Respirable konjac glucomannan microparticles as antitubercular drug carriers: Effects of in vitro and in vivo interactions

Pulmonary delivery of drugs is potentially beneficial in the context of lung disease, maximising drug concentrations in the site of action. A recent work proposed spray-dried konjac glucomannan (KGM) microparticles as antitubercular drug (isoniazid and rifabutin) carriers to treat pulmonary tuberculosis. The present work explores in vitro and in vivo effects of these microparticles, focusing on the ability for macrophage uptake, the exhibited antibacterial activity and safety issues. Efficient uptake of KGM microparticles by macrophages was demonstrated in vitro, while the antitubercular activity of the model drugs against Mycobacterium bovis was not affected by microencapsulation in KGM microparticles. Despite the good indications provided by the developed system, KGM is not yet approved for pulmonary applications, which is a limiting characteristic. To reinforce the available data on the performance of the material, safety parameters were evaluated both in vitro and in vivo, showing promising results. No significant cell toxicity was observed at concentrations considered realistic for lung delivery approaches (up to 125 & mu;g/mL) when lung epithelial cells and macrophages were exposed to KGM microparticles (both drug-loaded and unloaded). Finally, no signs of systemic or lung inflammatory response were detected in mice after receiving 10 administrations of unloaded KGM microparticles.

Automated summary

This study investigates the use of spray-dried konjac glucomannan (KGM) microparticles as carriers for antitubercular drugs to treat pulmonary tuberculosis. The results show that KGM microparticles are efficiently taken up by macrophages, and microencapsulation does not affect the activity of the drugs against Mycobacterium bovis. In vitro and in vivo safety evaluations show no significant cell toxicity or inflammatory response after exposure to KGM microparticles.