A novel non-invasive murine model for rapidly testing drug activity via inhalation administration against Mycobacterium tuberculosis
The efficacy of many compounds against Mycobacterium tuberculosis is often limited when administered via conventional oral or injection routes due to suboptimal pharmacokinetic characteristics. Inhalation-based delivery methods have been investigated to achieve high local therapeutic doses in the lu...
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2025-01-01
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| author | Xirong Tian Xirong Tian Xirong Tian Xirong Tian Yamin Gao Yamin Gao Yamin Gao Yamin Gao Chunyu Li Chunyu Li Chunyu Li Chunyu Li Wanli Ma Wanli Ma Wanli Ma Wanli Ma Jingran Zhang Jingran Zhang Jingran Zhang Jingran Zhang Yanan Ju Yanan Ju Yanan Ju Yanan Ju Jie Ding Jie Ding Jie Ding Jie Ding Sanshan Zeng Sanshan Zeng Sanshan Zeng Sanshan Zeng H. M. Adnan Hameed H. M. Adnan Hameed H. M. Adnan Hameed H. M. Adnan Hameed Htin Lin Aung Htin Lin Aung Htin Lin Aung Nanshan Zhong Gregory M. Cook Gregory M. Cook Gregory M. Cook Gregory M. Cook Jinxing Hu Jinxing Hu Tianyu Zhang Tianyu Zhang Tianyu Zhang Tianyu Zhang Tianyu Zhang |
| author_facet | Xirong Tian Xirong Tian Xirong Tian Xirong Tian Yamin Gao Yamin Gao Yamin Gao Yamin Gao Chunyu Li Chunyu Li Chunyu Li Chunyu Li Wanli Ma Wanli Ma Wanli Ma Wanli Ma Jingran Zhang Jingran Zhang Jingran Zhang Jingran Zhang Yanan Ju Yanan Ju Yanan Ju Yanan Ju Jie Ding Jie Ding Jie Ding Jie Ding Sanshan Zeng Sanshan Zeng Sanshan Zeng Sanshan Zeng H. M. Adnan Hameed H. M. Adnan Hameed H. M. Adnan Hameed H. M. Adnan Hameed Htin Lin Aung Htin Lin Aung Htin Lin Aung Nanshan Zhong Gregory M. Cook Gregory M. Cook Gregory M. Cook Gregory M. Cook Jinxing Hu Jinxing Hu Tianyu Zhang Tianyu Zhang Tianyu Zhang Tianyu Zhang Tianyu Zhang |
| author_sort | Xirong Tian |
| collection | DOAJ |
| description | The efficacy of many compounds against Mycobacterium tuberculosis is often limited when administered via conventional oral or injection routes due to suboptimal pharmacokinetic characteristics. Inhalation-based delivery methods have been investigated to achieve high local therapeutic doses in the lungs. However, previous models, typically employing wild-type M. tuberculosis strains, were intricate, time-consuming, labor-intensive, and with poor reproducibility. In this study, we developed an autoluminescence-based inhalation administration model to evaluate drug activity by quantifying relative light units (RLUs) emitted from live mice infected with autoluminescent M. tuberculosis. This novel approach offers several advantages: (1) it eliminates the need for anesthesia in mice during administration and simplifies the instrument manipulation; (2) it is cost-effective by utilizing mice instead of larger animals; (3) it shortens the time from several months to 16 or 17 days for obtaining result; (4) it is non-invasive by directly measuring the live RLUs of mice as a surrogate marker for colony-forming units for in vivo drug activity testing; (5) up to six mice can be administrated daily and simultaneously, even 2–3 times/day; (6) results are relatively objective and reproducible results minimizing human factors. Proof-of-concept experiments demonstrated that inhalable rifampicin, isoniazid, and ethambutol showed anti-M. tuberculosis activity at concentrations as low as 0.5, 0.5, and 0.625 mg/mL, respectively, as evidenced by comparing the live RLUs of mice. Furthermore, consistency between RLUs and colony-forming units of the autoluminescent M. tuberculosis in lungs reaffirms the reliability of RLUs as an indicator of drug efficacy, highlighting the potential of this approach for accurately assessing anti-M. tuberculosis activity in vivo. This autoluminescence-based, non-invasive inhalation model offers a substantial reduction in the time, effort, and cost required for evaluating the efficacy of screening new drugs and repurposing old drugs in vivo via inhalation administration. |
| format | Article |
| id | doaj-art-2f9eb6e75fbf482ab3ce79385de7d6ed |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-2f9eb6e75fbf482ab3ce79385de7d6ed2025-01-03T06:47:06ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.14004361400436A novel non-invasive murine model for rapidly testing drug activity via inhalation administration against Mycobacterium tuberculosisXirong Tian0Xirong Tian1Xirong Tian2Xirong Tian3Yamin Gao4Yamin Gao5Yamin Gao6Yamin Gao7Chunyu Li8Chunyu Li9Chunyu Li10Chunyu Li11Wanli Ma12Wanli Ma13Wanli Ma14Wanli Ma15Jingran Zhang16Jingran Zhang17Jingran Zhang18Jingran Zhang19Yanan Ju20Yanan Ju21Yanan Ju22Yanan Ju23Jie Ding24Jie Ding25Jie Ding26Jie Ding27Sanshan Zeng28Sanshan Zeng29Sanshan Zeng30Sanshan Zeng31H. M. Adnan Hameed32H. M. Adnan Hameed33H. M. Adnan Hameed34H. M. Adnan Hameed35Htin Lin Aung36Htin Lin Aung37Htin Lin Aung38Nanshan Zhong39Gregory M. Cook40Gregory M. Cook41Gregory M. Cook42Gregory M. Cook43Jinxing Hu44Jinxing Hu45Tianyu Zhang46Tianyu Zhang47Tianyu Zhang48Tianyu Zhang49Tianyu Zhang50State Key Laboratory of Respiratory Disease, Joint School of Life Sciences, Guangzhou Chest Hospital, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, ChinaUniversity of Chinese Academy of Sciences (UCAS), Beijing, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Joint School of Life Sciences, Guangzhou Chest Hospital, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, ChinaUniversity of Chinese Academy of Sciences (UCAS), Beijing, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Joint School of Life Sciences, Guangzhou Chest Hospital, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, ChinaUniversity of Chinese Academy of Sciences (UCAS), Beijing, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Joint School of Life Sciences, Guangzhou Chest Hospital, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, ChinaUniversity of Chinese Academy of Sciences (UCAS), Beijing, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Joint School of Life Sciences, Guangzhou Chest Hospital, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, ChinaUniversity of Chinese Academy of Sciences (UCAS), Beijing, ChinaSchool of Life Sciences, University of Science and Technology of China, Hefei, ChinaState Key Laboratory of Respiratory Disease, Joint School of Life Sciences, Guangzhou Chest Hospital, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, ChinaUniversity of Chinese Academy of Sciences (UCAS), Beijing, ChinaSchool of Life Sciences, University of Science and Technology of China, Hefei, ChinaState Key Laboratory of Respiratory Disease, Joint School of Life Sciences, Guangzhou Chest Hospital, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, ChinaUniversity of Chinese Academy of Sciences (UCAS), Beijing, ChinaInstitute of Physical Science and Information Technology, Anhui University, Hefei, ChinaState Key Laboratory of Respiratory Disease, Joint School of Life Sciences, Guangzhou Chest Hospital, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, ChinaUniversity of Chinese Academy of Sciences (UCAS), Beijing, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Joint School of Life Sciences, Guangzhou Chest Hospital, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, ChinaUniversity of Chinese Academy of Sciences (UCAS), Beijing, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaDepartment of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, Dunedin, New ZealandMaurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New ZealandGuangzhou National Laboratory, Guangzhou, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaDepartment of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, Dunedin, New ZealandMaurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand0Translational Research Institute, Queensland University of Technology, Brisbane, QLD, AustraliaState Key Laboratory of Respiratory Disease, Joint School of Life Sciences, Guangzhou Chest Hospital, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, ChinaGuangzhou National Laboratory, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Joint School of Life Sciences, Guangzhou Chest Hospital, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, ChinaUniversity of Chinese Academy of Sciences (UCAS), Beijing, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangzhou National Laboratory, Guangzhou, ChinaThe efficacy of many compounds against Mycobacterium tuberculosis is often limited when administered via conventional oral or injection routes due to suboptimal pharmacokinetic characteristics. Inhalation-based delivery methods have been investigated to achieve high local therapeutic doses in the lungs. However, previous models, typically employing wild-type M. tuberculosis strains, were intricate, time-consuming, labor-intensive, and with poor reproducibility. In this study, we developed an autoluminescence-based inhalation administration model to evaluate drug activity by quantifying relative light units (RLUs) emitted from live mice infected with autoluminescent M. tuberculosis. This novel approach offers several advantages: (1) it eliminates the need for anesthesia in mice during administration and simplifies the instrument manipulation; (2) it is cost-effective by utilizing mice instead of larger animals; (3) it shortens the time from several months to 16 or 17 days for obtaining result; (4) it is non-invasive by directly measuring the live RLUs of mice as a surrogate marker for colony-forming units for in vivo drug activity testing; (5) up to six mice can be administrated daily and simultaneously, even 2–3 times/day; (6) results are relatively objective and reproducible results minimizing human factors. Proof-of-concept experiments demonstrated that inhalable rifampicin, isoniazid, and ethambutol showed anti-M. tuberculosis activity at concentrations as low as 0.5, 0.5, and 0.625 mg/mL, respectively, as evidenced by comparing the live RLUs of mice. Furthermore, consistency between RLUs and colony-forming units of the autoluminescent M. tuberculosis in lungs reaffirms the reliability of RLUs as an indicator of drug efficacy, highlighting the potential of this approach for accurately assessing anti-M. tuberculosis activity in vivo. This autoluminescence-based, non-invasive inhalation model offers a substantial reduction in the time, effort, and cost required for evaluating the efficacy of screening new drugs and repurposing old drugs in vivo via inhalation administration.https://www.frontiersin.org/articles/10.3389/fphar.2024.1400436/fullinhalation administrationautoluminescencetuberculosismurine modelchemotherapy |
| spellingShingle | Xirong Tian Xirong Tian Xirong Tian Xirong Tian Yamin Gao Yamin Gao Yamin Gao Yamin Gao Chunyu Li Chunyu Li Chunyu Li Chunyu Li Wanli Ma Wanli Ma Wanli Ma Wanli Ma Jingran Zhang Jingran Zhang Jingran Zhang Jingran Zhang Yanan Ju Yanan Ju Yanan Ju Yanan Ju Jie Ding Jie Ding Jie Ding Jie Ding Sanshan Zeng Sanshan Zeng Sanshan Zeng Sanshan Zeng H. M. Adnan Hameed H. M. Adnan Hameed H. M. Adnan Hameed H. M. Adnan Hameed Htin Lin Aung Htin Lin Aung Htin Lin Aung Nanshan Zhong Gregory M. Cook Gregory M. Cook Gregory M. Cook Gregory M. Cook Jinxing Hu Jinxing Hu Tianyu Zhang Tianyu Zhang Tianyu Zhang Tianyu Zhang Tianyu Zhang A novel non-invasive murine model for rapidly testing drug activity via inhalation administration against Mycobacterium tuberculosis Frontiers in Pharmacology inhalation administration autoluminescence tuberculosis murine model chemotherapy |
| title | A novel non-invasive murine model for rapidly testing drug activity via inhalation administration against Mycobacterium tuberculosis |
| title_full | A novel non-invasive murine model for rapidly testing drug activity via inhalation administration against Mycobacterium tuberculosis |
| title_fullStr | A novel non-invasive murine model for rapidly testing drug activity via inhalation administration against Mycobacterium tuberculosis |
| title_full_unstemmed | A novel non-invasive murine model for rapidly testing drug activity via inhalation administration against Mycobacterium tuberculosis |
| title_short | A novel non-invasive murine model for rapidly testing drug activity via inhalation administration against Mycobacterium tuberculosis |
| title_sort | novel non invasive murine model for rapidly testing drug activity via inhalation administration against mycobacterium tuberculosis |
| topic | inhalation administration autoluminescence tuberculosis murine model chemotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1400436/full |
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