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

Lemmer, Yolandy, Kalombo, Lonji, Pietersen, Ray-Dean, Jones, Arwyn Tomos, Semete-Makokotlela, Boitumelo, Van Wyngaardt, Sandra, Ramalapa, Bathabile, Stoltz, Anton C., Baker, Bienyameen, Verschoor, Jan A., Swai, Hulda S. and de Chastellier, Chantal 2015. Mycolic acids, a promising mycobacterial ligand for targeting of nanoencapsulated drugs in tuberculosis. Journal of Controlled Release 211 , pp. 94-104. 10.1016/j.jconrel.2015.06.005

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RM Therapeutics. Pharmacology
Additional Information: Online publication: 6 June 2015
Publisher: Elsevier
ISSN: 0168-3659
Funders: South African Department of Science and Technology, South African National Research Foundation and South African Council for Scientific and Industrial Research, Cardiff University, Institut National de la Santé et de la Recherche Médicale (INSERM) and the Centre National de la Recherche Scientifique (CNRS) to the Centre d'Immunologie de Marseille-Luminy (CIML) and by grant ANR-09-MIEN-009-03 from the Agence Nationale de la Recherche
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 4 June 2015
Last Modified: 04 Jun 2017 08:11

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