title: Inhalable Antitubercular Therapy Mediated by Locust Bean Gum Microparticles.
abstract: Tuberculosis remains a major global health problem and alternative therapeutic approaches are needed. Considering the high prevalence of lung tuberculosis (80% of cases), the pulmonary delivery of antitubercular drugs in a carrier system capable of reaching the alveoli, being recognised and phagocytosed by alveolar macrophages (mycobacterium hosts), would be a significant improvement to current oral drug regimens. Locust bean gum (LBG) is a polysaccharide composed of galactose and mannose residues, which may favour specific recognition by macrophages and potentiate phagocytosis. LBG microparticles produced by spray-drying are reported herein for the first time, incorporating either isoniazid or rifabutin, first-line antitubercular drugs (association efficiencies >82%). Microparticles have adequate theoretical properties for deep lung delivery (aerodynamic diameters between 1.15 and 1.67 μm). The cytotoxic evaluation in lung epithelial cells (A549 cells) and macrophages (THP-1 cells) revealed a toxic effect from rifabutin-loaded microparticles at the highest concentrations, but we may consider that these were very high comparing with in vivo conditions. LBG microparticles further evidenced strong ability to be captured by macrophages (percentage of phagocytosis >94%). Overall, the obtained data indicated the potential of the proposed system for tuberculosis therapy.
authors.affiliation: Center for Biomedical Research (CBMR), Faculty of Sciences and Technology, University of Algarve, 8005-139 Faro, Portugal. anabdiasalves@gmail.com.
authors.forename: Ana D
authors.initials: AD
authors.lastname: Alves
authors.affiliation: Center for Biomedical Research (CBMR), Faculty of Sciences and Technology, University of Algarve, 8005-139 Faro, Portugal. joanasofiacavaco@gmail.com.
authors.forename: Joana S
authors.initials: JS
authors.lastname: Cavaco
authors.affiliation: Center for Biomedical Research (CBMR), Faculty of Sciences and Technology, University of Algarve, 8005-139 Faro, Portugal. filiparhg@gmail.com.|Centre for Marine Sciences (CCMar), University of Algarve, 8005-139 Faro, Portugal. filiparhg@gmail.com.
authors.forename: Filipa
authors.initials: F
authors.lastname: Guerreiro
authors.affiliation: Centro de Qu&#237;mica Estrutural (CQE), Instituto Superior T&#233;cnico, University of Lisbon, 1049-001 Lisbon, Portugal. jlouren@ualg.pt.|Algarve Chemistry Research Center (CIQA) and Department of Chemistry and Pharmacy, Faculty of Sciences and Technology, University of Algarve, 8005-139 Faro, Portugal. jlouren@ualg.pt.
authors.forename: João P
authors.initials: JP
authors.lastname: Lourenço
authors.affiliation: Algarve Chemistry Research Center (CIQA) and Department of Chemistry and Pharmacy, Faculty of Sciences and Technology, University of Algarve, 8005-139 Faro, Portugal. amcosta@ualg.pt.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Rosa da Costa
authors.affiliation: Center for Biomedical Research (CBMR), Faculty of Sciences and Technology, University of Algarve, 8005-139 Faro, Portugal. amgrenha@ualg.pt.|Centre for Marine Sciences (CCMar), University of Algarve, 8005-139 Faro, Portugal. amgrenha@ualg.pt.
authors.forename: Ana
authors.initials: A
authors.lastname: Grenha
mesh_terms: D000072283:A549 Cells; D000280:Administration, Inhalation; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D016503:Drug Delivery Systems; D005685:Galactans / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D006801:Humans; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000473:pathology; D008351:Mannans / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D008863:Microspheres; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects; D053149:Plant Gums / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D005685:Galactans; D008351:Mannans; D053149:Plant Gums; C017471:locust bean gum
keywords: alveolar macrophages; antitubercular drugs; inhalable therapy; locust bean gum; microparticles; spray-drying; tuberculosis therapy