Novel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant Staphylococcus aureus

Novel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant Staphylococcus aureus

Xiaowei Liu,1,* Zhan Li,1,* Xiaodong Wang,2,3 Yujuan Chen,2,3 Fengbo Wu,2,3 Ke Men,1 Ting Xu,2,3 Yan Luo,1 Li Yang1 1State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, 2Department of Thyroid and Breast Surgery, 3Department of Pharmacy, West China Hospital, Sichuan Un...

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Autores principales: Liu X, Li Z, Wang X, Chen Y, Wu F, Men K, Xu T, Luo Y, Yang L
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2016
Materias:
DP7-C
azithromycin
antimicrobial resistance
antimicrobial peptides
liposome
immune-regulation
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/779b2e509e264dd28332ce869ea6d5de
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spelling oai:doaj.org-article:779b2e509e264dd28332ce869ea6d5de2021-12-02T05:10:43ZNovel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant Staphylococcus aureus1178-2013https://doaj.org/article/779b2e509e264dd28332ce869ea6d5de2016-12-01T00:00:00Zhttps://www.dovepress.com/novel-antimicrobial-peptidendashmodified--azithromycin-loaded-liposome-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiaowei Liu,1,* Zhan Li,1,* Xiaodong Wang,2,3 Yujuan Chen,2,3 Fengbo Wu,2,3 Ke Men,1 Ting Xu,2,3 Yan Luo,1 Li Yang1 1State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, 2Department of Thyroid and Breast Surgery, 3Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China *These authors contributed equally to this work Abstract: Infections caused by multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), have become a public threat; therefore, development of new antimicrobial drugs or strategies is urgently required. In this study, a new antibacterial peptide DP7-C (Chol-suc-VQWRIRVAVIRK-NH2) and DP7-C-modified azithromycin (AZT)-loaded liposomes (LPs) are developed for the treatment of MRSA infection, and it was found that DP7-C inserted into the LP lipid bilayer not only functioned as a carrier to encapsulate the antibiotic AZT but also synergized the antibacterial effect of the encapsulated AZT. In vitro assays showed that DP7-C-modified LPs possessed sustained drug release profile and immune regulatory effect and did not show obvious cytotoxicity in mammal cells, but they did not possess direct antibacterial activity in vitro. In vivo studies revealed that DP7-C-modified LPs did not exhibit obvious side effects or toxicity in mice but were able to significantly reduce the bacterial counts in an MRSA-infectious mouse model and possessed high antibacterial activity. In particular, DP7-C-modified AZT-loaded LPs showed more positive therapeutic effects than either DP7-C-modified blank LPs or nonmodified AZT-loaded LPs treatment alone. Molecular mechanism studies demonstrated that DP7-C formulations effectively upregulated the production of anti-inflammatory cytokines and chemokines without inducing harmful immune response, suggesting that DP7-C was synergistic with AZT against the bacterial infection by activating the innate immune response. Most importantly, although DP7-C activated the innate immune response, it did not possess direct antibacterial activity in vitro, indicating that DP7-C did not possess the potential to induce bacteria resistance. The findings indicate that DP7-C-modified AZT-loaded LPs developed in this study have a great potential required for the clinical treatment of MRSA infections. Keywords: DP7-C, azithromycin, antimicrobial resistance, MRSA infections, immune-regulationLiu XLi ZWang XChen YWu FMen KXu TLuo YYang LDove Medical PressarticleDP7-Cazithromycinantimicrobial resistanceantimicrobial peptidesliposomeimmune-regulationMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 6781-6794 (2016)
institution DOAJ
collection DOAJ
language EN
topic DP7-C
azithromycin
antimicrobial resistance
antimicrobial peptides
liposome
immune-regulation
Medicine (General)
R5-920
spellingShingle DP7-C
azithromycin
antimicrobial resistance
antimicrobial peptides
liposome
immune-regulation
Medicine (General)
R5-920
Liu X
Li Z
Wang X
Chen Y
Wu F
Men K
Xu T
Luo Y
Yang L
Novel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant Staphylococcus aureus
description Xiaowei Liu,1,* Zhan Li,1,* Xiaodong Wang,2,3 Yujuan Chen,2,3 Fengbo Wu,2,3 Ke Men,1 Ting Xu,2,3 Yan Luo,1 Li Yang1 1State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, 2Department of Thyroid and Breast Surgery, 3Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China *These authors contributed equally to this work Abstract: Infections caused by multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), have become a public threat; therefore, development of new antimicrobial drugs or strategies is urgently required. In this study, a new antibacterial peptide DP7-C (Chol-suc-VQWRIRVAVIRK-NH2) and DP7-C-modified azithromycin (AZT)-loaded liposomes (LPs) are developed for the treatment of MRSA infection, and it was found that DP7-C inserted into the LP lipid bilayer not only functioned as a carrier to encapsulate the antibiotic AZT but also synergized the antibacterial effect of the encapsulated AZT. In vitro assays showed that DP7-C-modified LPs possessed sustained drug release profile and immune regulatory effect and did not show obvious cytotoxicity in mammal cells, but they did not possess direct antibacterial activity in vitro. In vivo studies revealed that DP7-C-modified LPs did not exhibit obvious side effects or toxicity in mice but were able to significantly reduce the bacterial counts in an MRSA-infectious mouse model and possessed high antibacterial activity. In particular, DP7-C-modified AZT-loaded LPs showed more positive therapeutic effects than either DP7-C-modified blank LPs or nonmodified AZT-loaded LPs treatment alone. Molecular mechanism studies demonstrated that DP7-C formulations effectively upregulated the production of anti-inflammatory cytokines and chemokines without inducing harmful immune response, suggesting that DP7-C was synergistic with AZT against the bacterial infection by activating the innate immune response. Most importantly, although DP7-C activated the innate immune response, it did not possess direct antibacterial activity in vitro, indicating that DP7-C did not possess the potential to induce bacteria resistance. The findings indicate that DP7-C-modified AZT-loaded LPs developed in this study have a great potential required for the clinical treatment of MRSA infections. Keywords: DP7-C, azithromycin, antimicrobial resistance, MRSA infections, immune-regulation
format article
author Liu X
Li Z
Wang X
Chen Y
Wu F
Men K
Xu T
Luo Y
Yang L
author_facet Liu X
Li Z
Wang X
Chen Y
Wu F
Men K
Xu T
Luo Y
Yang L
author_sort Liu X
title Novel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant Staphylococcus aureus
title_short Novel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant Staphylococcus aureus
title_full Novel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant Staphylococcus aureus
title_fullStr Novel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant Staphylococcus aureus
title_full_unstemmed Novel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant Staphylococcus aureus
title_sort novel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant staphylococcus aureus
publisher Dove Medical Press
publishDate 2016
url https://doaj.org/article/779b2e509e264dd28332ce869ea6d5de
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