Targeted intracellular delivery of antitubercular agents by functionalized nanocapsules

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Tuberculosis (TB) is still a major public health problem worldwide. It is estimated that more than one-quarter of the world's population is infected with this airborne infectious disease. Moreover, the increase of multidrug- and extensively drug-resistant TB is alarming. TB is caused by Mycobacterium tuberculosis, an intracellular pathogen that can survive in host cells, mainly in macrophages. The uptake of the antitubercular drugs by infected host cells is limited. The orally or intravenously administered drugs are distributed throughout the body causing side effects and the majority of the drug molecules do not reach their targets. The elimination of the intracellular bacteria could be more efficient with host cell directed delivery. The TBNANO project aims to develop and in vitro evaluate antitubercular agent-loaded nanocapsules decorated with host cell targeting molecules. For this purpose, naturally occurring, biocompatible and biodegradable polysaccharide nanocapsules loaded with a recently approved anti-TB drug (bedaquiline) and antimicrobial peptides will be used. The surface of the nanocapsules will be functionalized with macrophage targeting ligands, such as peptides and mannose derivatives. With such nanotechnology-based drug delivery system, enhanced cellular uptake can be achieved by the host cell macrophages, therefore, the anti-TB agent can reach the intracellular bacteria as site of action. This approach leads to increased bioavailability and selectivity of the drugs while reducing their undesirable side effects. The proposed project could provide a breakthrough step in nanotechnology-based TB treatment to get closer to a world free of TB. Furthermore, this multidisciplinary project provide valuable transfer of knowledge to the host institution, as well as advanced training of the young researcher in the field of nanomaterial science to broaden her expertise in drug delivery systems.