A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Macrophage-Targeted Lung Delivery of Dexamethasone Improves Pulmonary Fibrosis Therapy via Regulating the Immune Microenvironment
Tekijät: Sang Xiaoqing, Wang Yuanyuan, Xue Zhifeng, Qi Dawei, Fan Gunwei, Tian Fei, Zhu Yan, Yang Jian
Julkaisuvuosi: 2021
Journal: Frontiers in Immunology
Tietokannassa oleva lehden nimi: Frontiers in immunology
Lehden akronyymi: Front Immunol
Vuosikerta: 12
Sivujen määrä: 12
ISSN: 1664-3224
eISSN: 1664-3224
DOI: https://doi.org/10.3389/fimmu.2021.613907
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/53032908
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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
