LPS adsorption and inflammation alleviation by polymyxin B-modified liposomes for atherosclerosis treatment

Chronic inflammation is critical in the onset and progression of atherosclerosis (AS). The lipopolysaccharide (LPS) level in the circulation system is elevated in AS patients and animal models, which is correlated with the severity of AS. Inspired by the underlying mechanism that LPS could drive the...

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Main Authors: Huiwen Liu, Honglan Wang, Qiyu Li, Yiwei Wang, Ying He, Xuejing Li, Chunyan Sun, Onder Ergonul, Füsun Can, Zhiqing Pang, Bo Zhang, Yu Hu
Format: Article
Language:English
Published: Elsevier 2023-09-01
Series:Acta Pharmaceutica Sinica B
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211383523002083
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author Huiwen Liu
Honglan Wang
Qiyu Li
Yiwei Wang
Ying He
Xuejing Li
Chunyan Sun
Onder Ergonul
Füsun Can
Zhiqing Pang
Bo Zhang
Yu Hu
author_facet Huiwen Liu
Honglan Wang
Qiyu Li
Yiwei Wang
Ying He
Xuejing Li
Chunyan Sun
Onder Ergonul
Füsun Can
Zhiqing Pang
Bo Zhang
Yu Hu
author_sort Huiwen Liu
collection DOAJ
description Chronic inflammation is critical in the onset and progression of atherosclerosis (AS). The lipopolysaccharide (LPS) level in the circulation system is elevated in AS patients and animal models, which is correlated with the severity of AS. Inspired by the underlying mechanism that LPS could drive the polarization of macrophages toward the M1 phenotype, aggravate inflammation, and ultimately contribute to the exacerbation of AS, LPS in the circulation system was supposed to be the therapeutic target for AS treatment. In the present study, polymyxin (PMB) covalently conjugated to PEGylated liposomes (PLPs) were formulated to adsorb LPS through specific interactions between PMB and LPS. In vitro, the experiments demonstrated that PLPs could adsorb LPS, reduce the polarization of macrophages to M1 phenotype and inhibit the formation of foam cells. In vivo, the study revealed that PLPs treatment reduced the serum levels of LPS and pro-inflammatory cytokines, decreased the proportion of M1-type macrophages in AS plaque, stabilized AS plaque, and downsized the plaque burdens in arteries, which eventually attenuated the progression of AS. Our study highlighted LPS in the circulation system as the therapeutic target for AS and provided an alternative strategy for AS treatment.
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spelling doaj.art-64fee4360e1b4fb58c741ab3e3c6e46d2023-09-08T04:33:20ZengElsevierActa Pharmaceutica Sinica B2211-38352023-09-0113938173833LPS adsorption and inflammation alleviation by polymyxin B-modified liposomes for atherosclerosis treatmentHuiwen Liu0Honglan Wang1Qiyu Li2Yiwei Wang3Ying He4Xuejing Li5Chunyan Sun6Onder Ergonul7Füsun Can8Zhiqing Pang9Bo Zhang10Yu Hu11Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430022, ChinaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430022, ChinaDepartment of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, ChinaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430022, ChinaSchool of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, ChinaSchool of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, ChinaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430022, ChinaKoç University Iş Bank Center for Infectious Diseases (KUISCID), Lnfectious Diseases and Clinical Microbiology Department, Koç University School of Medicine and American Hospital, Istanbul 34010, TurkeyKoç University Iş Bank Center for Infectious Diseases (KUISCID), Lnfectious Diseases and Clinical Microbiology Department, Koç University School of Medicine and American Hospital, Istanbul 34010, TurkeySchool of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, China; Corresponding authors.Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430022, China; Corresponding authors.Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430022, China; Corresponding authors.Chronic inflammation is critical in the onset and progression of atherosclerosis (AS). The lipopolysaccharide (LPS) level in the circulation system is elevated in AS patients and animal models, which is correlated with the severity of AS. Inspired by the underlying mechanism that LPS could drive the polarization of macrophages toward the M1 phenotype, aggravate inflammation, and ultimately contribute to the exacerbation of AS, LPS in the circulation system was supposed to be the therapeutic target for AS treatment. In the present study, polymyxin (PMB) covalently conjugated to PEGylated liposomes (PLPs) were formulated to adsorb LPS through specific interactions between PMB and LPS. In vitro, the experiments demonstrated that PLPs could adsorb LPS, reduce the polarization of macrophages to M1 phenotype and inhibit the formation of foam cells. In vivo, the study revealed that PLPs treatment reduced the serum levels of LPS and pro-inflammatory cytokines, decreased the proportion of M1-type macrophages in AS plaque, stabilized AS plaque, and downsized the plaque burdens in arteries, which eventually attenuated the progression of AS. Our study highlighted LPS in the circulation system as the therapeutic target for AS and provided an alternative strategy for AS treatment.http://www.sciencedirect.com/science/article/pii/S2211383523002083LipopolysaccharideAtherosclerosisPolymyxinLiposomesMacrophages
spellingShingle Huiwen Liu
Honglan Wang
Qiyu Li
Yiwei Wang
Ying He
Xuejing Li
Chunyan Sun
Onder Ergonul
Füsun Can
Zhiqing Pang
Bo Zhang
Yu Hu
LPS adsorption and inflammation alleviation by polymyxin B-modified liposomes for atherosclerosis treatment
Acta Pharmaceutica Sinica B
Lipopolysaccharide
Atherosclerosis
Polymyxin
Liposomes
Macrophages
title LPS adsorption and inflammation alleviation by polymyxin B-modified liposomes for atherosclerosis treatment
title_full LPS adsorption and inflammation alleviation by polymyxin B-modified liposomes for atherosclerosis treatment
title_fullStr LPS adsorption and inflammation alleviation by polymyxin B-modified liposomes for atherosclerosis treatment
title_full_unstemmed LPS adsorption and inflammation alleviation by polymyxin B-modified liposomes for atherosclerosis treatment
title_short LPS adsorption and inflammation alleviation by polymyxin B-modified liposomes for atherosclerosis treatment
title_sort lps adsorption and inflammation alleviation by polymyxin b modified liposomes for atherosclerosis treatment
topic Lipopolysaccharide
Atherosclerosis
Polymyxin
Liposomes
Macrophages
url http://www.sciencedirect.com/science/article/pii/S2211383523002083
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