Han Meishan, Song Yingjian, Liu Sha, Lu Xiaoyan, Su Linyu, Liu Meixuan, Zhu Xiaosu, Sun Kaoxiang, Lu Yanan, Wang Aiping
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, China.
Department of Thoracic Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.
Front Pharmacol. 2022 Apr 25;13:882678. doi: 10.3389/fphar.2022.882678. eCollection 2022.
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by progressive and irreversible loss of lung function. Clinically safe and efficacious drug treatments for IPF are lacking. Pirfenidone (an anti-inflammatory, antioxidant and anti-fibrotic small-molecule drug) is considered a promising treatment for IPF. Unfortunately, several disadvantages of pirfenidone caused by traditional administration (e.g., gastrointestinal reactions, short elimination half-life) hinder its implementation. We designed pirfenidone pH-sensitive liposomes (PSLs) to target the acidic microenvironment of IPF and act directly at the disease site through pulmonary administration. Pirfenidone was encapsulated in liposomes to extend its half-life, and modified with polyethylene glycol on the surface of liposomes to improve the permeability of the mucus layer in airways. , the cytotoxicity of pirfenidone PSLs to pulmonary fibroblasts was increased significantly at 48 h compared with that using pirfenidone. In a murine and rat model of bleomycin-induced pulmonary fibrosis, pirfenidone PSLs inhibited IPF development and increased PSL accumulation in the lungs compared with that using pirfenidone solution or phosphate-buffered saline. Pirfenidone PSLs had potentially fewer side effects and stronger lung targeting. These results suggest that pirfenidone PSLs are promising preparations for IPF treatment.
特发性肺纤维化（IPF）是一种间质性肺疾病，其特征是肺功能进行性且不可逆丧失。目前缺乏针对IPF的临床安全有效的药物治疗方法。吡非尼酮（一种抗炎、抗氧化和抗纤维化的小分子药物）被认为是一种有前景的IPF治疗药物。不幸的是，传统给药方式导致的吡非尼酮的几个缺点（如胃肠道反应、消除半衰期短）阻碍了其应用。我们设计了吡非尼酮pH敏感脂质体（PSLs），以靶向IPF的酸性微环境，并通过肺部给药直接作用于疾病部位。将吡非尼酮包裹在脂质体中以延长其半衰期，并在脂质体表面用聚乙二醇进行修饰，以提高气道黏液层的通透性。与使用吡非尼酮相比，吡非尼酮PSLs在48小时时对肺成纤维细胞的细胞毒性显著增加。在博莱霉素诱导的肺纤维化小鼠和大鼠模型中，与使用吡非尼酮溶液或磷酸盐缓冲盐水相比，吡非尼酮PSLs抑制了IPF的发展，并增加了PSLs在肺中的蓄积。吡非尼酮PSLs的副作用可能更少，且具有更强的肺靶向性。这些结果表明，吡非尼酮PSLs是有前景的IPF治疗制剂。
