Wang Kai, Chen Dagui, Zhang Chenxi, Lu Lu, Shang Fusheng, Li Yinghua
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Institute of Translational Medicine, Shanghai University, Shanghai 200444, China.
Polymers (Basel). 2024 May 12;16(10):1384. doi: 10.3390/polym16101384.
Acute pneumonia (AP), triggered primarily by pathogens like bacteria and viruses, is a leading cause of human mortality. Ribavirin, a broad-spectrum antiviral agent, plays a pivotal role in the treatment of AP. However, its therapeutic use is hindered by the need for high dosages and the associated cardiac and hepatic toxicities. In this study, we synthesized polyethylene glycol-modified cationic liposomes to encapsulate ribavirin (RBV-PCL) and formulated it into a spray, aiming to enhance the effectiveness of RBV through respiratory administration. Lipopolysaccharide (LPS), a compound known to induce AP models in animals, was utilized in our research. Successfully, we established an acute pneumonia model in mice using aerosol inhalation. Through animal experiments, we investigated the therapeutic effects of RBV-PCL on mice with AP. In vivo studies revealed promising results. RBV-PCL effectively prolonged the survival of mice with AP, significantly reduced the levels of inflammatory markers such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and inhibited the infiltration of neutrophils in the lungs and spleens of mice. These findings suggest that RBV-PCL can effectively suppress the inflammatory response in mice with AP, thus holding significant potential as a novel therapeutic approach for the treatment of acute pneumonia.
急性肺炎（AP）主要由细菌和病毒等病原体引发，是人类死亡的主要原因。利巴韦林作为一种广谱抗病毒药物，在急性肺炎的治疗中起着关键作用。然而，其治疗应用受到高剂量需求以及相关心脏和肝脏毒性的限制。在本研究中，我们合成了聚乙二醇修饰的阳离子脂质体来包裹利巴韦林（RBV-PCL），并将其制成喷雾剂，旨在通过呼吸道给药提高利巴韦林的疗效。脂多糖（LPS）是一种已知可在动物中诱导急性肺炎模型的化合物，被用于我们的研究。我们成功地通过气溶胶吸入在小鼠中建立了急性肺炎模型。通过动物实验，我们研究了RBV-PCL对急性肺炎小鼠的治疗效果。体内研究显示出了有前景的结果。RBV-PCL有效延长了急性肺炎小鼠的存活时间，显著降低了白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）等炎症标志物的水平，并抑制了小鼠肺和脾中中性粒细胞的浸润。这些发现表明，RBV-PCL可有效抑制急性肺炎小鼠的炎症反应，因此作为治疗急性肺炎的一种新型治疗方法具有巨大潜力。
