Konjac glucomannan microparticles for antitubercular drug delivery by inhalation
Filipa Guerreiro1,2, Ana M Rosa da Costa3, Maria Leonor Faleiro1 & Ana Grenha1,2
1CBMR – Centre for Biomedical Research, Drug Delivery Laboratory, University of Algarve, Campus de Gambelas, Faro, 8005-139, Portugal
2CCMAR – Centre of Marine Sciences, University of Algarve, Campus de Gambelas, Faro, 8005-139, Portugal
3Algarve Chemistry Research Centre (CIQA) and Department of Chemistry and Pharmacy, Faculty of Sciences and Technology, University of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal
Summary
Tuberculosis (TB) remains a deadly disease worldwide, although effective oral antibiotherapy is available. Frequent reports on systemic toxicity associated with the therapy, as well as emergence of multidrug resistant tuberculosis (MDR-TB) may partly justify the active state of the disease. As Mycobacterium tuberculosis (Mtb), the infectious agent, is transmitted via inhalation and primarily accumulates in the alveolar macrophages, pulmonary delivery of antitubercular drugs appears as a possible solution to circumvent some of the limitations. In this work, konjac glucomannan (KGM) is proposed as matrix material of spray-dried microparticles tailored to exhibit suitable properties to reach the alveoli. The presence of mannose units in the polymer and the geometric size of microparticles (Feret’s diameter of 1.39 µm) are expected to favour macrophage uptake. Isoniazid (INH) and rifabutin (RFB), two first-line antitubercular drugs, were efficiently associated in combination to KGM microcarriers (association efficiencies of 89.8% and 67.1%, respectively). The biocompatibility of KGM and KGM-based microparticles on macrophage-like THP-1 cells was evaluated by the MTT and the lactate dehydrogenase (LDH) release assays. Neither drug-loaded microparticles nor KGM itself induced significant cytotoxicity. The obtained results are encouraging to further evaluate INH/RFB-loaded KGM microparticles for an application as delivery system in TB therapy.
