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. 2022 Jun 15;14(6):1275.
doi: 10.3390/pharmaceutics14061275.

PLGA Carriers for Controlled Release of Levofloxacin in Anti-Tuberculosis Therapy

Evgeny N Antonov  1 , Sofya N Andreevskaya  2 , Irina V Bocharova  2 , Sergei E Bogorodsky  1 , Larisa I Krotova  1 , Elena E Larionova  2 , Alexandra O Mariyanats  1 , Gennady V Mishakov  1 , Tatiana G Smirnova  2 , Larisa N Chernousova  2 , Vladimir K Popov  1
Affiliations

PLGA Carriers for Controlled Release of Levofloxacin in Anti-Tuberculosis Therapy

Evgeny N Antonov et al. Pharmaceutics. .

Abstract

Levofloxacin (LFX) is a highly effective anti-tuberculosis drug with a pronounced bactericidal activity against Mycobacterium tuberculosis (Mtb). In this work, an "organic solvent-free" approach has been used for the development of polylactic-co-glycolic acid (PLGA) microparticles and scaffolds containing LFX at a therapeutically significant concentration, providing for its sustained release. To achieve the target, both nonpolar supercritical carbon dioxide and polar supercritical trifluoromethane have been used. By changing the composition, surface morphology, size, and internal structure of the polymer carriers, one can control the kinetics of the LFX release into phosphate buffered saline solutions and physiological media, providing for its acceptable burst and desirable concentration in the prolonged phase. The biocompatibility and bactericidal efficacy of PLGA/LFX carriers assessed both in vitro (against Mtb phagocytosed by macrophages) and in vivo (against inbred BALB/c mice aerogenically infected with Mtb) demonstrated their anti-tuberculosis activity comparable with that of the standard daily intragastric levofloxacin administration. These results make it possible to consider the developed compositions as a promising candidate for anti-tuberculosis control release formulations providing for the further evaluation of their activity against Mtb and their metabolism in vivo over long periods of tuberculosis infection.

Keywords: PLGA microparticles and scaffolds; anti-tuberculosis drugs; levofloxacin; supercritical fluid technologies; sustained release formulations.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Structural formula of LFX (left) and scanning electron microscopy (SEM) image of its initial particles (right).
Figure 2
Figure 2
SEM images of a PLGA/LFX fine powder mixture at two different magnifications.
Figure 3
Figure 3
SEM images of PLGA/LFX scaffolds fabricated using scCO2 (left) and scCHF3 (right).
Figure 4
Figure 4
SEM images of polymer microparticles produced by means of cryogrinding from PLGA/LFX scaffolds fabricated using scCO2 (left) and scCHF3 (right).
Figure 5
Figure 5
SEM images of PLGA/LFX microparticles produced by the PGSS technique using scCO2 (left) and scCHF3 (right).
Figure 6
Figure 6
Kinetics of the LFX release into the PBS from polyester scaffolds made of various PDLG brands using different SCFs.
Figure 7
Figure 7
Kinetics of LFX release from polymer microparticles produced by the PGSS technique and the cryogrinding of PLGA scaffolds fabricated using scCO2 and scCHF3.
Figure 8
Figure 8
Optical images of intact murine peritoneal macrophage cultures incubated together with and without PLGA/LFX microparticles or scaffolds for 7 days. 200× magnification. The arrows in (b,c) indicate PLGA/LFX microparticles. (a) Spontaneous MPh lysis. (b) Microparticles 12.5/0. (c) Microparticles 200/0. (d) Scaffold 500 μg. (e) Microparticles 1.25/0.125. (f) Microparticles 2.5/0.25. (g) Microparticles 5/0.5. (h) MPh infected with Mtb (30–40% lysis).
Figure 9
Figure 9
Time dependence of Mtb CFU/lung for different groups of mice.
See this image and copyright information in PMC

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