Inhalation Potential of Rifampicin-Loaded Novel Metal-Organic Frameworks for Improved Lung Delivery: Physicochemical Characterization, In Vitro Aerosolization and Antimycobacterial Studies.

Background

The aim of the current study was to examine the potential of a rifampicin-loaded metal-organic framework (RIF@ZIF-8) for management of tuberculosis. Materials and

Methods

RIF@ZIF-8 was developed using a simple, economic, and environmentally friendly ultrasonication method. Furthermore, the developed metal-organic framework (MOF) formulations were subjected to physicochemical characterization analyses such as Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffractometry, thermogravimetric analysis, field emission-scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), and UV spectroscopy. In addition, in vitro release, powder flow characterization, in vitro lung deposition, and efficacy studies against the Mycobacterium tuberculosis (MTB) H37Rv strain were performed.

Results

Physicochemical characterization confirms its spherical shape and drug loading, whereas in vitro release analysis shows 80.5 ± 5.5% release of the drug from the loaded formulation within 48 hours. Furthermore, powder flow properties suggested that the nature of MOFs is free flowing. Additionally, in vitro lung deposition studies indicated an emission fraction of 88.02 ± 10.23% for the emitted dose and circa 21% fine particle fraction. The mass median aerodynamic diameter and geometric standard deviation were found to be 4.42 ± 0.07 μm and 1.55 ± 01 μm, respectively. The in vitro aerosol performance study demonstrated higher deposition at stages 3, 4, and 5 of the cascade impactors, which simulate deep lung delivery in terms of the trachea-primary bronchus and secondary and terminal bronchi of the human lung, respectively. Moreover, RIF@ZIF-8 exhibited improved antimycobacterial activity (0.0125 mg/mL) vis-à-vis an unformulated drug (0.025 mg/mL) against the MTB H37Rv strain, using the BACTEC 460TB system.

Conclusions

Therefore, MOFs could be promising nanocarriers for targeting lungs and overcoming the hepatotoxicity associated with antituberculosis drugs requiring inhalation administration.