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

Molecules

Pablo Salcedo-Abraira¹  Sara Rojas¹  Patricia Horcajada¹  Estefanía Fernández-Paz²  Cristina Fernández-Paz²  Carmen Remuñán-López²  Noemi Csaba³  Sheila Barrios-Esteban³ 

[1]Advanced Porous Materials Unit (APMU), IMDEA Energy Institute, Av. Ramón de la Sagra, 3, 28035 Móstoles, Madrid, Spain

[2]Nanobiofar Group, Department of Pharmacology, Pharmacy & Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Campus Vida, 15782 Santiago de Compostela, Galicia, Spain

[3]Nanobiofar Group-Natural Polymers and Biomimetics (NPNB) Group, Center of Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela, Campus Vida, 15706 Santiago de Compostela, Galicia, Spain

关键词: A549 cells;    isoniazid;    mannitol;    metal–organic frameworks;    microencapsulation;    pulmonary administration;   

DOI  :  10.3390/molecules26216408

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown