New in vitro model to evaluate kinetics of antimycobacterial drug release from bioresorbable polymeric carriers

Andreevskaya SN1, Smirnova TG1, Antonov EN2, Chernousova LN1, Bogorodsky SE2, Larionova EE1, Popov VK2, Ergeshov A1
About authors

1 Laboratory of Biotechnology, Central Tuberculosis Research Institute, Moscow, Russia

2 Institute of Photon Technologies FSRC ‘Crystallography and Photonics’ RAS, Moscow, Russia

Correspondence should be addressed: Sofia N. Andreevskaya
Yauzskaya alleya, d. 2, str. 1A., Moscow, 107564; ur.liam@aifosdna

About paper

Funding: the study was supported by the Russian Ministry of Science and Higher Education and carried out as part of the State Assignment for FSRC “Crystallography and Photonics” RAS (developing an SCF-based method for creating bioactive matrices), as part of the State Assignment № 0515-2019-0015 (Formation of resistance to antimycobacterial drugs in mycobacteria and somatic cells) for the Central Tuberculosis Research Institute (evaluation of the bacteriostatic activity of different levofloxacin concentrations). The study was also supported by the Russian Foundation for Basic Research (Project № 18-29-06062 mk: development of sustained-release therapeutic formulations and an in vitro model for the evaluation of their efficacy).

Compliance with ethical standards: manipulations with virulent strains of M. tuberculosis were conducted in compliance with the safety guidelines for the experiments involving Risk Group III–IV pathogens, infectious agents and utilization of medical waste specified in sanitary regulations 1.3.2322-08, 1.3.2518-09, 1.3.2885-11, and

Author contribution: Andreevskaya SN — interpretation of study results, manuscript preparation; Smirnova TG — modeling of conditions for levofloxacin release from its carriers; discussion of study results; Antonov EN — preparation of matrices; discussion of study results; Chernousova LN, Ergeshov AE — study design; discussion of study results; Bogorodsky SE — preparation of microparticles; discussion of study results; Larionova EE — literature analysis; discussion of study results; Popov VK — method for antibiotic encapsulation into polymeric carriers; discussion of study results.

Received: 2020-08-06 Accepted: 2020-08-20 Published online: 2020-08-30

Sustained-release drugs against tuberculosis are a promising approach to therapy since they positively affect patient compliance with long regimens, especially when it comes to the multidrug-resistant form of the disease. Conventional UV-visible spectroscopy does not work well with multicomponential culture media used for growing M. tuberculosis. The aim of this study was to develop a method for evaluating the kinetics of anti-tuberculosis drug released from bioresorbable polymeric carriers suitable for screening a wide range of encapsulated prolonged-release drugs and identifying the best performing candidate. While studying the growth dynamics of the laboratory susceptible strain M. tuberculosis H37Rv in the presence of different levofloxacin concentrations (from 0.03 to 0.4 μg/ml), we developed a model, which is essentially a set of 2 parallel experiments evaluating the kinetics of drug release into the culture medium. The results of these 2 experiments conducted on 3 encapsulated forms of levofloxacin loaded onto bioresorbable polymeric PLGA carriers (particles sized 50 μm and 100 μm and the matrix) revealed that release kinetics of the drug largely depended on the type of polymeric carrier. The best encapsulation of the antibiotic and its gradual release into the culture medium was observed for the matrix. All experiments were run in 3 replicates. The obtained data were analyzed using descriptive statistics.

Keywords: Mycobacterium tuberculosis, in vitro model, levofloxacin, bioresorbable polymeric carrier, sustained-release