Inhalable Antitubercular Therapy Mediated by Locust Bean Gum Microparticles

• Published in: Molecules (Basel, Switzerland) Vol. 21; no. 6; p. 702
• Main Authors: Alves, Ana D, Cavaco, Joana S, Guerreiro, Filipa, Lourenço, João P, Rosa da Costa, Ana M, Grenha, Ana
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28-05-2016; MDPI
• Subjects: A549 Cells; Administration, Inhalation; alveolar macrophages; Antitubercular Agents - administration & dosage; Antitubercular Agents - adverse effects; Antitubercular Agents - chemistry; antitubercular drugs; Cytotoxicity; Drug Delivery Systems; Drugs; Galactans - administration & dosage; Galactans - adverse effects; Galactans - chemistry; Humans; inhalable therapy; locust bean gum; Macrophages, Alveolar - drug effects; Macrophages, Alveolar - pathology; Mannans - administration & dosage; Mannans - adverse effects; Mannans - chemistry; microparticles; Microspheres; Mycobacterium; Mycobacterium tuberculosis - drug effects; Particle Size; Phagocytosis - drug effects; Plant Gums - administration & dosage; Plant Gums - adverse effects; Plant Gums - chemistry; spray-drying; Tuberculosis; Tuberculosis - drug therapy; tuberculosis therapy; Portugal; alveolar macrophages; inhalable therapy; microparticles; tuberculosis therapy; antitubercular drugs; locust bean gum; spray-drying
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules21060702

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.