PDF(Pubmed)
Abstract：
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.
摘要：
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,广谱抗病毒药物,在AP的治疗中起着举足轻重的作用。然而,由于需要高剂量以及相关的心脏和肝脏毒性，其治疗用途受到阻碍。在这项研究中,我们合成了聚乙二醇修饰的阳离子脂质体来封装利巴韦林（RBV-PCL）并将其配制成喷雾剂，旨在通过呼吸给药提高RBV的有效性。脂多糖（LPS），一种已知在动物中诱导AP模型的化合物，在我们的研究中使用。成功,采用雾化吸入法建立小鼠急性肺炎模型。通过动物实验,我们研究了RBV-PCL对AP小鼠的治疗作用。体内研究揭示了有希望的结果。RBV-PCL能有效延长AP小鼠的生存期,显着降低炎症标志物如白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的水平，并抑制小鼠肺和脾脏中中性粒细胞的浸润。提示RBV-PCL能有效抑制AP小鼠的炎症反应,因此，作为治疗急性肺炎的一种新的治疗方法具有巨大的潜力。
