| Autor: |
Karpov TE; Peter The Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, St. Petersburg 195251, Russian Federation. karpov_te@spbstu.ru., Rogova A; Peter The Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, St. Petersburg 195251, Russian Federation. karpov_te@spbstu.ru., Akhmetova DR; Peter The Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, St. Petersburg 195251, Russian Federation. karpov_te@spbstu.ru.; ITMO University, Lomonosova 9, St. Petersburg 191002, Russian Federation. shipilovskikh@itmo.ru., Tishchenko YA; Peter The Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, St. Petersburg 195251, Russian Federation. karpov_te@spbstu.ru.; Alferov Saint Petersburg National Research Academic University, Khlopin Street 8/3A, St. Petersburg 194021, Russian Federation., Chinakova AV; Alferov Saint Petersburg National Research Academic University, Khlopin Street 8/3A, St. Petersburg 194021, Russian Federation., Lipin DV; ITMO University, Lomonosova 9, St. Petersburg 191002, Russian Federation. shipilovskikh@itmo.ru., Gavrilova NV; Peter The Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, St. Petersburg 195251, Russian Federation. karpov_te@spbstu.ru.; Smorodintsev Research Institute of Influenza, Ministry of Healthcare of the Russian Federation, Prof. Popov Str. 15/17, St. Petersburg 197376, Russian Federation., Gorbunova IA; ITMO University, Lomonosova 9, St. Petersburg 191002, Russian Federation. shipilovskikh@itmo.ru., Shipilovskikh SA; ITMO University, Lomonosova 9, St. Petersburg 191002, Russian Federation. shipilovskikh@itmo.ru.; Perm State University, Bukireva 15, Perm, 614990, Russian Federation., Timin AS; Peter The Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, St. Petersburg 195251, Russian Federation. karpov_te@spbstu.ru. |
| Abstrakt: |
Although small molecule drugs are widely used in chemotherapy, their low bioavailability, low-concentrated dose in the tumor zone, systemic toxicity, and chemoresistance can significantly limit the therapeutic outcome. These drawbacks can be overcome by two main strategies: (i) development of novel therapeutic molecules with more significant antitumor activity than currently available drugs and (ii) loading chemotherapeutic agents into drug delivery systems. In this study, we aimed to encapsulate a highly prospective small molecule drug based on substituted 2-aminothiophene (2-AT) into calcium carbonate (CaCO 3 ) microparticles (MPs) for the treatment of melanoma tumors. In particular, we have optimized the encapsulation of 2-AT into MPs (2-AT@MPs), studied drug release efficiency, investigated cellular uptake, and evaluated in vivo biodistribution and tumor inhibition efficiency. In vitro results revealed that 2-AT@MPs were able to penetrate into tumor spheroids, leading to prolonged release of 2-AT. By performing intratumoral injection of 2-AT@MPs we observed significant melanoma suppressions in murine models: ∼0.084 cm 3 for 2-AT@MPs at a dose of 0.4 g kg -1 versus ∼1.370 cm 3 for untreated mice. In addition, the 2-AT@MPs showed negligible in vivo toxicity towards major organs such as heart, lung, liver, kidney, and spleen. Thus, this work provided an efficient strategy for the improved chemotherapy of solid tumors by using an encapsulated form of small molecule drugs. |
