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用托珠单抗雾化吸入的BALB/c小鼠呼吸道和肝脏的组织学评估

Histological Assessment of Respiratory Tract and Liver of BALB/c Mice Nebulized with Tocilizumab.

作者信息

de Andres Paloma Jimena, Ferreiro Sergio, Flores Angela, Garcia Almudena, Henriquez-Camacho Cesar

机构信息

Departamento de Medicina y Cirugía Animal, Facultad de Veterinaria de la, Universidad Complutense de Madrid, 28040 Madrid, Spain.

Unidad de Veterinaria, Radiodiagnóstico y Cirugía Experimental del, Centro de Apoyo Tecnológico de la, Facultad de Ciencias de la Salud de la, Universidad Rey Juan Carlos, 28922 Alcorcon, Spain.

出版信息

Pharmaceutics. 2024 Jun 27;16(7):862. doi: 10.3390/pharmaceutics16070862.

Abstract

Pulmonary drug delivery offers a minimally invasive and efficient method for treating lung conditions, leveraging the lungs' extensive surface area and blood flow for rapid drug absorption. Nebulized therapies aim to deliver drugs directly to the lung tissue. This study investigates the histological impact of nebulized tocilizumab-a monoclonal antibody targeting IL-6, traditionally administered intravenously for rheumatoid arthritis and severe COVID-19-on a murine model. Thirty BALB/c mice were nebulized with tocilizumab (10 mg, 5 mg, and 2.5 mg) and six controls were nebulized with saline solution. They were euthanized 48 h later, and their organs (lungs, nasal mucosa, and liver) were analyzed by a microscopic histological evaluation. The results indicate that all the mice survived the 48 h post-nebulization period without systemic compromise. The macroscopic examination showed no abnormalities, and the histopathological analysis revealed greater lung vascular changes in the control group than in the nebulized animals, which is attributable to the euthanasia with carbon dioxide. Additionally, increased alveolar macrophages were observed in the nebulized groups compared to controls. No significant histological changes were observed in the liver, indicating the safety of nebulized tocilizumab. In conclusion, these findings suggest the potential of nebulized tocilizumab for treating pulmonary inflammation, warranting further research to establish its efficacy and safety in clinical settings.

摘要

肺部给药提供了一种微创且高效的治疗肺部疾病的方法,利用肺部广泛的表面积和血流实现药物的快速吸收。雾化疗法旨在将药物直接递送至肺组织。本研究调查了雾化托珠单抗(一种靶向白细胞介素-6的单克隆抗体,传统上用于静脉注射治疗类风湿性关节炎和重症新型冠状病毒肺炎)对小鼠模型的组织学影响。30只BALB/c小鼠用托珠单抗(10毫克、5毫克和2.5毫克)进行雾化,6只对照小鼠用盐溶液进行雾化。48小时后对它们实施安乐死,并通过显微镜组织学评估分析它们的器官(肺、鼻黏膜和肝脏)。结果表明,所有小鼠在雾化后48小时内存活,且无全身功能障碍。大体检查未发现异常,组织病理学分析显示,与雾化动物相比,对照组的肺部血管变化更大,这归因于二氧化碳安乐死。此外,与对照组相比,雾化组观察到肺泡巨噬细胞增多。肝脏未观察到明显的组织学变化,表明雾化托珠单抗具有安全性。总之,这些发现提示雾化托珠单抗治疗肺部炎症的潜力,有必要进一步研究以确定其在临床环境中的疗效和安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6474/11280351/ee1f84fb17df/pharmaceutics-16-00862-g001.jpg

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