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Macrophage-Targeted Lung Delivery of Dexamethasone Improves Pulmonary Fibrosis Therapy via Regulating the Immune Microenvironment

Idiopathic pulmonary fibrosis (IPF) is serious chronic lung disease with limited therapeutic approaches. Inflammation and immune disorders are considered as the main factors in the initiation and development of pulmonary fibrosis. Inspired by the key roles of macrophages during the processes of infl...

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Autores principales: Sang, Xiaoqing, Wang, Yuanyuan, Xue, Zhifeng, Qi, Dawei, Fan, Guanwei, Tian, Fei, Zhu, Yan, Yang, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935565/
https://www.ncbi.nlm.nih.gov/pubmed/33679754
http://dx.doi.org/10.3389/fimmu.2021.613907
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author Sang, Xiaoqing
Wang, Yuanyuan
Xue, Zhifeng
Qi, Dawei
Fan, Guanwei
Tian, Fei
Zhu, Yan
Yang, Jian
author_facet Sang, Xiaoqing
Wang, Yuanyuan
Xue, Zhifeng
Qi, Dawei
Fan, Guanwei
Tian, Fei
Zhu, Yan
Yang, Jian
author_sort Sang, Xiaoqing
collection PubMed
description Idiopathic pulmonary fibrosis (IPF) is serious chronic lung disease with limited therapeutic approaches. Inflammation and immune disorders are considered as the main factors in the initiation and development of pulmonary fibrosis. Inspired by the key roles of macrophages during the processes of inflammation and immune disorders, here, we report a new method for direct drug delivery into the in-situ fibrotic tissue sites in vitro and in vivo. First, liposomes containing dexamethasone (Dex-L) are prepared and designed to entry into the macrophages in the early hours, forming the macrophages loaded Dex-L delivery system (Dex-L-MV). Chemokine and cytokine factors such as IL-6, IL-10, Arg-1 are measured to show the effect of Dex-L to the various subtypes of macrophages. Next, we mimic the inflammatory and anti-inflammatory microenvironment by co-culture of polarized/inactive macrophage and fibroblast cells to show the acute inflammation response of Dex-L-MV. Further, we confirm the targeted delivery of Dex-L-MV into the inflammatory sites in vivo, and surprisingly found that injected macrophage containing Dex can reduce the level of macrophage infiltration and expression of the markers of collagen deposition during the fibrotic stage, while causing little systematic toxicity. These data demonstrated the suitability and immune regulation effect of Dex-L-MV for the anti-pulmonary process. It is envisaged that these findings are a step forward toward endogenous immune targeting systems as a tool for clinical drug delivery.
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spelling pubmed-79355652021-03-06 Macrophage-Targeted Lung Delivery of Dexamethasone Improves Pulmonary Fibrosis Therapy via Regulating the Immune Microenvironment Sang, Xiaoqing Wang, Yuanyuan Xue, Zhifeng Qi, Dawei Fan, Guanwei Tian, Fei Zhu, Yan Yang, Jian Front Immunol Immunology Idiopathic pulmonary fibrosis (IPF) is serious chronic lung disease with limited therapeutic approaches. Inflammation and immune disorders are considered as the main factors in the initiation and development of pulmonary fibrosis. Inspired by the key roles of macrophages during the processes of inflammation and immune disorders, here, we report a new method for direct drug delivery into the in-situ fibrotic tissue sites in vitro and in vivo. First, liposomes containing dexamethasone (Dex-L) are prepared and designed to entry into the macrophages in the early hours, forming the macrophages loaded Dex-L delivery system (Dex-L-MV). Chemokine and cytokine factors such as IL-6, IL-10, Arg-1 are measured to show the effect of Dex-L to the various subtypes of macrophages. Next, we mimic the inflammatory and anti-inflammatory microenvironment by co-culture of polarized/inactive macrophage and fibroblast cells to show the acute inflammation response of Dex-L-MV. Further, we confirm the targeted delivery of Dex-L-MV into the inflammatory sites in vivo, and surprisingly found that injected macrophage containing Dex can reduce the level of macrophage infiltration and expression of the markers of collagen deposition during the fibrotic stage, while causing little systematic toxicity. These data demonstrated the suitability and immune regulation effect of Dex-L-MV for the anti-pulmonary process. It is envisaged that these findings are a step forward toward endogenous immune targeting systems as a tool for clinical drug delivery. Frontiers Media S.A. 2021-02-18 /pmc/articles/PMC7935565/ /pubmed/33679754 http://dx.doi.org/10.3389/fimmu.2021.613907 Text en Copyright © 2021 Sang, Wang, Xue, Qi, Fan, Tian, Zhu and Yang. http://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 Immunology
Sang, Xiaoqing
Wang, Yuanyuan
Xue, Zhifeng
Qi, Dawei
Fan, Guanwei
Tian, Fei
Zhu, Yan
Yang, Jian
Macrophage-Targeted Lung Delivery of Dexamethasone Improves Pulmonary Fibrosis Therapy via Regulating the Immune Microenvironment
title Macrophage-Targeted Lung Delivery of Dexamethasone Improves Pulmonary Fibrosis Therapy via Regulating the Immune Microenvironment
title_full Macrophage-Targeted Lung Delivery of Dexamethasone Improves Pulmonary Fibrosis Therapy via Regulating the Immune Microenvironment
title_fullStr Macrophage-Targeted Lung Delivery of Dexamethasone Improves Pulmonary Fibrosis Therapy via Regulating the Immune Microenvironment
title_full_unstemmed Macrophage-Targeted Lung Delivery of Dexamethasone Improves Pulmonary Fibrosis Therapy via Regulating the Immune Microenvironment
title_short Macrophage-Targeted Lung Delivery of Dexamethasone Improves Pulmonary Fibrosis Therapy via Regulating the Immune Microenvironment
title_sort macrophage-targeted lung delivery of dexamethasone improves pulmonary fibrosis therapy via regulating the immune microenvironment
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935565/
https://www.ncbi.nlm.nih.gov/pubmed/33679754
http://dx.doi.org/10.3389/fimmu.2021.613907
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