Inhalable Nanomedicine for Treatment of Pulmonary Tuberculosis
Khaled H. Alzahabi1, Theoni K. Georgiou2, Hisham Al-Obaidi3, Brian D. Robertson4, Omar Usmani1, Alexandra E. Porter2 and Teresa D. Tetley1
1National Heart and Lung Institute, Imperial College London, London, UK.
2Department of Materials and London Centre for Nanotechnology, Imperial College London, London, UK.
3College of Pharmacy, University of Reading, Reading, UK.
4MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, UK.
Summary
Tuberculosis (TB) is currently treated using a cocktail of antituberculosis (anti-TB) drugs for between 6 and 24 months. The systemic side effects and lack of compliance can lead to multidrug resistant TB (MDR-TB). A faster, simpler more reliable therapy is urgently required to reduce both the drug dose and period of treatment, to improve patient compliance and reduce MDR-TB. To this end, we have constructed an inhalable anti-TB formulation to target Mycobacterium tuberculosis (M.tb) in the airways and in particular the deep lung. The aim was to assemble poly (lactic-co-glycolic acid) microparticles to carry silver nanoparticles (AgNPs) associated with rifampicin (RIF) in an aerosolised microparticle form to be delivered directly to the lungs by inhalation. The safety of the microparticles at the human alveolar respiratory gas-liquid interface was determined using transformed primary human alveolar epithelial cells with type 1 cell-like characteristics (TT1). The synthesised AgNPs were spherical, with a mean diameter of 15-18 nm. A concentration ≤10 mg/ml of AgNPs in serum free medium did not cause TT1 cell death. PLGA microparticles containing AgNPs and RIF were generated using solvent evaporation method and fully characterised for their size, charge and AgNP/RIF content. The microparticle constructs were spherical with diameter less than 5 µm (median 1.35 µm). RIF and AgNPs were successfully encapsulated within the PLGA microparticles with an encapsulation percentage of 79% and 53% respectively. The next step is to assess the safety of this delivery system against M.tb alone and against M.tb-infected models of TT1 epithelial cells and human lung macrophages.
Key Message
We have generated a microparticle drug delivery system for co-delivery of antibiotic rifampicin and silver nanoparticles by inhalation to improve the current TB treatment regimen, that is safe to human lung cells, will lower drug dose and reduce treatment times so reducing MDR-TB.