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

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 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-co-glycolic acid polymer (PLGA), via a double emulsion solvent evaporation technique. Bone marrow-derived mouse macrophages, either uninfected or infected with different mycobacterial 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) nanoparticle-containing phagolysosomes did not fuse with non-matured mycobacterium-containing phagosomes, but fusion events with mycobacterium-containing phagolysosomes were clearly observed.

• Authors: 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
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 211 Pg. 94-104 (Aug 10 2015) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 26055640 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Antitubercular Agents
• Ligands
• Mycolic Acids

Topics

• Animals
• Antitubercular Agents (administration & dosage, metabolism)
• Drug Delivery Systems (methods)
• Female
• Humans
• Ligands
• Mice
• Mice, Inbred C57BL
• Mycobacterium bovis (drug effects, metabolism)
• Mycobacterium tuberculosis (drug effects, metabolism)
• Mycolic Acids (administration & dosage, metabolism)
• Nanoparticles (administration & dosage, metabolism)
• Tuberculosis (drug therapy, metabolism)