The theranostic approach to local tuberculosis treatment allows drug delivery and imaging of the lungs for a better control and personalization of antibiotic therapy. Metal-organic framework (MOF) Fe-MIL-101-NH2 nanoparticles were loaded with isoniazid. To optimize their functionality a 23 factorial design of spray-drying with poly(lactide-co-glycolide) and leucine was employed. Powder aerodynamic properties were assessed using a twin stage impinger based on the dose emitted and the fine particle fraction. Magnetic resonance imaging (MRI) contrast capabilities were tested on porous lung tissue phantom and ex vivo rat lungs. Cell viability and uptake studies were conducted on murine macrophages RAW 246.9. The final product showed good aerodynamic properties, modified drug release, easier uptake by macrophages in relation to raw isoniazid-MOF, and MRI contrast capabilities. Starting from raw MOF, a fully functional inhalable theranostic system with a potential application in personalized tuberculosis pulmonary therapy was developed.
Keywords: inhalable spray-dried powder blends; inhaled microparticles; isoniazid (INH); local pulmonary delivery; metal-organic frameworks (MOF); personalized inhaled therapy; porous lung tissue phantom; theranostic agent; tuberculosis (TB); ultrashort echo time magnetic resonance imaging (UTE MRI).