Fucosylated lipid nanocarriers loaded with antibiotics efficiently inhibit mycobacterial propagation in human myeloid cells

  • 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.
Author:Verónica Durán MejíaGND, Elena GrabskiGND, Constantin HozsaORCiD, Jennifer BeckerORCiD, Hanzey Yasar, João T. Monteiro, Bibiana Costa, Nicole KollerGND, Yvonne Lueder, Bettina Pamela WiegmannGND, Gudrun BrandesORCiDGND, Volkhard KaeverGND, Claus-Michael LehrORCiDGND, Bernd LepeniesGND, Robert TampéORCiDGND, Reinhold FörsterORCiDGND, Berislav BošnjakORCiD, Marcus Furch, Theresa GraalmannORCiDGND, Ulrich KalinkeORCiDGND
Parent Title (English):Journal of controlled release
Place of publication:New York, NY [u.a.]
Document Type:Article
Date of Publication (online):2021/04/16
Date of first Publication:2021/04/16
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/01/09
Tag:Alveolar macrophages; Liposomes; Nanomedicine; Targeted drug delivery; Tuberculosis
Page Number:12
First Page:201
Last Page:212
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0