Dual antibiotherapy of tuberculosis mediated by inhalable locust bean gum microparticles

作者：Rodrigues Susana; Alves Ana D; Cavaco Joana S; Pontes Jorge F; Guerreiro Filipa; Rosa da Costa Ana M; Buttini Francesca; Grenha Ana

来源：International Journal of Pharmaceutics, 2017, 529(1-2): 433-441.

DOI：10.1016/j.ijpharm.2017.06.088

• Inhalation
• Locust bean gum
• Microparticles
• Polysaccharides
• Spray-drying
• Tuberculosis therapy

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.

• 出版日期2017-8-30