{"title":"负载利福平的新型金属-有机骨架改善肺部输送的吸入电位:理化特性、体外雾化和抗细菌研究。","authors":"Sima Kujur, Arti Singh, Charan Singh","doi":"10.1089/jamp.2022.0002","DOIUrl":null,"url":null,"abstract":"<p><p><b><i>Background:</i></b> 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. <b><i>Materials and Methods:</i></b> 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, <i>in vitro</i> release, powder flow characterization, <i>in vitro</i> lung deposition, and efficacy studies against the <i>Mycobacterium tuberculosis</i> (MTB) H37Rv strain were performed. <b><i>Results:</i></b> Physicochemical characterization confirms its spherical shape and drug loading, whereas <i>in vitro</i> 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, <i>in vitro</i> 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 <i>in vitro</i> 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) <i>vis-à-vis</i> an unformulated drug (0.025 mg/mL) against the MTB H37Rv strain, using the BACTEC 460TB system. <b><i>Conclusions:</i></b> Therefore, MOFs could be promising nanocarriers for targeting lungs and overcoming the hepatotoxicity associated with antituberculosis drugs requiring inhalation administration.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"35 5","pages":"259-268"},"PeriodicalIF":2.0000,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"4","resultStr":"{\"title\":\"Inhalation Potential of Rifampicin-Loaded Novel Metal-Organic Frameworks for Improved Lung Delivery: Physicochemical Characterization, <i>In Vitro</i> Aerosolization and Antimycobacterial Studies.\",\"authors\":\"Sima Kujur, Arti Singh, Charan Singh\",\"doi\":\"10.1089/jamp.2022.0002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b><i>Background:</i></b> 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. <b><i>Materials and Methods:</i></b> 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, <i>in vitro</i> release, powder flow characterization, <i>in vitro</i> lung deposition, and efficacy studies against the <i>Mycobacterium tuberculosis</i> (MTB) H37Rv strain were performed. <b><i>Results:</i></b> Physicochemical characterization confirms its spherical shape and drug loading, whereas <i>in vitro</i> 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, <i>in vitro</i> 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 <i>in vitro</i> 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) <i>vis-à-vis</i> an unformulated drug (0.025 mg/mL) against the MTB H37Rv strain, using the BACTEC 460TB system. <b><i>Conclusions:</i></b> Therefore, MOFs could be promising nanocarriers for targeting lungs and overcoming the hepatotoxicity associated with antituberculosis drugs requiring inhalation administration.</p>\",\"PeriodicalId\":14940,\"journal\":{\"name\":\"Journal of Aerosol Medicine and Pulmonary Drug Delivery\",\"volume\":\"35 5\",\"pages\":\"259-268\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2022-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Aerosol Medicine and Pulmonary Drug Delivery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1089/jamp.2022.0002\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"RESPIRATORY SYSTEM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/jamp.2022.0002","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
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.
期刊介绍:
Journal of Aerosol Medicine and Pulmonary Drug Delivery is the only peer-reviewed journal delivering innovative, authoritative coverage of the health effects of inhaled aerosols and delivery of drugs through the pulmonary system. The Journal is a forum for leading experts, addressing novel topics such as aerosolized chemotherapy, aerosolized vaccines, methods to determine toxicities, and delivery of aerosolized drugs in the intubated patient.
Journal of Aerosol Medicine and Pulmonary Drug Delivery coverage includes:
Pulmonary drug delivery
Airway reactivity and asthma treatment
Inhalation of particles and gases in the respiratory tract
Toxic effects of inhaled agents
Aerosols as tools for studying basic physiologic phenomena.