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Fucosylated lipid nanocarriers loaded with antibiotics efficiently inhibit mycobacterial propagation in human myeloid cells.
Durán, Verónica Grabski, Elena Hozsa, Constantin Becker, Jennifer Yasar, Hanzey Monteiro, João T Costa, Bibiana Koller, Nicole Lueder, Yvonne Wiegmann, Bettina
Durán, Verónica
Grabski, Elena
Hozsa, Constantin
Becker, Jennifer
Yasar, Hanzey
Monteiro, João T
Costa, Bibiana
Koller, Nicole
Lueder, Yvonne
Wiegmann, Bettina
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2021-04-16
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Open Access article
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Open Access article
Adobe PDF, 10.17 MB
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Abstract
Antibiotic treatment of tuberculosis (TB) is complex, lengthy, and can be associated with various adverse effects. As a result, patient compliance often is poor, thus further enhancing the risk of selecting multi-drug resistant bacteria. Macrophage mannose receptor (MMR)-positive alveolar macrophages (AM) constitute a niche in which Mycobacterium tuberculosis replicates and survives. Therefore, we encapsulated levofloxacin in lipid nanocarriers functionalized with fucosyl residues that interact with the MMR. Indeed, such nanocarriers preferentially targeted MMR-positive myeloid cells, and in particular, AM. Intracellularly, fucosylated lipid nanocarriers favorably delivered their payload into endosomal compartments, where mycobacteria reside. In an in vitro setting using infected human primary macrophages as well as dendritic cells, the encapsulated antibiotic cleared the pathogen more efficiently than free levofloxacin. In conclusion, our results point towards carbohydrate-functionalized nanocarriers as a promising tool for improving TB treatment by targeted delivery of antibiotics.
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J Control Release. 2021 Jun 10;334:201-212. doi: 10.1016/j.jconrel.2021.04.012. Epub 2021 Apr 16.
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en
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1873-4995
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Attribution 4.0 International