Inhalable Antitubercular Therapy Mediated by Locust Bean Gum Microparticles
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 phagocyt...
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| Format: | Article |
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MDPI AG
2016-05-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/21/6/702 |
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| author | Ana D. Alves Joana S. Cavaco Filipa Guerreiro João P. Lourenço Ana M. Rosa da Costa Ana Grenha |
| author_facet | Ana D. Alves Joana S. Cavaco Filipa Guerreiro João P. Lourenço Ana M. Rosa da Costa Ana Grenha |
| author_sort | Ana D. Alves |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T00:17:24Z |
| format | Article |
| id | doaj.art-e9777817e6a84cfbac90dd46a1a63a5a |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-13T00:17:24Z |
| publishDate | 2016-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-e9777817e6a84cfbac90dd46a1a63a5a2022-12-22T03:10:55ZengMDPI AGMolecules1420-30492016-05-0121670210.3390/molecules21060702molecules21060702Inhalable Antitubercular Therapy Mediated by Locust Bean Gum MicroparticlesAna D. Alves0Joana S. Cavaco1Filipa Guerreiro2João P. Lourenço3Ana M. Rosa da Costa4Ana Grenha5Center for Biomedical Research (CBMR), Faculty of Sciences and Technology, University of Algarve, 8005-139 Faro, PortugalCenter for Biomedical Research (CBMR), Faculty of Sciences and Technology, University of Algarve, 8005-139 Faro, PortugalCenter for Biomedical Research (CBMR), Faculty of Sciences and Technology, University of Algarve, 8005-139 Faro, PortugalCentro de Química Estrutural (CQE), Instituto Superior Técnico, University of Lisbon, 1049-001 Lisbon, PortugalAlgarve Chemistry Research Center (CIQA) and Department of Chemistry and Pharmacy, Faculty of Sciences and Technology, University of Algarve, 8005-139 Faro, PortugalCenter for Biomedical Research (CBMR), Faculty of Sciences and Technology, University of Algarve, 8005-139 Faro, PortugalTuberculosis 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.http://www.mdpi.com/1420-3049/21/6/702alveolar macrophagesantitubercular drugsinhalable therapylocust bean gummicroparticlesspray-dryingtuberculosis therapy |
| spellingShingle | Ana D. Alves Joana S. Cavaco Filipa Guerreiro João P. Lourenço Ana M. Rosa da Costa Ana Grenha Inhalable Antitubercular Therapy Mediated by Locust Bean Gum Microparticles Molecules alveolar macrophages antitubercular drugs inhalable therapy locust bean gum microparticles spray-drying tuberculosis therapy |
| title | Inhalable Antitubercular Therapy Mediated by Locust Bean Gum Microparticles |
| title_full | Inhalable Antitubercular Therapy Mediated by Locust Bean Gum Microparticles |
| title_fullStr | Inhalable Antitubercular Therapy Mediated by Locust Bean Gum Microparticles |
| title_full_unstemmed | Inhalable Antitubercular Therapy Mediated by Locust Bean Gum Microparticles |
| title_short | Inhalable Antitubercular Therapy Mediated by Locust Bean Gum Microparticles |
| title_sort | inhalable antitubercular therapy mediated by locust bean gum microparticles |
| topic | alveolar macrophages antitubercular drugs inhalable therapy locust bean gum microparticles spray-drying tuberculosis therapy |
| url | http://www.mdpi.com/1420-3049/21/6/702 |
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