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Potential Active Targeting of Gatifloxacin to Macrophages by Means of Surface-Modified PLGA Microparticles Destined to Treat Tuberculosis

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Abstract

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis and represents one of the leading causes of mortality worldwide due to multidrug-resistant TB (MDR-TB). In our work, a new formulation of biodegradable PLGA microparticles was developed for pulmonary administration of gatifloxacin, using a surface modifier agent to actively target alveolar macrophages thereby allowing to gain access of the drug to Mycobacterium tuberculosis. For this, rapid uptake of the particles by macrophages is beneficial. This process was evaluated with fluorescein-loaded microparticles using PLGA 502 or PLGA 502H as polymers and labrafil as surface modifier. Cell phagocytosis was studied in raw 264.7 mouse macrophage cell line after 3, 5, 24, and 48 h incubation with the microparticles. Labrafil enhanced the uptake rate of PLGA 502H microparticles by macrophages which was directly related to the modification of the polymer matrix. Gatifloxacin-loaded PLGA microparticles using PLGA 502 or PLGA 502H and labrafil were prepared. From our results, only microparticles prepared with PLGA 502H and labrafil exhibited high encapsulation efficiency (89.6 ± 0.2%), rapid phagocytosis by macrophages (3 h), and remained inside the cells for at least 48 h, thereby resulting in a suitable carrier to potentially treat MDR-TB.

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Acknowledgments

The authors wish to express their gratitude to Isabel Trabado from the Unidad de Cultivos de Células Humanas (Universidad de Alcalá, Spain) for her technical assistance.

Funding

This work was partially supported by the Complutense University of Madrid, UCM Research group 910.939.

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Authors and Affiliations

  1. Departamento de Farmacia Galénica y Tecnología Alimentaria, Facultad de Farmacia, Pl. Ramón y Cajal s/n, Universidad Complutense de Madrid, 28040, Madrid, Spain

    Patricia Marcianes, Sofia Negro, Emilia Barcia & Ana Fernández-Carballido

  2. Facultad de Farmacia, Pl. Ramón y Cajal s/n, Instituto Universitario de Farmacia Industrial, Universidad Complutense de Madrid, 28040, Madrid, Spain

    Sofia Negro, Emilia Barcia & Ana Fernández-Carballido

  3. Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, 28668 Boadilla del Monte, Madrid, Spain

    Consuelo Montejo

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  1. Patricia Marcianes
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  2. Sofia Negro
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Correspondence to Sofia Negro.

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All animal procedures were conducted according to the European Community Council Directive (010/63/UE).

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Marcianes, P., Negro, S., Barcia, E. et al. Potential Active Targeting of Gatifloxacin to Macrophages by Means of Surface-Modified PLGA Microparticles Destined to Treat Tuberculosis. AAPS PharmSciTech 21, 15 (2020). https://doi.org/10.1208/s12249-019-1552-3

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