Synergistic antibacterial effect of ultrasound microbubbles combined with chitosan-modified polymyxin B-loaded liposomes on biofilm-producing Acinetobacter baumannii

Yu-Ying Fu,1 Liang Zhang,2 Yi Yang,1 Cheng-Wei Liu,3 Ying-Na He,4 Pan Li,2 Xian Yu1 1Phase I Clinical Trial Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; 2Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, Second Af...

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Autores principales:	Fu Y, Zhang L, Yang Y, Liu C, He Y, Li P, Yu X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	liposome chitosan polymyxin B ultrasound microbubbles Acinetobacter baumannii bio-films Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b288a687e17048d1b7b19e71be684a55
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spelling	oai:doaj.org-article:b288a687e17048d1b7b19e71be684a552021-12-02T03:42:08ZSynergistic antibacterial effect of ultrasound microbubbles combined with chitosan-modified polymyxin B-loaded liposomes on biofilm-producing Acinetobacter baumannii1178-2013https://doaj.org/article/b288a687e17048d1b7b19e71be684a552019-03-01T00:00:00Zhttps://www.dovepress.com/synergistic-antibacterial-effect-of-ultrasound-microbubbles-combined-w-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yu-Ying Fu,1 Liang Zhang,2 Yi Yang,1 Cheng-Wei Liu,3 Ying-Na He,4 Pan Li,2 Xian Yu1 1Phase I Clinical Trial Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; 2Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China; 3State Key Laboratory of Infectious Diseases and Parasites, First Affiliated Hospital, Chongqing Medical University, Chongqing, China; 4Department of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, China Purpose: Resistant strains of Acinetobacter baumannii (AB) that can form biofilms are resistant to polymyxin. Therefore, effective and safe polymyxin preparations against biofilm-producing AB are urgently needed. This study aims to prepare chitosan-modified polymyxin B-loaded liposomes (CLPs) and ultrasound microbubbles (USMBs) and then explore the synergistic antibacterial effects of USMBs combined with CLPs in vitro.Methods: CLPs were prepared using a modified injection method, and microbubbles were prepared using a simple mechanical vibration method. Minimal biofilm inhibitory concentration (MBIC) of CLPs against resistant biofilm-producing AB was determined. Antibacterial activities of CLPs with or without USMBs were analyzed by crystal violet staining and resazurin assays to evaluate biofilm mass and viable counts, respectively. Then, the anti-biofilm effects of CLPs with or without USMBs on biofilm-producing AB were confirmed via scanning electron microscopy (SEM) analysis.Results: We prepared CLPs that were 225.17±17.85 nm in size and carried positive charges of 12.64±1.44 mV. These CLPs, with higher encapsulation efficiency and drug loading, could exhibit a sustained release effect. We prepared microbubbles that were 2.391±0.052 µm in size and carried negative charges of -4.32±0.43 mV. The MBICs of the CLPs on the biofilm-producing AB was 8±2 µg/mL, while that of polymyxin B was 32±2 µg/mL. USMBs in combination with 2 µg/mL of polymyxin B could completely eliminate the biofilm-producing AB and achieve the maximum antimicrobial effects (P>0.05 vs sterile blank control). SEM imaging revealed some scattered bacteria without a biofilm structure in the USMB combined with the CLP group, confirming that this combination has the greatest anti-biofilm effects.Conclusion: In this research, we successfully prepared USMBs and CLPs that have a more significant antibacterial effect on biofilm-forming AB than polymyxin B alone. Experiments in vitro indicate that the synergistic antibacterial effect of combining USMBs with CLPs containing as little as 2 µg/mL of polymyxin B is sufficient to almost eliminate drug-resistant biofilm-producing AB. Keywords: liposome, chitosan, polymyxin B, ultrasound microbubbles, Acinetobacter baumannii, biofilmsFu YZhang LYang YLiu CHe YLi PYu XDove Medical Pressarticleliposomechitosanpolymyxin Bultrasound microbubblesAcinetobacter baumanniibio-filmsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 1805-1815 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	liposome chitosan polymyxin B ultrasound microbubbles Acinetobacter baumannii bio-films Medicine (General) R5-920
spellingShingle	liposome chitosan polymyxin B ultrasound microbubbles Acinetobacter baumannii bio-films Medicine (General) R5-920 Fu Y Zhang L Yang Y Liu C He Y Li P Yu X Synergistic antibacterial effect of ultrasound microbubbles combined with chitosan-modified polymyxin B-loaded liposomes on biofilm-producing Acinetobacter baumannii
description	Yu-Ying Fu,1 Liang Zhang,2 Yi Yang,1 Cheng-Wei Liu,3 Ying-Na He,4 Pan Li,2 Xian Yu1 1Phase I Clinical Trial Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; 2Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China; 3State Key Laboratory of Infectious Diseases and Parasites, First Affiliated Hospital, Chongqing Medical University, Chongqing, China; 4Department of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, China Purpose: Resistant strains of Acinetobacter baumannii (AB) that can form biofilms are resistant to polymyxin. Therefore, effective and safe polymyxin preparations against biofilm-producing AB are urgently needed. This study aims to prepare chitosan-modified polymyxin B-loaded liposomes (CLPs) and ultrasound microbubbles (USMBs) and then explore the synergistic antibacterial effects of USMBs combined with CLPs in vitro.Methods: CLPs were prepared using a modified injection method, and microbubbles were prepared using a simple mechanical vibration method. Minimal biofilm inhibitory concentration (MBIC) of CLPs against resistant biofilm-producing AB was determined. Antibacterial activities of CLPs with or without USMBs were analyzed by crystal violet staining and resazurin assays to evaluate biofilm mass and viable counts, respectively. Then, the anti-biofilm effects of CLPs with or without USMBs on biofilm-producing AB were confirmed via scanning electron microscopy (SEM) analysis.Results: We prepared CLPs that were 225.17±17.85 nm in size and carried positive charges of 12.64±1.44 mV. These CLPs, with higher encapsulation efficiency and drug loading, could exhibit a sustained release effect. We prepared microbubbles that were 2.391±0.052 µm in size and carried negative charges of -4.32±0.43 mV. The MBICs of the CLPs on the biofilm-producing AB was 8±2 µg/mL, while that of polymyxin B was 32±2 µg/mL. USMBs in combination with 2 µg/mL of polymyxin B could completely eliminate the biofilm-producing AB and achieve the maximum antimicrobial effects (P>0.05 vs sterile blank control). SEM imaging revealed some scattered bacteria without a biofilm structure in the USMB combined with the CLP group, confirming that this combination has the greatest anti-biofilm effects.Conclusion: In this research, we successfully prepared USMBs and CLPs that have a more significant antibacterial effect on biofilm-forming AB than polymyxin B alone. Experiments in vitro indicate that the synergistic antibacterial effect of combining USMBs with CLPs containing as little as 2 µg/mL of polymyxin B is sufficient to almost eliminate drug-resistant biofilm-producing AB. Keywords: liposome, chitosan, polymyxin B, ultrasound microbubbles, Acinetobacter baumannii, biofilms
format	article
author	Fu Y Zhang L Yang Y Liu C He Y Li P Yu X
author_facet	Fu Y Zhang L Yang Y Liu C He Y Li P Yu X
author_sort	Fu Y
title	Synergistic antibacterial effect of ultrasound microbubbles combined with chitosan-modified polymyxin B-loaded liposomes on biofilm-producing Acinetobacter baumannii
title_short	Synergistic antibacterial effect of ultrasound microbubbles combined with chitosan-modified polymyxin B-loaded liposomes on biofilm-producing Acinetobacter baumannii
title_full	Synergistic antibacterial effect of ultrasound microbubbles combined with chitosan-modified polymyxin B-loaded liposomes on biofilm-producing Acinetobacter baumannii
title_fullStr	Synergistic antibacterial effect of ultrasound microbubbles combined with chitosan-modified polymyxin B-loaded liposomes on biofilm-producing Acinetobacter baumannii
title_full_unstemmed	Synergistic antibacterial effect of ultrasound microbubbles combined with chitosan-modified polymyxin B-loaded liposomes on biofilm-producing Acinetobacter baumannii
title_sort	synergistic antibacterial effect of ultrasound microbubbles combined with chitosan-modified polymyxin b-loaded liposomes on biofilm-producing acinetobacter baumannii
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/b288a687e17048d1b7b19e71be684a55
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Synergistic antibacterial effect of ultrasound microbubbles combined with chitosan-modified polymyxin B-loaded liposomes on biofilm-producing Acinetobacter baumannii

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