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Optimization and Application of an Efficient and Stable Inhalation Exposure System for Rodents

  • Research Article
  • Theme: Inhaled Drug Delivery of Biologics for Therapeutic and Vaccination
  • Published:
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ABSTRACT

Inhalation is a promising and challenging method in pharmaceutical and biological science research. A stable environment is critical in dynamic inhalation administration. However, the establishment of a stable inhalation system is very challenging. Indacaterol glycopyrronium bromide inhalation powder (IM/GP mixed powder) is composed of indacaterol maleate and glycopyrronium bromide powder to treat chronic obstructive pulmonary disease (COPD). The aim of this study is to build suitable inhalation conditions and then to evaluate the pulmonary safety of this drug in Sprague-Dawley(SD) rats. In the research, through the coordination of the atomization flow, air pump flow, and scraper speed, aerosols were stabilized at 200 ± 20% mg/m3, and then rats were nose-only administered with the IM/GP mixed powder, Ultibro, and lactose-magnesium stearate mixed powder at 2.6 mg/kg/day for 14 days and 14 days of recovery period, respectively. After exposure, hematology, inflammatory cytokines in rats bronchoalveolar lavage fluid (BALF) and serum, histopathological examination were performed. Results showed that the stability of powder aerosols can be realized under the atomization generation flow: 10 L/min, sampling flow: 2 L/min, system pumping capacity: 10 L/min and powder scraper speed: 8–10 L/min, and there were no significant adverse effects on body weight, clinic signs, hematology, and pathology in rats. Overall, the results suggested that the IM/GP mixed powder inhalation at the dose of 2.6 mg/kg/d can be reached when the aerosol concentration is within the range of 200 ± 20% mg/m3, and there were no pulmonary toxicity effects in rats.

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Data availability

The data presented in this study are available upon request.

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Acknowledgements

The authors thank Yangteng Ou (University of Cambridge, UK) for some proofreading work.

Funding

This work was supported by the National Natural Science Foundation of China under Grant (81773479), the National Major Science and Technology Projects of China under Grant (2017ZX09201002-004), and the research project of Jiangsu Commission of Health (H201634).

Author information

Author notes

  1. Zi Fan and Bo Zhou contributed equally to this work.

Authors and Affiliations

  1. The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China

    Zi Fan & Qian Bian

  2. Jiangsu Center for Safety Evaluation of Drugs, Jiangsu Province Institute of Materia Medica, School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, 211800, China

    Bo Zhou, Wu Sun & Yuntao Fang

  3. Medical School, Nanjing University, Nanjing, 210093, China

    Yujia Liu

  4. Respirent Pharmaceuticals Co., Ltd, No. 5, Yuntu Road, Beibei District, Chongqing, 400714, China

    Hongguo Lu

  5. Institute of Toxicology and Risk Assessment, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, China

    Dongya Chen, Kuikui Lu, Xinyue Wu, Tian Xiao & Qian Bian

  6. Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China

    Wenjing Xie

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Contributions

ZF: methodology, investigation, validation, data curation, writing—original draft. BZ: methodology, validation, investigation, writing—review and editing. YL: methodology, investigation, validation, writing—review and editing. WS: methodology, investigation, formal analysis. YF: validation, resources, data curation. HL: formal analysis, writing—review and editing. DC: validation, writing—review and editing. KL: validation, writing—review and editing. XW: writing—review and editing. TX: writing—review and editing. WX: resources, writing—review and editing. QB: conceptualization, resources, writing—review and editing, supervision, project administration, funding acquisition. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Qian Bian.

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Fan, Z., Zhou, B., Liu, Y. et al. Optimization and Application of an Efficient and Stable Inhalation Exposure System for Rodents. AAPS PharmSciTech 23, 50 (2022). https://doi.org/10.1208/s12249-021-02191-8

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