Fucosylated lipid nanocarriers loaded with antibiotics efficiently inhibit mycobacterial propagation in human myeloid cells
Verónica Durán, Elena Grabski, Constantin Hozsa, Jennifer Becker, Hanzey Yasar, João T. Monteiro, Bibiana Costa, Nicole Koller, Yvonne Lueder, Bettina Wiegmann, Gudrun Brandes, Volkhard Kaever, Claus‐Michael Lehr, Bernd Lepenies, Robert Tampé, Reinhold Förster, Berislav Bošnjak, Marcus Furch, Theresa Graalmann, Ulrich Kalinke
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.