Novel stable cytokine delivery system in physiological pH solution: chitosan oligosaccharide/heparin nanoparticles

Novel stable cytokine delivery system in physiological pH solution: chitosan oligosaccharide/heparin nanoparticles

Bin Wang, Ling Tan, Dengpu Deng, Ting Lu, Changwei Zhou, Zhongkui Li, Zhenjie Tang, Zhongshi Wu, Hao Tang Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China Background: Cell therapy is a promising strategy f...

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Autores principales: Wang B, Tan L, Deng D, Lu T, Zhou C, Li Z, Tang Z, Wu Z, Tang H
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
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Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/266536e2015d479c95237f6f79466334
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spelling oai:doaj.org-article:266536e2015d479c95237f6f794663342021-12-02T03:54:12ZNovel stable cytokine delivery system in physiological pH solution: chitosan oligosaccharide/heparin nanoparticles1178-2013https://doaj.org/article/266536e2015d479c95237f6f794663342015-05-01T00:00:00Zhttp://www.dovepress.com/novel-stable-cytokine-delivery-systemnbspin-physiological-ph-solution--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Bin Wang, Ling Tan, Dengpu Deng, Ting Lu, Changwei Zhou, Zhongkui Li, Zhenjie Tang, Zhongshi Wu, Hao Tang Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China Background: Cell therapy is a promising strategy for tissue regeneration. Key to this strategy is mobilization and recruitment of exogenous or autologous stem/progenitor cells by cytokines. However, there is no effective cytokine delivery system available for clinic application, in particular for myocardial regeneration. The aim of this study was to develop a novel cytokine delivery system that is stable in solution at physiological pH. Methods: Four groups of self-assembled chitosan oligosaccharide/heparin (CSO/H) nanoparticles were prepared with various volume ratios of chitosan oligosaccharide to heparin (5:2, 5:4, 4:15, 1:5) and characterized by laser diffraction, particle size analysis, and transmission electron microscopy. The encapsulation efficiency and loading content of two cytokines, ie, stromal cell-derived factor (SDF)-1α and vascular endothelial growth factor (VEGF) were quantified using an enzyme-linked immunosorbent assay. The biological activity of the loaded SDF-1α and VEGF was evaluated using the transwell migration assay and MTT assay. The dispersion profiles for the cytokine-loaded nanoparticles were quantified using fluorescence molecular tomography. Results: CSO/H nanoparticles were prepared successfully in solution with physiological pH. The particle sizes in the four treatment groups were in the range of 96.2–210.5 nm and the zeta potential ranged from -29.4 mV to 24.2 mV. The loading efficiency in the CSO/H nanoparticle groups with the first three ratios was more than 90%. SDF-1α loaded into CSO/H nanoparticles retained its migration activity and VEGF loaded into CSO/H nanoparticles continued to show proliferation activity. The in vivo dispersion test showed that the CSO/H nanoparticles enabled to VEGF to accumulate locally for a longer period of time. Conclusion: CSO/H nanoparticles have a high cytokine loading capacity and allow cytokines to maintain their bioactivity for longer, are stable in an environment with physiological pH, and may be a promising cytokine delivery system for tissue regeneration. Keywords: cytokine delivery system, nanoparticles, chitosan oligosaccharide, physiological pH, stromal cell-derived factor-1α, vascular endothelial growth factor Wang BTan LDeng DLu TZhou CLi ZTang ZWu ZTang HDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 3417-3427 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Wang B
Tan L
Deng D
Lu T
Zhou C
Li Z
Tang Z
Wu Z
Tang H
Novel stable cytokine delivery system in physiological pH solution: chitosan oligosaccharide/heparin nanoparticles
description Bin Wang, Ling Tan, Dengpu Deng, Ting Lu, Changwei Zhou, Zhongkui Li, Zhenjie Tang, Zhongshi Wu, Hao Tang Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China Background: Cell therapy is a promising strategy for tissue regeneration. Key to this strategy is mobilization and recruitment of exogenous or autologous stem/progenitor cells by cytokines. However, there is no effective cytokine delivery system available for clinic application, in particular for myocardial regeneration. The aim of this study was to develop a novel cytokine delivery system that is stable in solution at physiological pH. Methods: Four groups of self-assembled chitosan oligosaccharide/heparin (CSO/H) nanoparticles were prepared with various volume ratios of chitosan oligosaccharide to heparin (5:2, 5:4, 4:15, 1:5) and characterized by laser diffraction, particle size analysis, and transmission electron microscopy. The encapsulation efficiency and loading content of two cytokines, ie, stromal cell-derived factor (SDF)-1α and vascular endothelial growth factor (VEGF) were quantified using an enzyme-linked immunosorbent assay. The biological activity of the loaded SDF-1α and VEGF was evaluated using the transwell migration assay and MTT assay. The dispersion profiles for the cytokine-loaded nanoparticles were quantified using fluorescence molecular tomography. Results: CSO/H nanoparticles were prepared successfully in solution with physiological pH. The particle sizes in the four treatment groups were in the range of 96.2–210.5 nm and the zeta potential ranged from -29.4 mV to 24.2 mV. The loading efficiency in the CSO/H nanoparticle groups with the first three ratios was more than 90%. SDF-1α loaded into CSO/H nanoparticles retained its migration activity and VEGF loaded into CSO/H nanoparticles continued to show proliferation activity. The in vivo dispersion test showed that the CSO/H nanoparticles enabled to VEGF to accumulate locally for a longer period of time. Conclusion: CSO/H nanoparticles have a high cytokine loading capacity and allow cytokines to maintain their bioactivity for longer, are stable in an environment with physiological pH, and may be a promising cytokine delivery system for tissue regeneration. Keywords: cytokine delivery system, nanoparticles, chitosan oligosaccharide, physiological pH, stromal cell-derived factor-1α, vascular endothelial growth factor 
format article
author Wang B
Tan L
Deng D
Lu T
Zhou C
Li Z
Tang Z
Wu Z
Tang H
author_facet Wang B
Tan L
Deng D
Lu T
Zhou C
Li Z
Tang Z
Wu Z
Tang H
author_sort Wang B
title Novel stable cytokine delivery system in physiological pH solution: chitosan oligosaccharide/heparin nanoparticles
title_short Novel stable cytokine delivery system in physiological pH solution: chitosan oligosaccharide/heparin nanoparticles
title_full Novel stable cytokine delivery system in physiological pH solution: chitosan oligosaccharide/heparin nanoparticles
title_fullStr Novel stable cytokine delivery system in physiological pH solution: chitosan oligosaccharide/heparin nanoparticles
title_full_unstemmed Novel stable cytokine delivery system in physiological pH solution: chitosan oligosaccharide/heparin nanoparticles
title_sort novel stable cytokine delivery system in physiological ph solution: chitosan oligosaccharide/heparin nanoparticles
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/266536e2015d479c95237f6f79466334
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