ИСТИНА

Проект направлен на снижение токсичности таких лекарственных препаратов как кортикостероиды и винкристин с сохранением их высокой эффективности для терапии аутоиммунных и противоопухолевых заболеваний путем создания их пролонгированных форм на основе эритроцитов как переносчиков.

The project aims to reduce the toxicity of drugs such as corticosteroids and vincristine while preserving their high effectiveness in the treatment of autoimmune and antitumor diseases by creating their prolonged forms based on erythrocytes as carriers. Despite their high effectiveness, the use of both types of drugs is limited by their toxicity, especially during long-term use, which is relevant for conditions such as rheumatoid arthritis, psoriasis, lupus, autoimmune hemolytic anemia in the case of corticosteroids, and various types of cancer in the case of vincristine. Encapsulation of these drugs in erythrocytes will allow the creation of a depot form with gradual slow release into the bloodstream at a dose sufficient for therapy without high peak concentrations at the time of administration. This prolongs the action of the drug and reduces its toxic effects caused by high peak concentration in the bloodstream. Encapsulation of drugs in erythrocytes has proven to be effective, and numerous studies demonstrate the advantages of this delivery form, including complete biocompatibility of the drug carrier, prolonged therapeutic effect along with reduced drug toxicity, and ease of obtaining such carriers for delivery. This procedure requires a small volume of autologous or donor erythrocytes isolated from 100-200 ml of whole blood. Corticosteroids (dexamethasone, prednisolone) are cornerstone drugs for the treatment of autoimmune hemolytic anemia and are part of the supportive therapy for many other common diseases (rheumatoid arthritis, psoriasis, ulcerative colitis, etc.). The effectiveness and response to corticosteroid therapy depend on the duration of treatment and the dose of these drugs; however, prolonged therapy is accompanied by serious side effects that compete with the primary disease. Therefore, reducing the side effects of corticosteroids while maintaining their effectiveness is a current challenge. Vincristine is a chemotherapeutic drug used to treat various types of cancer, including leukemia, lymphoma, neuroblastoma, Wilms tumor, central nervous system (CNS) tumors, Young's sarcoma, gestational trophoblastic tumors, etc. Vincristine has played a key role in treating acute lymphoblastic leukemia (ALL) in children since its introduction in 1962. The concentration of vincristine that affects cells is an important factor determining its anti-leukemic effect. However, its dose is limited by its toxicity. The most common and dose-limiting toxicity associated with vincristine is neurotoxicity, which can affect the peripheral, central, and autonomic nervous systems. Slow release of vincristine from erythrocytes will reduce the high peak load of the drug compared to standard administration, which will firstly reduce toxicity and secondly allow for a higher dose when necessary but currently unavailable due to dose-limiting toxicity. This increase in the therapeutic index due to reduced toxicity is a valuable distinction between standard and erythrocyte forms of drug administration.

В ожидаемые результаты входит создание эритроцитов-переносчиков кортикостероидов и винкристина с их постепенным высвобождением в кровоток, что будет способствовать снижению высокой токсичности данных препаратов, конкурирующей с основным заболеванием. Значимость создания пролонгированных форм кортикостероидов и викристина обусловлена их широким применением и высокой эффективностью при различных заболеваниях наряду с токсичностью.