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

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    Research Article (1.806Mb)
    Date
    2015-06-06
    Author
    Lemmer, Yolandy
    Kalombo, Lonji
    Pietersen, Ray-Dean
    Jones, Arwyn T.
    Semete-Makokotlela, Boitumelo
    Van Wyngaardt, Sandra
    Ramalapa, Bathabile
    Stoltz, Anton C.
    Baker, Bienyameen
    Verschoor, Jan A.
    Swai, Hulda
    de Chastellier, Chantal
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    Abstract
    The appearance of drug-resistant strains of Mycobacterium tuberculosis (Mtb) poses a great challenge to the development of novel treatment programmes to combat tuberculosis. Since innovative nanotechnologiesmight 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 cellwallmycolic acids (MA) as targeting ligands into a drug-encapsulating Poly DL-lactic-co-glycolic acid polymer (PLGA), via a double emulsion solvent evaporation technique. Bonemarrow-derivedmousemacrophages, either uninfected or infectedwith differentmycobacterial strains (Mycobacterium avium, Mycobacterium bovis BCG or Mtb), 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) nanoparticle-containing phagosomes were rapidly processed into phagolysosomes, whether MA had been included or not; and iii) nanoparticlecontaining phagolysosomes did not fuse with non-matured mycobacterium-containing phagosomes, but fusion events with mycobacterium-containing phagolysosomes were clearly observed.
    URI
    http://dx.doi.org/10.1016/j.jconrel.2015.06.005
    http://dspace.nm-aist.ac.tz/handle/123456789/501
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