Study of interaction of terpeno-indole alkaloids with blood components by the gel filtration method
Abstract
The problems of directional transport of drugs in the body, which make it possible to maximize the effectiveness of therapy and reduce systemic toxic side reactions, are becoming increasingly important. In the literature, there is evidence of the possibility of using cellular carriers as delivery systems for various drugs to pathologically altered organs and target cells. In connection with this, it is important to study the possibility of using cellular carriers to load highly toxic antitumoral alkaloids of the indole group that are part of the standards for the treatment of certain oncological diseases - vincristine and vinblastine, in order to reduce side effects, improve the effectiveness of the drug, and tolerate chemotherapy. To solve this problem, it is necessary to study the pharmacokinetic characteristics of the interaction of these drugs with plasma and cellular elements of blood to develop a rational technique for encapsulating these drugs in erythrocytes.
To obtain the erythrocyte cell form of the studied substances, a modified method of hypoosmotic lysis was used. Isolation of alkaloids from the biological material was carried out by the gel filtration method. It has been established that the preparations of terpene-indole alkaloids have a high ability to bind to plasma components and shaped elements of blood. With components of the plasma binding is carried out for vincristine at 52.67%, and for vinblastine - 53.04% of the total binding amount of preparations of alkaloids. In the experiment, it was found that the interaction of vincristine with the shaped elements of blood (erythrocytes) is 46.91%, and vinblastine - 46.23% of the administered dose. In accordance with the obtained experimental data, it is possible to determine the optimal conditions for encapsulating these preparations in erythrocytes to create cellular carriers and to carry out directed transport of these drugs in the body.
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