In vitro behaviour of konjac glucomannan microparticles aimed at pulmonary tuberculosis therapy

Tuberculosis is one of the highest causes of death worldwide. Long periods of treatment are required and result in some cases in therapeutic incompliance, potentiating the development of multidrug-resistant tuberculosis. Thus, new approaches to treat the infection are required as an alternative to conventional orally administered treatment. This work proposes the development of an inhalable system, which is specifically targeted to alveolar macrophages, where the Mycobacterium tuberculosis is located. The targeting is mainly driven by the selected matrix material, konjac glucomannan (KGM), a natural polymer comprising mannan units that are expected to potentiate phagocytosis. Microparticles were loaded with two antitubercular drugs, isoniazid (INH) and rifabutin (RFB). KGM/INH/RFB microparticles were produced by spray-drying to produce particles with suitable characteristics to deliver INH and RFB to the alveolar region. The KGM/INH/RFB microparticles possessed an aerodynamic diameter of approximately 3 µm, meeting the requirement of a therapy targeted to alveolar macrophages. Moreover, KGM microparticles exhibited suitable geometric size (2.24 µm) and shape (spherical) to be phagocytosed to deliver drugs to infected macrophages. INH and RFB were associated with KGM microparticles with efficiencies of 91% and 74%, respectively. Similar in vitro release profiles were observed for both drugs in simulated lung fluid (SLF) replicating the lining fluid composition found in human alveoli.Funding from the Portuguese Foundation for Science and Technology (UID/Multi/04326/2019, UID/BIM/04773/2013, Pest-OE/QUI/UI4023/2014), and the PhD scholarship to Filipa Guerreiro (SFRH/BD/115628/2016) are acknowledged.