Efficient gene transfection to the brain with ultrasound irradiation in mice using stabilized bubble lipopolyplexes prepared by the surface charge regulation method

Koki Ogawa,1,* Yuki Fuchigami,1,* Masayori Hagimori,1 Shintaro Fumoto,2 Yusuke Miura,1 Shigeru Kawakami1 1Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan; 2Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nag...

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Autores principales:	Ogawa K, Fuchigami Y, Hagimori M, Fumoto S, Miura Y, Kawakami S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Gene delivery brain bubble lipopolyplex echo gas spatial distribution Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/94674f281cfd45f591c51bed503e5192
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spelling	oai:doaj.org-article:94674f281cfd45f591c51bed503e51922021-12-02T06:01:12ZEfficient gene transfection to the brain with ultrasound irradiation in mice using stabilized bubble lipopolyplexes prepared by the surface charge regulation method1178-2013https://doaj.org/article/94674f281cfd45f591c51bed503e51922018-04-01T00:00:00Zhttps://www.dovepress.com/efficient-gene-transfection-to-the-brain-with-ultrasound-irradiation-i-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Koki Ogawa,1,* Yuki Fuchigami,1,* Masayori Hagimori,1 Shintaro Fumoto,2 Yusuke Miura,1 Shigeru Kawakami1 1Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan; 2Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan *These authors contributed equally to this work Introduction: We previously developed anionic ternary bubble lipopolyplexes, an ultrasound-responsive carrier, expecting safe and efficient gene transfection. However, bubble lipopolyplexes have a low capacity for echo gas (C3F8) encapsulation (EGE) in nonionic solution such as 5% glucose. On the other hand, we were able to prepare bubble lipopolyplexes by inserting phosphate-buffered saline before C3F8 encapsulation. Surface charge regulation (SCR) by electrolytes stabilizes liposome/plasmid DNA (pDNA) complexes by accelerated membrane fusion. Considering these facts, we hypothesized that SCR by electrolytes such as NaCl would promote C3F8 encapsulation in bubble lipopolyplexes mediated by accelerated membrane fusion. We defined this hypothesis as SCR-based EGE (SCR-EGE). Bubble lipopolyplexes prepared by the SCR-EGE method (SCR-EGE bubble lipopolyplexes) are expected to facilitate the gene transfection because of the high amount of C3F8. Therefore, we applied these methods for gene delivery to the brain and evaluated the characteristics of transgene expression in the brain.Methods: First, we measured the encapsulation efficiency of C3F8 in SCR-EGE bubble lipopolyplexes. Next, we applied these bubble lipopolyplexes to the mouse brain; then, we evaluated the transfection efficiency. Furthermore, three-dimensional transgene distribution was observed using multicolor deep imaging.Results: SCR-EGE bubble lipopolyplexes had a higher C3F8 content than conventional bubble lipopolyplexes. In terms of safety, SCR-EGE bubble lipopolyplexes possessed an anionic potential and showed no aggregation with erythrocytes. After applying SCR-EGE bubble lipopolyplexes to the brain, high transgene expression was observed by combining with ultrasound irradiation. As a result, transgene expression mediated by SCR-EGE bubble lipopolyplexes was observed mainly on blood vessels and partially outside of blood vessels.Conclusion: The SCR-EGE method may promote C3F8 encapsulation in bubble lipopolyplexes, and SCR-EGE bubble lipopolyplexes may be potent carriers for efficient and safe gene transfection in the brain, especially to the blood vessels. Keywords: gene delivery, brain, bubble lipopolyplex, echo gas, spatial distributionOgawa KFuchigami YHagimori MFumoto SMiura YKawakami SDove Medical PressarticleGene deliverybrainbubble lipopolyplexecho gasspatial distributionMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 2309-2320 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Gene delivery brain bubble lipopolyplex echo gas spatial distribution Medicine (General) R5-920
spellingShingle	Gene delivery brain bubble lipopolyplex echo gas spatial distribution Medicine (General) R5-920 Ogawa K Fuchigami Y Hagimori M Fumoto S Miura Y Kawakami S Efficient gene transfection to the brain with ultrasound irradiation in mice using stabilized bubble lipopolyplexes prepared by the surface charge regulation method
description	Koki Ogawa,1,* Yuki Fuchigami,1,* Masayori Hagimori,1 Shintaro Fumoto,2 Yusuke Miura,1 Shigeru Kawakami1 1Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan; 2Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan *These authors contributed equally to this work Introduction: We previously developed anionic ternary bubble lipopolyplexes, an ultrasound-responsive carrier, expecting safe and efficient gene transfection. However, bubble lipopolyplexes have a low capacity for echo gas (C3F8) encapsulation (EGE) in nonionic solution such as 5% glucose. On the other hand, we were able to prepare bubble lipopolyplexes by inserting phosphate-buffered saline before C3F8 encapsulation. Surface charge regulation (SCR) by electrolytes stabilizes liposome/plasmid DNA (pDNA) complexes by accelerated membrane fusion. Considering these facts, we hypothesized that SCR by electrolytes such as NaCl would promote C3F8 encapsulation in bubble lipopolyplexes mediated by accelerated membrane fusion. We defined this hypothesis as SCR-based EGE (SCR-EGE). Bubble lipopolyplexes prepared by the SCR-EGE method (SCR-EGE bubble lipopolyplexes) are expected to facilitate the gene transfection because of the high amount of C3F8. Therefore, we applied these methods for gene delivery to the brain and evaluated the characteristics of transgene expression in the brain.Methods: First, we measured the encapsulation efficiency of C3F8 in SCR-EGE bubble lipopolyplexes. Next, we applied these bubble lipopolyplexes to the mouse brain; then, we evaluated the transfection efficiency. Furthermore, three-dimensional transgene distribution was observed using multicolor deep imaging.Results: SCR-EGE bubble lipopolyplexes had a higher C3F8 content than conventional bubble lipopolyplexes. In terms of safety, SCR-EGE bubble lipopolyplexes possessed an anionic potential and showed no aggregation with erythrocytes. After applying SCR-EGE bubble lipopolyplexes to the brain, high transgene expression was observed by combining with ultrasound irradiation. As a result, transgene expression mediated by SCR-EGE bubble lipopolyplexes was observed mainly on blood vessels and partially outside of blood vessels.Conclusion: The SCR-EGE method may promote C3F8 encapsulation in bubble lipopolyplexes, and SCR-EGE bubble lipopolyplexes may be potent carriers for efficient and safe gene transfection in the brain, especially to the blood vessels. Keywords: gene delivery, brain, bubble lipopolyplex, echo gas, spatial distribution
format	article
author	Ogawa K Fuchigami Y Hagimori M Fumoto S Miura Y Kawakami S
author_facet	Ogawa K Fuchigami Y Hagimori M Fumoto S Miura Y Kawakami S
author_sort	Ogawa K
title	Efficient gene transfection to the brain with ultrasound irradiation in mice using stabilized bubble lipopolyplexes prepared by the surface charge regulation method
title_short	Efficient gene transfection to the brain with ultrasound irradiation in mice using stabilized bubble lipopolyplexes prepared by the surface charge regulation method
title_full	Efficient gene transfection to the brain with ultrasound irradiation in mice using stabilized bubble lipopolyplexes prepared by the surface charge regulation method
title_fullStr	Efficient gene transfection to the brain with ultrasound irradiation in mice using stabilized bubble lipopolyplexes prepared by the surface charge regulation method
title_full_unstemmed	Efficient gene transfection to the brain with ultrasound irradiation in mice using stabilized bubble lipopolyplexes prepared by the surface charge regulation method
title_sort	efficient gene transfection to the brain with ultrasound irradiation in mice using stabilized bubble lipopolyplexes prepared by the surface charge regulation method
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/94674f281cfd45f591c51bed503e5192
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_version_	1718400121798918144

Efficient gene transfection to the brain with ultrasound irradiation in mice using stabilized bubble lipopolyplexes prepared by the surface charge regulation method

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