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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.
Despite all advances in drug delivery, the limitations of the analytical technologies involved in the characterization of next-generation nanomedicines are still impeding further progress of an emerging market. Discriminating between different formulations and batches, drug release is one of the most important quality criteria in development and quality control of pharmaceutics. Unfortunately, there are only few methods available to sensitively measure this important parameter for nanosized carriers. With the development of the dispersion releaser (DR) technology our group has set up a dialysis-based technique that was tested with a number of nanocarrier and nanocrystal formulations such as liposomes and polymeric nanoparticles. By supporting formulation development with a more reliable methodology to assess the drug release from nanosized carriers, a first step has been made to improve future products.