Dual antibiotherapy of tuberculosis mediated by inhalable locust bean gum microparticles.
Despite the existence of effective oral therapy, tuberculosis remains a deadly pathology, namely because of bacterial resistance and incompliance with treatments. Establishing alternative therapeutic approaches is urgently needed and inhalable therapy has a great potential in this regard. As pathogenic bacteria are hosted by alveolar macrophages, the co-localisation of antitubercular drugs and pathogens is thus potentiated by this strategy. This work proposes inhalable therapy of pulmonary tuberculosis mediated by a single locust bean gum (LBG) formulation of microparticles associating both isoniazid and rifabutin, complying with requisites of the World Health Organisation of combined therapy. Microparticles were produced by spray-drying, at LBG/INH/RFB mass ratio of 10/1/0.5. The aerodynamic characterisation of microparticles revealed emitted doses of more than 90% and fine particle fraction of 38%, thus indicating the adequacy of the system to reach the respiratory lung area, thus partially the alveolar region. Cytotoxicity results indicate moderate toxicity (cell viability around 60%), with a concentration-dependent effect. Additionally, rat alveolar macrophages evidenced preferential capture of LBG microparticles, possibly due to chemical composition comprising mannose and galactose units that are specifically recognised by macrophage surface receptors.
['Rodrigues|Susana|S|', 'Alves|Ana D|AD|', 'Cavaco|Joana S|JS|', 'Pontes|Jorge F|JF|', 'Guerreiro|Filipa|F|', 'Rosa da Costa|Ana M|AM|', 'Buttini|Francesca|F|', 'Grenha|Ana|A|']
D000280:Administration, Inhalation D000818:Animals D000995:Antitubercular Agents D002460:Cell Line D004337:Drug Carriers D005685:Galactans D006801:Humans D007538:Isoniazid D008351:Mannans D053149:Plant Gums D051381:Rats D017828:Rifabutin D014376:Tuberculosis
Inhalation Locust bean gum Microparticles Spray-drying Polysaccharides Tuberculosis therapy