Microencapsulated Isoniazid-Loaded Metal–Organic Frameworks for Pulmonary Administration of Antituberculosis Drugs

Tuberculosis (TB) is an infectious disease that causes a great number of deaths in the world (1.5 million people per year). This disease is currently treated by administering high doses of various oral anti-TB drugs for prolonged periods (up to 2 years). While this regimen is normally effective when...

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Autores principales: Cristina Fernández-Paz, Estefanía Fernández-Paz, Pablo Salcedo-Abraira, Sara Rojas, Sheila Barrios-Esteban, Noemi Csaba, Patricia Horcajada, Carmen Remuñán-López
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spelling oai:doaj.org-article:a9ca41a8dd55412b966565bcca81cf912021-11-11T18:25:41ZMicroencapsulated Isoniazid-Loaded Metal–Organic Frameworks for Pulmonary Administration of Antituberculosis Drugs10.3390/molecules262164081420-3049https://doaj.org/article/a9ca41a8dd55412b966565bcca81cf912021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6408https://doaj.org/toc/1420-3049Tuberculosis (TB) is an infectious disease that causes a great number of deaths in the world (1.5 million people per year). This disease is currently treated by administering high doses of various oral anti-TB drugs for prolonged periods (up to 2 years). While this regimen is normally effective when taken as prescribed, many people with TB experience difficulties in complying with their medication schedule. Furthermore, the oral administration of standard anti-TB drugs causes severe side effects and widespread resistances. Recently, we proposed an original platform for pulmonary TB treatment consisting of mannitol microspheres (Ma MS) containing iron (III) trimesate metal–organic framework (MOF) MIL-100 nanoparticles (NPs). In the present work, we loaded this system with the first-line anti-TB drug isoniazid (INH) and evaluated both the viability and safety of the drug vehicle components, as well as the cell internalization of the formulation in alveolar A549 cells. Results show that INH-loaded MOF (INH@MIL-100) NPs were efficiently microencapsulated in Ma MS, which displayed suitable aerodynamic characteristics for pulmonary administration and non-toxicity. MIL-100 and INH@MIL-100 NPs were efficiently internalized by A549 cells, mainly localized in the cytoplasm. In conclusion, the proposed micro-nanosystem is a good candidate for the pulmonary administration of anti-TB drugs.Cristina Fernández-PazEstefanía Fernández-PazPablo Salcedo-AbrairaSara RojasSheila Barrios-EstebanNoemi CsabaPatricia HorcajadaCarmen Remuñán-LópezMDPI AGarticleA549 cellsisoniazidmannitolmetal–organic frameworksmicroencapsulationpulmonary administrationOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6408, p 6408 (2021)
institution DOAJ
collection DOAJ
language EN
topic A549 cells
isoniazid
mannitol
metal–organic frameworks
microencapsulation
pulmonary administration
Organic chemistry
QD241-441
spellingShingle A549 cells
isoniazid
mannitol
metal–organic frameworks
microencapsulation
pulmonary administration
Organic chemistry
QD241-441
Cristina Fernández-Paz
Estefanía Fernández-Paz
Pablo Salcedo-Abraira
Sara Rojas
Sheila Barrios-Esteban
Noemi Csaba
Patricia Horcajada
Carmen Remuñán-López
Microencapsulated Isoniazid-Loaded Metal–Organic Frameworks for Pulmonary Administration of Antituberculosis Drugs
description Tuberculosis (TB) is an infectious disease that causes a great number of deaths in the world (1.5 million people per year). This disease is currently treated by administering high doses of various oral anti-TB drugs for prolonged periods (up to 2 years). While this regimen is normally effective when taken as prescribed, many people with TB experience difficulties in complying with their medication schedule. Furthermore, the oral administration of standard anti-TB drugs causes severe side effects and widespread resistances. Recently, we proposed an original platform for pulmonary TB treatment consisting of mannitol microspheres (Ma MS) containing iron (III) trimesate metal–organic framework (MOF) MIL-100 nanoparticles (NPs). In the present work, we loaded this system with the first-line anti-TB drug isoniazid (INH) and evaluated both the viability and safety of the drug vehicle components, as well as the cell internalization of the formulation in alveolar A549 cells. Results show that INH-loaded MOF (INH@MIL-100) NPs were efficiently microencapsulated in Ma MS, which displayed suitable aerodynamic characteristics for pulmonary administration and non-toxicity. MIL-100 and INH@MIL-100 NPs were efficiently internalized by A549 cells, mainly localized in the cytoplasm. In conclusion, the proposed micro-nanosystem is a good candidate for the pulmonary administration of anti-TB drugs.
format article
author Cristina Fernández-Paz
Estefanía Fernández-Paz
Pablo Salcedo-Abraira
Sara Rojas
Sheila Barrios-Esteban
Noemi Csaba
Patricia Horcajada
Carmen Remuñán-López
author_facet Cristina Fernández-Paz
Estefanía Fernández-Paz
Pablo Salcedo-Abraira
Sara Rojas
Sheila Barrios-Esteban
Noemi Csaba
Patricia Horcajada
Carmen Remuñán-López
author_sort Cristina Fernández-Paz
title Microencapsulated Isoniazid-Loaded Metal–Organic Frameworks for Pulmonary Administration of Antituberculosis Drugs
title_short Microencapsulated Isoniazid-Loaded Metal–Organic Frameworks for Pulmonary Administration of Antituberculosis Drugs
title_full Microencapsulated Isoniazid-Loaded Metal–Organic Frameworks for Pulmonary Administration of Antituberculosis Drugs
title_fullStr Microencapsulated Isoniazid-Loaded Metal–Organic Frameworks for Pulmonary Administration of Antituberculosis Drugs
title_full_unstemmed Microencapsulated Isoniazid-Loaded Metal–Organic Frameworks for Pulmonary Administration of Antituberculosis Drugs
title_sort microencapsulated isoniazid-loaded metal–organic frameworks for pulmonary administration of antituberculosis drugs
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/a9ca41a8dd55412b966565bcca81cf91
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