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PLGA nanocapsules improve the delivery of clarithromycin to kill intracellular Staphylococcus aureus and Mycobacterium abscessus.
Anversa Dimer, Frantiescoli de Souza Carvalho-Wodarz, Cristiane Goes, Adriely Cirnski, Katarina Herrmann, Jennifer Schmitt, Viktoria Pätzold, Linda Abed, Nadia de Rossi, Chiara Bischoff, Markus
Anversa Dimer, Frantiescoli
de Souza Carvalho-Wodarz, Cristiane
Goes, Adriely
Cirnski, Katarina
Herrmann, Jennifer
Schmitt, Viktoria
Pätzold, Linda
Abed, Nadia
de Rossi, Chiara
Bischoff, Markus
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2019-11-18
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original manuscript
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supplementary data
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supplementary table S1
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Abstract
Drug delivery systems are promising for targeting antibiotics directly to infected tissues. To reach intracellular Staphylococcus aureus and Mycobacterium abscessus, we encapsulated clarithromycin in PLGA nanocapsules, suitable for aerosol delivery by nebulization of an aqueous dispersion. Compared to the same dose of free clarithromycin, nanoencapsulation reduced 1000 times the number of intracellular S. aureus in vitro. In RAW cells, while untreated S. aureus was located in acidic compartments, the treated ones were mostly situated in non-acidic compartments. Clarithromycin-nanocapsules were also effective against M. abscessus (70-80% killing efficacy). The activity of clarithromycin-nanocapsules against S. aureus was also confirmed in vivo, using a murine wound model as well as in zebrafish. The permeability of clarithromycin-nanocapsules across Calu-3 monolayers increased in comparison to the free drug, suggesting an improved delivery to sub-epithelial tissues. Thus, clarithromycin-nanocapsules are a promising strategy to target intracellular S. aureus and M. abscessus.
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Nanomedicine. 2019 Nov 18;24:102125. doi: 10.1016/j.nano.2019.102125.
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Article
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en
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1549-9642
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Attribution-NonCommercial-ShareAlike 4.0 International