PLGA nanocapsules improve the delivery of clarithromycin to kill intracellular Staphylococcus aureus and Mycobacterium abscessus

Publication date: Available online 18 November 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Frantiescoli Anversa Dimer, Cristiane de Souza Carvalho-Wodarz, Adriely Goes, Katarina Cirnski, Jennifer Herrmann, Viktoria Schmitt, Linda Pätzold, Nadia Abed, Chiara De Rossi, Markus Bischoff, Patrick Couvreur, Rolf Müller, Claus-Michael LehrAbstractDrug 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.Graphical AbstractClarithromycin de...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research