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Kulikova VV, Morozova EA, Anufrieva NV, et al. Kinetic and pharmacokinetic characteristics of therapeutic methinoninе γ-lyase encapsulated in polyion complex vesicles. Biochimie. 2021;doi: 10.1016/j.biochi.2021.12.004.
Kulikova, V. V., Morozova, E. A., Anufrieva, N. V., Koval, V. S., Lyfenko, A. D., Lesnova, E. I., Kushch, A. A., Revtovich, S. V., & Demidkina, T. V. (2021). Kinetic and pharmacokinetic characteristics of therapeutic methinoninе γ-lyase encapsulated in polyion complex vesicles. Biochimie, . https://doi.org/10.1016/j.biochi.2021.12.004
Kulikova, Vitalia V, et al. "Kinetic and pharmacokinetic characteristics of therapeutic methinoninе γ-lyase encapsulated in polyion complex vesicles." Biochimie vol. (2021). doi: https://doi.org/10.1016/j.biochi.2021.12.004
Kulikova VV, Morozova EA, Anufrieva NV, Koval VS, Lyfenko AD, Lesnova EI, Kushch AA, Revtovich SV, Demidkina TV. Kinetic and pharmacokinetic characteristics of therapeutic methinoninе γ-lyase encapsulated in polyion complex vesicles. Biochimie. 2021 Dec 16; doi: 10.1016/j.biochi.2021.12.004. Epub 2021 Dec 16. PMID: 34923045.
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Biochimie. 2021 Dec 16; doi: 10.1016/j.biochi.2021.12.004. Epub 2021 Dec 16.

Kinetic and pharmacokinetic characteristics of therapeutic methinoninе γ-lyase encapsulated in polyion complex vesicles.

Biochimie

Vitalia V Kulikova, Elena A Morozova, Natalya V Anufrieva, Vasiliy S Koval, Anna D Lyfenko, Ekaterina I Lesnova, Alla A Kushch, Svetlana V Revtovich, Tatyana V Demidkina

Affiliations

  1. Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, Vavilov street, 32, Moscow, 119991, Russia. Electronic address: [email protected].
  2. Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, Vavilov street, 32, Moscow, 119991, Russia.
  3. Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, 123098, Russia.

PMID: 34923045 DOI: 10.1016/j.biochi.2021.12.004

Abstract

Therapeutic enzymes used for the treatment of a wide range of human disorders often suffer from suboptimal pharmacokinetics and stability. Engineering approaches such as encapsulation in micro- and nanocarriers, and replacements of amino acid residues of the native enzyme provide significant potential for improving the performance of enzyme therapy. Here, we develop a nanodelivery system on the base of polyion complex vesicles (PICsomes) that includes methionine γ-lyase (MGL) as a therapeutic enzyme. We have two strategies for using the enzyme: first, methionine γ-lyase is an anticancer agent removing l-methionine from plasma, second, the binary system methionine γ-lyase/S-alk(en)yl-l-cysteine sulfoxides is effective in enzyme prodrug therapy (EPT). Various lengths polymers were synthesized, and two mutant forms of the enzyme were used. The catalytic and pharmacokinetic parameters of the nanoformulations were investigated. The catalytic efficiencies of encapsulated enzymes were comparable to that of native enzymes. Pharmacokinetic analysis has shown that inclusion into PICsomes increases half-life of the enzymes, and they can be safely administered in vivo. The results suggest the further use of encapsulated MGLs for EPT and anticancer therapy, and this strategy could be leveraged to improve the efficiency of enzyme-based therapies for managing serious human diseases.

Copyright © 2021. Published by Elsevier B.V.

Keywords: Anticancer therapy; Enzyme prodrug therapy; Kinetics; Methionine γ-lyase; PICsomes; Pharmacokinetics

Conflict of interest statement

Declaration of competing interest We have no conflict of interest to declare.

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