Mycolic acids, a promising mycobacterial ligand for targeting of nanoencapsulated drugs in tuberculosis

Yolandy Lemmer, Lonji Kalombo, Ray-Dean Pietersen, Arwyn T. Jones, Boitumelo Semete-Makokotlela, Sandra Van Wyngaardt, Bathabile Ramalapa, Anton C. Stoltz, Bienyameen Baker, Jan A. Verschoor, Hulda S. Swai, Chantal de Chastellier
2015 Journal of Controlled Release  
The appearance of drug-resistant strains of Mycobacterium tuberculosis (M. tb) poses a great challenge to the development of novel treatment programmes to combat tuberculosis. Since innovative nanotechnologies might alleviate the limitations of current therapies, we have designed a new nanoformulation for use as an anti-TB drug delivery system. It consists of incorporating mycobacterial cell wall mycolic acids (MA) as targeting ligands into a drug-encapsulating Poly DL-lactic-coglycolic acid
more » ... ymer (PLGA), via a double emulsion solvent evaporation technique. Bone marrow-derived mouse macrophages, either uninfected or infected with different mycobacterial strains (M. avium, M. bovis BCG or M. tb), were exposed to encapsulated isoniazid-PLGA nanoparticles (NPs) using MA as a targeting ligand. The fate of the NPs was monitored by electron microscopy. Our study showed that i) the inclusion of MA in the nanoformulations resulted in their expression on the outer surface and a significant increase in phagocytic uptake of the NPs; ii) nanoparticlecontaining phagosomes were rapidly processed into phagolysosomes, whether MA had been included or not; iii) nanoparticle-containing phagolysosomes did not fuse with non-matured mycobacterium-containing phagosomes, but fusion events with mycobacterium-containing phagolysosomes were clearly observed.
doi:10.1016/j.jconrel.2015.06.005 pmid:26055640 fatcat:cy3zdkqr4ndxxcnwhulu74zdsm