An Inhalable Theranostic System for Local Tuberculosis Treatment Containing an Isoniazid Loaded Metal Organic Framework Fe-MIL-101-NH2—From Raw MOF to Drug Delivery System

Gabriela Wyszogrodzka-Gaweł,Władysław P Węglarz,Piotr Kulinowski,Edyta Pesta,Barbara Gil,Stefano Giovagnoli,Przemysław Dorożyński,Weronika Strzempek,Elżbieta Menaszek

doi:10.3390/pharmaceutics11120687

Abstract

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.

Highlights

The deceptive nature of tuberculosis (TB) contributed to its long-time reputation of curable and defeated disease
Our preliminary studies have shown that INH-loaded Metal-organic framework (MOF) (INH-MOF) display insufficient aerodynamic performances to stand alone as an inhaled dosage form
In order to meet the fundamental requirements of proper nebulization, deposition, and pulmonary retention, INH-MOF was encapsulated in hydrophobic poly(lactide-co-glycolide) (PLGA) MPs by spray-drying and blended with spray-dried INH-MOFloaded D-leucine (LC) MPs

Summary

Introduction

The deceptive nature of tuberculosis (TB) contributed to its long-time reputation of curable and defeated disease. Alongside poor health care settings and treatment control, limited understanding of TB infection peculiarities and the complex host-pathogen crosstalk have crippled progresses in the field. Current therapies rely on cumbersome, lengthy multidrug treatments that, albeit still effective at early infection stages, lose efficacy rapidly at later disease phases and on latent infections. A dramatic but inevitable consequence is the alarming worldwide growth of drug resistance that has undermined the sustainability and efficacy of current TB treatments. This scenario partially explains the general crisis of the antibiotic drug market. A renewed awareness and increased knowledge of TB infection features have encouraged recent efforts towards the development of host-directed approaches and inhaled TB therapies. Pulmonary anti-TB drug delivery is the logical strategy for maintaining local therapeutically effective concentrations while avoiding massive systemic exposure and reducing side effects [1,2]

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