Cargando…

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

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 consi...

Descripción completa

Detalles Bibliográficos
Autores principales: Han, Meishan, Song, Yingjian, Liu, Sha, Lu, Xiaoyan, Su, Linyu, Liu, Meixuan, Zhu, Xiaosu, Sun, Kaoxiang, Lu, Yanan, Wang, Aiping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081653/
https://www.ncbi.nlm.nih.gov/pubmed/35548360
http://dx.doi.org/10.3389/fphar.2022.882678
_version_ 1784703035215183872
author Han, Meishan
Song, Yingjian
Liu, Sha
Lu, Xiaoyan
Su, Linyu
Liu, Meixuan
Zhu, Xiaosu
Sun, Kaoxiang
Lu, Yanan
Wang, Aiping
author_facet Han, Meishan
Song, Yingjian
Liu, Sha
Lu, Xiaoyan
Su, Linyu
Liu, Meixuan
Zhu, Xiaosu
Sun, Kaoxiang
Lu, Yanan
Wang, Aiping
author_sort Han, Meishan
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9081653
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-90816532022-05-10 Engineering of Stimulus-Responsive Pirfenidone Liposomes for Pulmonary Delivery During Treatment of Idiopathic Pulmonary Fibrosis Han, Meishan Song, Yingjian Liu, Sha Lu, Xiaoyan Su, Linyu Liu, Meixuan Zhu, Xiaosu Sun, Kaoxiang Lu, Yanan Wang, Aiping Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2022-04-25 /pmc/articles/PMC9081653/ /pubmed/35548360 http://dx.doi.org/10.3389/fphar.2022.882678 Text en Copyright © 2022 Han, Song, Liu, Lu, Su, Liu, Zhu, Sun, Lu and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Han, Meishan
Song, Yingjian
Liu, Sha
Lu, Xiaoyan
Su, Linyu
Liu, Meixuan
Zhu, Xiaosu
Sun, Kaoxiang
Lu, Yanan
Wang, Aiping
Engineering of Stimulus-Responsive Pirfenidone Liposomes for Pulmonary Delivery During Treatment of Idiopathic Pulmonary Fibrosis
title Engineering of Stimulus-Responsive Pirfenidone Liposomes for Pulmonary Delivery During Treatment of Idiopathic Pulmonary Fibrosis
title_full Engineering of Stimulus-Responsive Pirfenidone Liposomes for Pulmonary Delivery During Treatment of Idiopathic Pulmonary Fibrosis
title_fullStr Engineering of Stimulus-Responsive Pirfenidone Liposomes for Pulmonary Delivery During Treatment of Idiopathic Pulmonary Fibrosis
title_full_unstemmed Engineering of Stimulus-Responsive Pirfenidone Liposomes for Pulmonary Delivery During Treatment of Idiopathic Pulmonary Fibrosis
title_short Engineering of Stimulus-Responsive Pirfenidone Liposomes for Pulmonary Delivery During Treatment of Idiopathic Pulmonary Fibrosis
title_sort engineering of stimulus-responsive pirfenidone liposomes for pulmonary delivery during treatment of idiopathic pulmonary fibrosis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081653/
https://www.ncbi.nlm.nih.gov/pubmed/35548360
http://dx.doi.org/10.3389/fphar.2022.882678
work_keys_str_mv AT hanmeishan engineeringofstimulusresponsivepirfenidoneliposomesforpulmonarydeliveryduringtreatmentofidiopathicpulmonaryfibrosis
AT songyingjian engineeringofstimulusresponsivepirfenidoneliposomesforpulmonarydeliveryduringtreatmentofidiopathicpulmonaryfibrosis
AT liusha engineeringofstimulusresponsivepirfenidoneliposomesforpulmonarydeliveryduringtreatmentofidiopathicpulmonaryfibrosis
AT luxiaoyan engineeringofstimulusresponsivepirfenidoneliposomesforpulmonarydeliveryduringtreatmentofidiopathicpulmonaryfibrosis
AT sulinyu engineeringofstimulusresponsivepirfenidoneliposomesforpulmonarydeliveryduringtreatmentofidiopathicpulmonaryfibrosis
AT liumeixuan engineeringofstimulusresponsivepirfenidoneliposomesforpulmonarydeliveryduringtreatmentofidiopathicpulmonaryfibrosis
AT zhuxiaosu engineeringofstimulusresponsivepirfenidoneliposomesforpulmonarydeliveryduringtreatmentofidiopathicpulmonaryfibrosis
AT sunkaoxiang engineeringofstimulusresponsivepirfenidoneliposomesforpulmonarydeliveryduringtreatmentofidiopathicpulmonaryfibrosis
AT luyanan engineeringofstimulusresponsivepirfenidoneliposomesforpulmonarydeliveryduringtreatmentofidiopathicpulmonaryfibrosis
AT wangaiping engineeringofstimulusresponsivepirfenidoneliposomesforpulmonarydeliveryduringtreatmentofidiopathicpulmonaryfibrosis