1. Fucosylated lipid nanocarriers loaded with antibiotics efficiently inhibit mycobacterial propagation in human myeloid cells
- Author
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Bernd Lepenies, Elena Grabski, Nicole Koller, Hanzey Yasar, Theresa Graalmann, Bibiana Costa, Jennifer Becker, Yvonne Lueder, João T. Monteiro, Constantin Hozsa, Marcus Furch, Gudrun Brandes, Robert Tampé, Ulrich Kalinke, Bettina Wiegmann, Volkhard Kaever, Reinhold Förster, Berislav Bošnjak, Claus-Michael Lehr, Verónica Durán, TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany., and HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
- Subjects
Alveolar macrophages ,Tuberculosis ,medicine.drug_class ,Endosome ,Antibiotics ,Pharmaceutical Science ,02 engineering and technology ,Microbiology ,Mycobacterium tuberculosis ,03 medical and health sciences ,medicine ,Humans ,030304 developmental biology ,Targeted drug delivery ,0303 health sciences ,Liposome ,biology ,Chemistry ,Macrophages ,021001 nanoscience & nanotechnology ,biology.organism_classification ,medicine.disease ,Lipids ,In vitro ,Anti-Bacterial Agents ,Nanomedicine ,Liposomes ,Nanocarriers ,0210 nano-technology - 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.
- Published
- 2021