title: 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.affiliation: Polymers and Composites, Council for Scientific and Industrial Research, Pretoria, South Africa. Electronic address: ylemmer@csir.co.za.
authors.forename: Yolandy
authors.initials: Y
authors.lastname: Lemmer
authors.affiliation: Polymers and Composites, Council for Scientific and Industrial Research, Pretoria, South Africa.
authors.forename: Lonji
authors.initials: L
authors.lastname: Kalombo
authors.affiliation: DST-CBTBR Department Molecular Biology and Human Genetics, Stellenbosch University, Cape Town, South Africa.
authors.forename: Ray-Dean
authors.initials: RD
authors.lastname: Pietersen
authors.affiliation: Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Wales, UK.
authors.forename: Arwyn T
authors.initials: AT
authors.lastname: Jones
authors.affiliation: Polymers and Composites, Council for Scientific and Industrial Research, Pretoria, South Africa.
authors.forename: Boitumelo
authors.initials: B
authors.lastname: Semete-Makokotlela
authors.affiliation: Department of Biochemistry, University of Pretoria, Pretoria, South Africa.
authors.forename: Sandra
authors.initials: S
authors.lastname: Van Wyngaardt
authors.affiliation: Polymers and Composites, Council for Scientific and Industrial Research, Pretoria, South Africa.
authors.forename: Bathabile
authors.initials: B
authors.lastname: Ramalapa
authors.affiliation: Department of Infectious Diseases, University of Pretoria, Pretoria, South Africa.
authors.forename: Anton C
authors.initials: AC
authors.lastname: Stoltz
authors.affiliation: DST-CBTBR Department Molecular Biology and Human Genetics, Stellenbosch University, Cape Town, South Africa.
authors.forename: Bienyameen
authors.initials: B
authors.lastname: Baker
authors.affiliation: Department of Biochemistry, University of Pretoria, Pretoria, South Africa.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Verschoor
authors.affiliation: Polymers and Composites, Council for Scientific and Industrial Research, Pretoria, South Africa.
authors.forename: Hulda S
authors.initials: HS
authors.lastname: Swai
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Aix Marseille University, UM 2, INSERM UMR 1104, CNRS UMR 7280, 163 avenue de Luminy, 13288 Marseille Cedex 09, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: de Chastellier
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000187:drug effects / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000378:metabolism; D009171:Mycolic Acids / Q000008:administration & dosage* / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage* / Q000378:metabolism; D014376:Tuberculosis / Q000188:drug therapy / Q000378:metabolism
chemical_list: D000995:Antitubercular Agents; D008024:Ligands; D009171:Mycolic Acids
keywords: Electron microscopy; Mycolic acids; Nanodrug delivery; Phagosomes; Targeting; Tuberculosis