Engineering of Stimulus-Responsive Pirfenidone Liposomes for Pulmonary Delivery During Treatment of Idiopathic Pulmonary Fibrosis

Frontiers in Pharmacology

卷:13

Yingjian Song¹  Meishan Han²  Sha Liu²  Aiping Wang²  Xiaosu Zhu²  Yanan Lu²  Xiaoyan Lu²  Meixuan Liu²  Kaoxiang Sun²  Linyu Su² 

[1] Department of Thoracic Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China;

[2] 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;

关键词: pirfenidone;    idiopathic pulmonary fibrosis;    stimulus-responsive liposomes;    pulmonary administration;    permeability of the mucus layer;   

DOI  :  10.3389/fphar.2022.882678

来源: DOAJ

【 摘 要 】

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. In vitro, 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.

【 授权许可】

Unknown