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

Authors :
Meishan Han
Yingjian Song
Sha Liu
Xiaoyan Lu
Linyu Su
Meixuan Liu
Xiaosu Zhu
Kaoxiang Sun
Yanan Lu
Aiping Wang
Source :
Frontiers in Pharmacology, Vol 13 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

Abstract

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.

Details

Language :
English
ISSN :
16639812
Volume :
13
Database :
Directory of Open Access Journals
Journal :
Frontiers in Pharmacology
Publication Type :
Academic Journal
Accession number :
edsdoj.3ef4ab7e60484c11a85ab3ea3249f40f
Document Type :
article
Full Text :
https://doi.org/10.3389/fphar.2022.882678