electrostatic stabilization factor of the nanoparticles increased as well as the ability of doxorubicin as an ion binder. A mathematical description of the kinetics of doxorubicin binding and release is given and thermodynamic functions for the equilibrium ionic binding of doxorubicin are calculated.
纳米载体在药物递送中的应用带来了诸多优势,既能将全身给药中常见的副作用降至最低,又能改善靶向性,这使得它多年来一直是纳米科学的焦点。虽然大多数研究集中在疏水性药物的包封上,但亲水性化合物的递送通常通过共价连接来进行,这往往需要对药物进行化学修饰,并限制了释放动力学。在本文中,我们报道了合成各种组成的双亲性共聚物,这些共聚物能够在水中自组装形成纳米颗粒,并适用于常见抗癌药物阿霉素的离子结合。这些共聚物是通过N-乙烯基-2-吡咯烷酮和丙烯酸的自由基共聚反应,以正十八烷基硫醇作为链转移剂合成的。随着链中羧基份额的增加,纳米颗粒的静电稳定因子的作用以及阿霉素作为离子结合剂的能力也随之增加。给出了阿霉素结合和释放动力学的数学描述,并计算了阿霉素平衡离子结合的热力学函数。