Inflammatory monocyte/macrophage modulation by liposome-entrapped spironolactone ameliorates acute lung injury in mice

Wen Jie Ji; Yong Qiang Ma; Xin Zhang; Li Zhang; Yi Dan Zhang; Cheng Cheng Su; Guo An Xiang; Mei Ping Zhang; Zhi Chun Lin; Lu Qing Wei; Peizhong P. Wang; Zhuoli Zhang; Yu Ming Li; Xin Zhou

doi:10.2217/nnm-2016-0006

Inflammatory monocyte/macrophage modulation by liposome-entrapped spironolactone ameliorates acute lung injury in mice

Wen Jie Ji, Yong Qiang Ma, Xin Zhang, Li Zhang, Yi Dan Zhang, Cheng Cheng Su, Guo An Xiang, Mei Ping Zhang, Zhi Chun Lin, Lu Qing Wei, Peizhong P. Wang, Zhuoli Zhang, Yu Ming Li^*, Xin Zhou

^*Corresponding author for this work

Radiology

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

Aim: To examine the therapeutic/preventive potential of liposome-encapsulated spironolactone (SP; Lipo-SP) for acute lung injury (ALI) and fibrosis. Materials & methods: Lipo-SP was prepared by the film-ultrasonic method, and physicochemical and pharmacokinetic characterized for oral administration (10 and 20 mg/kg for SP-loaded liposome; 20 mg/kg for free SP) in a mouse model bleomycin-induced ALI. Results: Lipo-SP enhanced bioavailability of SP with significant amelioration in lung pathology. Mechanistically, SP-mediated mineralocorticoid receptor antagonism contributes to inflammatory monocyte/macrophage modulation via an inhibitory effect on Ly6C^hi monocytosis-directed M2 polarization of alveolar macrophages. Moreover, Lipo-SP at lower dose (10 mg/kg) exhibited more improvement in body weight gain. Conclusion: Our data highlight Lipo-SP as a promising approach with therapeutic/preventive potential for ALI and fibrosis.

Original language	English (US)
Pages (from-to)	1393-1406
Number of pages	14
Journal	Nanomedicine
Volume	11
Issue number	11
DOIs	https://doi.org/10.2217/nnm-2016-0006
State	Published - Jun 2016

Funding

This work was supported by National Natural Science Foundation of China (81102088, 81170238, 81441101 and 81570335)

Keywords

acute lung injury
liposome
pulmonary fibrosis
spironolactone

ASJC Scopus subject areas

Bioengineering
Biomedical Engineering
General Materials Science
Medicine (miscellaneous)

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title = "Inflammatory monocyte/macrophage modulation by liposome-entrapped spironolactone ameliorates acute lung injury in mice",

abstract = "Aim: To examine the therapeutic/preventive potential of liposome-encapsulated spironolactone (SP; Lipo-SP) for acute lung injury (ALI) and fibrosis. Materials & methods: Lipo-SP was prepared by the film-ultrasonic method, and physicochemical and pharmacokinetic characterized for oral administration (10 and 20 mg/kg for SP-loaded liposome; 20 mg/kg for free SP) in a mouse model bleomycin-induced ALI. Results: Lipo-SP enhanced bioavailability of SP with significant amelioration in lung pathology. Mechanistically, SP-mediated mineralocorticoid receptor antagonism contributes to inflammatory monocyte/macrophage modulation via an inhibitory effect on Ly6Chi monocytosis-directed M2 polarization of alveolar macrophages. Moreover, Lipo-SP at lower dose (10 mg/kg) exhibited more improvement in body weight gain. Conclusion: Our data highlight Lipo-SP as a promising approach with therapeutic/preventive potential for ALI and fibrosis.",

keywords = "acute lung injury, liposome, pulmonary fibrosis, spironolactone",

author = "Ji, {Wen Jie} and Ma, {Yong Qiang} and Xin Zhang and Li Zhang and Zhang, {Yi Dan} and Su, {Cheng Cheng} and Xiang, {Guo An} and Zhang, {Mei Ping} and Lin, {Zhi Chun} and Wei, {Lu Qing} and Wang, {Peizhong P.} and Zhuoli Zhang and Li, {Yu Ming} and Xin Zhou",

note = "Publisher Copyright: {\textcopyright} 2016 Future Medicine Ltd.",

year = "2016",

month = jun,

doi = "10.2217/nnm-2016-0006",

language = "English (US)",

volume = "11",

pages = "1393--1406",

journal = "Nanomedicine",

issn = "1743-5889",

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AU - Ji, Wen Jie

AU - Ma, Yong Qiang

AU - Zhang, Xin

AU - Zhang, Li

AU - Zhang, Yi Dan

AU - Su, Cheng Cheng

AU - Xiang, Guo An

AU - Zhang, Mei Ping

AU - Lin, Zhi Chun

AU - Wei, Lu Qing

AU - Wang, Peizhong P.

AU - Zhang, Zhuoli

AU - Li, Yu Ming

AU - Zhou, Xin

PY - 2016/6

Y1 - 2016/6

N2 - Aim: To examine the therapeutic/preventive potential of liposome-encapsulated spironolactone (SP; Lipo-SP) for acute lung injury (ALI) and fibrosis. Materials & methods: Lipo-SP was prepared by the film-ultrasonic method, and physicochemical and pharmacokinetic characterized for oral administration (10 and 20 mg/kg for SP-loaded liposome; 20 mg/kg for free SP) in a mouse model bleomycin-induced ALI. Results: Lipo-SP enhanced bioavailability of SP with significant amelioration in lung pathology. Mechanistically, SP-mediated mineralocorticoid receptor antagonism contributes to inflammatory monocyte/macrophage modulation via an inhibitory effect on Ly6Chi monocytosis-directed M2 polarization of alveolar macrophages. Moreover, Lipo-SP at lower dose (10 mg/kg) exhibited more improvement in body weight gain. Conclusion: Our data highlight Lipo-SP as a promising approach with therapeutic/preventive potential for ALI and fibrosis.

AB - Aim: To examine the therapeutic/preventive potential of liposome-encapsulated spironolactone (SP; Lipo-SP) for acute lung injury (ALI) and fibrosis. Materials & methods: Lipo-SP was prepared by the film-ultrasonic method, and physicochemical and pharmacokinetic characterized for oral administration (10 and 20 mg/kg for SP-loaded liposome; 20 mg/kg for free SP) in a mouse model bleomycin-induced ALI. Results: Lipo-SP enhanced bioavailability of SP with significant amelioration in lung pathology. Mechanistically, SP-mediated mineralocorticoid receptor antagonism contributes to inflammatory monocyte/macrophage modulation via an inhibitory effect on Ly6Chi monocytosis-directed M2 polarization of alveolar macrophages. Moreover, Lipo-SP at lower dose (10 mg/kg) exhibited more improvement in body weight gain. Conclusion: Our data highlight Lipo-SP as a promising approach with therapeutic/preventive potential for ALI and fibrosis.

KW - acute lung injury

KW - liposome

KW - pulmonary fibrosis

KW - spironolactone

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Inflammatory monocyte/macrophage modulation by liposome-entrapped spironolactone ameliorates acute lung injury in mice

Abstract

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