A Metal-Organic Framework (MOF) dry powder technology for antibiotic deep lung delivery and imaging

Gabriela Wyszogrodzka¹, Przemysław Dorożyński², Piotr Kulinowski³ & Stefano Giovagnoli⁴

¹Department of Pharmacobiology Jagiellonian University Medical College, Medyczna 9, 30-068 Kraków, Poland

²Pharmaceutical Research Institute, Rydygiera 8, 01-793 Warszawa, Poland

³Department of Magnetic Resonance Imaging, Institute of Nuclear Physics, Polish Academy of Sciences, Radzikowskiego 152, 31-342 Kraków, Poland

⁴Department of Pharmaceutical Sciences, via del Liceo 1, University of Perugia, Perugia, 06123, Italy

Summary

The use of the theranostic approach could allow effective delivery and imaging of dry powders in the lungs for a better control and personalization of antibiotic therapy. In this work, we employed the Metal-Organic Frameworks (MOFs) technology to develop a dry powder blend with suitable aerodynamic properties and drug release behavior. The presence of Fe can allow tracking of particle deposition in the airways while granting adequate drug delivery. Isoniazid was employed as a model drug and loaded onto Fe-MIL-101-NH₂ MOF. This isoniazid-MOF complex was embedded into a blend of poly(lactide-co-glycolide) and leucine microparticles. A high loading and content uniformity was pursued in both microparticles. A factorial experimental design study determined the predominant effect of blending ratio compared to MOF content and blending time on the measured fine particle fraction. Final blends showed good aerodynamic properties (fine particle fraction > 50%) and isoniazid-MOF content uniformity (%RSD < 7%), as also observed by energy dispersive X-rays spectroscopy, in spite of a rather irregular morphology, certain fragility and broad size distribution of the particles. The in vitro isoniazid release was slower than expected with only 12% of drug released within the first 24 h. This was linked to a slow liberation of isoniazid from the MOF.

Overall, the obtained blends showed promising features compatible with lung deposition imaging purposes even in light of the good Magnetic Resonance Imaging contrast capacity of MOF. This formulation strategy could be useful for the development of an effective personalized pulmonary therapy.