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.
