• 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; et al. (Elsevier, 2021-04-16)
      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.
    • Spray-dried lactose-leucine microparticles for pulmonary delivery of antimycobacterial nanopharmaceuticals.

      Thiyagarajan, Durairaj; Huck, Benedikt; Nothdurft, Birgit; Koch, Marcus; Rudolph, David; Rutschmann, Mark; Feldmann, Claus; Hozsa, Constantin; Furch, Marcus; Besecke, Karen F W; et al. (2021-06-08)
    • The synergistic effect of chlorotoxin-mApoE in boosting drug-loaded liposomes across the BBB.

      Formicola, Beatrice; Dal Magro, Roberta; Montefusco-Pereira, Carlos V; Lehr, Claus-Michael; Koch, Marcus; Russo, Laura; Grasso, Gianvito; Deriu, Marco A; Danani, Andrea; Bourdoulous, Sandrine; et al. (BMC, 2019-11-11)
      We designed liposomes dually functionalized with ApoE-derived peptide (mApoE) and chlorotoxin (ClTx) to improve their blood-brain barrier (BBB) crossing. Our results demonstrated the synergistic activity of ClTx-mApoE in boosting doxorubicin-loaded liposomes across the BBB, keeping the anti-tumour activity of the drug loaded: mApoE acts promoting cellular uptake, while ClTx promotes exocytosis of liposomes.