The technology of modification of water-soluble anticancer drugs using radiation exposure

Short summary A Ukrainian University offers the technology for modifying water-soluble anticancer drugs using radiation exposure. The technology increases the effectiveness of water-soluble anticancer drugs. After conducting clinical studies, the technology will be able to use in the treatment of tumors. The university is seeking an agreement with universities and companies in the medical and pharmaceutical industries for cooperation and technical assistance to determine the properties of the technology.

Full description The experience of using antitumor chemotherapy has shown the limitations of its possibilities and low efficiency in the treatment of locally widespread and disseminated forms of malignant neoplasms. In this regard, a significant problem is the establishment of a relationship between the physical and medical-biological properties of anticancer drugs, and the modification of the pharmacological properties of already-known anticancer agents aimed at increasing efficiency and reducing toxicity. It should be noted that the modification of drug molecules with surface-active nanosized particles has important theoretical and practical significance, as it makes it possible to obtain active drugs with molecules of fixed sizes and achieve biocompatibility with body cells. The university, together with its partners, has developed the technology for modifying water-soluble pharmacological drugs to improve their therapeutic effect, which leads to the minimization of the negative consequences of the use of pharmacological drugs and the reduction of the dose of pharmacological drugs. The team from the university, in cooperation with several other Ukrainian organizations, conducted studies to determine the characteristics of the method of increasing the effectiveness of the antitumor effect of water-soluble drugs by using high-energy irradiation with electrically charged particles of saline solution (SS) before dissolving the drug in it, which led to obtaining a solution of a medicinal product, the use of which allows reducing both the amount of the medicinal product required for treatment and to minimize side effects when using it. The results of the research are illustrated by the example of the modification of the drug doxorubicin. The doxorubicin solution was prepared from doxorubicin powder. The SS irradiation was carried out with electrons with an energy of 1 MeV. The dose of radiation (DR) absorbed by the SS ranged from 4 to 80 kGy. Lewis lung carcinoma cell line (LLC) was used to study the activity of doxorubicin. The results of RF electron irradiation in the visible and ultra violet (UV) part of the spectrum are illustrated by the curves, in Fig. 1. The peculiarities of the behavior of absorption spectra (AS) of the SS were explained within the framework of the Babstone model. The influence of radiation exposure on the dependence of the AS of doxorubicin solution in non-irradiated and the irradiated the SS in infrared (IR) part of the spectrum at different DR irradiation is illustrated in Fig. 2. We see that the behavior of the AS (Fig. 2) is due to the clustering of the babstones [5-8]. In the biomedical part of in vitro research about LLC cells, the effect of doxorubicin solution using the MTT test was used as an indicator of pharmacological activity. The results of the research are illustrated in graphs Fig. 3 Similar results were obtained with the studied drugs conium and oxaliplatin. It was established that the pharmacological activity of doxorubicin is modified, the optical spectrum of doxorubicin dissolved in it changes, the minimum dose of high-energy electron irradiation absorbed by the solvent at which changes are registered is 4 kGy, the effect of high-energy electron irradiation of saline solution on the antitumor effect of doxorubicin persists for 2–4 months. The university is looking for partners to continue scientific research with the aim of: - the creation of a physical and medical portrait of oncological drugs, determination of the relationship between the physical and pharmacological characteristics of drugs, development of methods of physical identification of their therapeutic suitability; - determination of the ways of formation, properties and patterns of clustering of radiation defects in liquid media with a long lifetime; In addition, the University is looking for partners to conduct preclinical and clinical research within the framework of a commercial agreement that provides technical assistance.

Advantages and innovations 1. The study of the pharmacological activity of some antitumor drugs carried out using the Lewis lung carcinoma cell line proved that the preliminary irradiation of the FR with high-energy electrons before dissolving the drug in it leads to an increase in the cytotoxic/cytostatic effect of the drug, which is most pronounced at relatively low concentrations. 2. It was established that there is an increase in the pharmacological activity of doxorubicin, which leads to an increase in destruction, the optical spectrum of doxorubicin dissolved in it changes, the minimum dose of high-energy electron irradiation absorbed by the solvent at which changes are registered is 4 kGy, the effect of high-energy electron irradiation of saline solution on the cytostatic effect of doxorubicin stored for 2-3 months

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