Sinapultide-Loaded Microbubbles Combined with Ultrasound to Attenuate Lipopolysaccharide-Induced Acute Lung Injury in Mice

Dong Liu,1– 3 Yanjun Chen,1,2 Fang Li,1,2 Cunwu Chen,1,2 Peipei Wei,1,2 Deli Xiao,4,5 Bangxin Han1,2 1School of Biological and Pharmaceutical Engineering, West Anhui University, Lu’an 237012, People’s Republic of China; 2Anhui Engineering Laboratory for Conservation and...

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Main Authors: Liu D, Chen Y, Li F, Chen C, Wei P, Xiao D, Han B
Format: Article
Language:English
Published: Dove Medical Press 2020-12-01
Series:Drug Design, Development and Therapy
Subjects:
Online Access:https://www.dovepress.com/sinapultide-loaded-microbubbles-combined-with-ultrasound-to-attenuate--peer-reviewed-article-DDDT
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author Liu D
Chen Y
Li F
Chen C
Wei P
Xiao D
Han B
author_facet Liu D
Chen Y
Li F
Chen C
Wei P
Xiao D
Han B
author_sort Liu D
collection DOAJ
description Dong Liu,1– 3 Yanjun Chen,1,2 Fang Li,1,2 Cunwu Chen,1,2 Peipei Wei,1,2 Deli Xiao,4,5 Bangxin Han1,2 1School of Biological and Pharmaceutical Engineering, West Anhui University, Lu’an 237012, People’s Republic of China; 2Anhui Engineering Laboratory for Conservation and Sustainable Utilization of Traditional Chinese Medicine Resources, Lu’an 237012, People’s Republic of China; 3School of Biomedical Sciences and Medical Engineering, Southeast University, Nanjing 210009, People’s Republic of China; 4Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009, People’s Republic of China; 5Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing 210009, People’s Republic of ChinaCorrespondence: Deli XiaoDepartment of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009, People’s Republic of ChinaTel +86 25 86185160Email xiao49562001@163.comBangxin HanSchool of Biological and Pharmaceutical Engineering, West Anhui University, Lu’an 237012, People’s Republic of ChinaTel +86 564 3305073Email hanbx1978@sina.comPurpose: Pulmonary surfactants (eg, sinapultide) are widely used for the treatment of lung injury diseases; however, they generally induce poor therapeutic efficacy in clinics. In this study, sinapultide-loaded microbubbles (MBs) were prepared and combined with ultrasound (US) treatment as a new strategy for improved treatment of lung injury diseases.Methods: The combination treatment strategy of MBs combined with ultrasound was tested in a lipopolysaccharide (LPS)-induced mouse model of alveolar epithelial cells (AT II) and acute lung injury. Firstly, cytotoxicity, cytokines, and protein levels in LPS-mediated AT II cells were assessed. Secondly, the pathological morphology of lung tissue, the wet/dry (W/D) weight ratio, cytokines, and protein levels in LPS-mediated acute lung injury mice after treatment with the MBs were evaluated. Moreover, histology examination of the heart, liver, spleen, lung and kidney of mice treated with the MBs was performed to initially evaluate the safety of the sinapultide-loaded MBs.Results: Sinapultide-loaded MBs in combination with ultrasound treatment significantly reduced the secretion of inflammatory cytokines and increased the expression of surfactant protein A (SP-A) in AT II cells. Furthermore, the pathological morphology of lung tissue, the wet/dry (W/D) weight ratio, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and SP-A expression level of mice treated with MBs and ultrasound were significantly improved compared to those of non-treated mice. In addition, the histology of the examined organs showed that the MBs had a good safety profile.Conclusion: Sinapultide-loaded MBs combined with ultrasonic treatment may be a new therapeutic option for lung injury diseases in the clinic.Keywords: sinapultide, microbubbles, lipopolysaccharide, lung injury, safety
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spelling doaj.art-9f0fd9d9982d4cc790642b2c1450a9532022-12-21T20:34:40ZengDove Medical PressDrug Design, Development and Therapy1177-88812020-12-01Volume 145611562260556Sinapultide-Loaded Microbubbles Combined with Ultrasound to Attenuate Lipopolysaccharide-Induced Acute Lung Injury in MiceLiu DChen YLi FChen CWei PXiao DHan BDong Liu,1– 3 Yanjun Chen,1,2 Fang Li,1,2 Cunwu Chen,1,2 Peipei Wei,1,2 Deli Xiao,4,5 Bangxin Han1,2 1School of Biological and Pharmaceutical Engineering, West Anhui University, Lu’an 237012, People’s Republic of China; 2Anhui Engineering Laboratory for Conservation and Sustainable Utilization of Traditional Chinese Medicine Resources, Lu’an 237012, People’s Republic of China; 3School of Biomedical Sciences and Medical Engineering, Southeast University, Nanjing 210009, People’s Republic of China; 4Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009, People’s Republic of China; 5Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing 210009, People’s Republic of ChinaCorrespondence: Deli XiaoDepartment of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009, People’s Republic of ChinaTel +86 25 86185160Email xiao49562001@163.comBangxin HanSchool of Biological and Pharmaceutical Engineering, West Anhui University, Lu’an 237012, People’s Republic of ChinaTel +86 564 3305073Email hanbx1978@sina.comPurpose: Pulmonary surfactants (eg, sinapultide) are widely used for the treatment of lung injury diseases; however, they generally induce poor therapeutic efficacy in clinics. In this study, sinapultide-loaded microbubbles (MBs) were prepared and combined with ultrasound (US) treatment as a new strategy for improved treatment of lung injury diseases.Methods: The combination treatment strategy of MBs combined with ultrasound was tested in a lipopolysaccharide (LPS)-induced mouse model of alveolar epithelial cells (AT II) and acute lung injury. Firstly, cytotoxicity, cytokines, and protein levels in LPS-mediated AT II cells were assessed. Secondly, the pathological morphology of lung tissue, the wet/dry (W/D) weight ratio, cytokines, and protein levels in LPS-mediated acute lung injury mice after treatment with the MBs were evaluated. Moreover, histology examination of the heart, liver, spleen, lung and kidney of mice treated with the MBs was performed to initially evaluate the safety of the sinapultide-loaded MBs.Results: Sinapultide-loaded MBs in combination with ultrasound treatment significantly reduced the secretion of inflammatory cytokines and increased the expression of surfactant protein A (SP-A) in AT II cells. Furthermore, the pathological morphology of lung tissue, the wet/dry (W/D) weight ratio, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and SP-A expression level of mice treated with MBs and ultrasound were significantly improved compared to those of non-treated mice. In addition, the histology of the examined organs showed that the MBs had a good safety profile.Conclusion: Sinapultide-loaded MBs combined with ultrasonic treatment may be a new therapeutic option for lung injury diseases in the clinic.Keywords: sinapultide, microbubbles, lipopolysaccharide, lung injury, safetyhttps://www.dovepress.com/sinapultide-loaded-microbubbles-combined-with-ultrasound-to-attenuate--peer-reviewed-article-DDDTsinapultidemicrobubbleslipopolysaccharidelung injurysafety
spellingShingle Liu D
Chen Y
Li F
Chen C
Wei P
Xiao D
Han B
Sinapultide-Loaded Microbubbles Combined with Ultrasound to Attenuate Lipopolysaccharide-Induced Acute Lung Injury in Mice
Drug Design, Development and Therapy
sinapultide
microbubbles
lipopolysaccharide
lung injury
safety
title Sinapultide-Loaded Microbubbles Combined with Ultrasound to Attenuate Lipopolysaccharide-Induced Acute Lung Injury in Mice
title_full Sinapultide-Loaded Microbubbles Combined with Ultrasound to Attenuate Lipopolysaccharide-Induced Acute Lung Injury in Mice
title_fullStr Sinapultide-Loaded Microbubbles Combined with Ultrasound to Attenuate Lipopolysaccharide-Induced Acute Lung Injury in Mice
title_full_unstemmed Sinapultide-Loaded Microbubbles Combined with Ultrasound to Attenuate Lipopolysaccharide-Induced Acute Lung Injury in Mice
title_short Sinapultide-Loaded Microbubbles Combined with Ultrasound to Attenuate Lipopolysaccharide-Induced Acute Lung Injury in Mice
title_sort sinapultide loaded microbubbles combined with ultrasound to attenuate lipopolysaccharide induced acute lung injury in mice
topic sinapultide
microbubbles
lipopolysaccharide
lung injury
safety
url https://www.dovepress.com/sinapultide-loaded-microbubbles-combined-with-ultrasound-to-attenuate--peer-reviewed-article-DDDT
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AT lif sinapultideloadedmicrobubblescombinedwithultrasoundtoattenuatelipopolysaccharideinducedacutelunginjuryinmice
AT chenc sinapultideloadedmicrobubblescombinedwithultrasoundtoattenuatelipopolysaccharideinducedacutelunginjuryinmice
AT weip sinapultideloadedmicrobubblescombinedwithultrasoundtoattenuatelipopolysaccharideinducedacutelunginjuryinmice
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