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.
Highlights
There is an effective treatment for tuberculosis (TB), the disease remains one of the major health problems worldwide [1]
The cytotoxic evaluation of Locust bean gum (LBG) microparticles was performed in two cell lines of the alveolar environment, epithelial A549 cells and macrophage-differentiated THP-1 cells
The graphics depicting the analysis of the populations corresponding to cells of determination of its ability for preferential macrophage capture would be provided by a comparison each line not exposed to fluorescently-labelled LBG microparticles
Summary
There is an effective treatment for tuberculosis (TB), the disease remains one of the major health problems worldwide [1]. In 2014, the World Health Organization reported 9.6 million new cases of TB [2], infection caused by inhalation of aerosol particles containing Mycobacterium tuberculosis (MTB) bacilli [1]. The inhaled bacilli are phagocytosed by alveolar macrophages, which triggers a series of events that can lead to either control of the infection, i.e., latent TB, or progression to an active form of the disease [1]. 80% of cases, of theofdesign of antitubercular formulations is considered an therapeutic adequate therapeutic thecases, design antitubercular inhalable inhalable formulations is considered an adequate approach. Inhalable therapy allows the co-localisation of drugs and pathogens and to enable. Inhalable therapy allows the co-localisation of drugs and pathogens and is thoughtistothought enable increased increased drug concentration in along the lungs, withlung-to-plasma favoured lung-to-plasma ratio.
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