STUDY OF LIPOSOME ENCAPSULATED MONOACETATE GLYCOLYSIS INHIBITOR AS AN ANTITUMOR AGENT IN A LEWIS LUNG CARCINOMA MODEL

DOI: https://doi.org/10.29296/25877313-2020-06-08
Issue: 
6
Year: 
2020

E.E. Buyko Post-graduate Student, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University (Tomsk) Е-mail: buykoevgen@yandex.ru D.A. Korshunov Ph.D. (Med.), Research Scientist, Laboratory of Tumor Biochemistry, Cancer Research Institute, Tomsk National Research Medical Center (Tomsk) Е-mail: ieved@ya.ru I.V. Kondakova Dr.Sc. (Med.), Head of Laboratory of Tumor Biochemistry, Cancer Research Institute of National Research Medical Center (Tomsk) Е-mail: kondakova@oncology.tomsk.ru

Background. Advances in understanding the molecular mechanisms associated with the Warburg effect have become the basis for the creation of new specific anti-glycolytic agents. Despite their successful preclinical trials, many new anticancer agents based on glycolysis inhibitors have failed in clinical trials, demonstrating systemic toxicity. An effective approach to reducing systemic intoxication is targeted drug delivery using liposomes. However, there are technical difficulties in obtaining liposomes for low molecular weight compounds, which include glycolysis inhibitors, as well as the efficiency of delivery to the tumor due to the peculiarities of liposome bio-distribution and pharmacokinetics. Aims. To evaluate the antitumor and antimetastatic effects of a monoiodoacetate glycolysis inhibitor immersed in liposomes. Material and methods. The therapeutic effect of antimetabolite was evaluated in C57BL/6j mice using a Lewis lung carcinoma model. Methotrexate was used as a reference preparation. Liposomes were obtained by extrusion. Ready liposomes were purified from the not included component by dial-ysis methods. Liposomes were injected through the tail vein. Results. The inhibition of the growth of the primary tumor in iodoacetate in an independent form was comparable with the effect of methotrexate, reaching an average of 15%. Treating with liposomal forms of iodoacetate increased the growth inhibition index to 25%. Inhibition of the growth of lung metastases in iodoacetate and methotrexate was stronger than the effect of drugs on the primary tumor. The averages in these treated groups were 65%. The liposomal form of iodoacetate, in contrast to the similar form of methotrexate, did not significantly inhibit the growth of metastases. Conclusions. Liposomal forms of iodoacetate inhibit the growth of the primary focus more strongly in comparison with their independent action, how-ever, as a result of changes in biodistribution, the antimetastatic effect decreases.

Keywords: 
iodoacetate
methotrexate
liposomal dosage forms
antitumor effect

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