Optimization and physicochemical characterization of a cationic lipid-phosphatidylcholine mixed emulsion formulated as a highly efficient vehicle that facilitates adenoviral gene transfer

Soo-Yeon Kim,1,2 Sang-Jin Lee,2 Jin-Ki Kim,3 Han-Gon Choi,3 Soo-Jeong Lim1 1Department of Bioscience and Bioengineering, Sejong University, Seoul, Kwangjin-gu, Seoul, 2Immunotherapeutics Branch, Research Institute, National Cancer Center, Ilsandong-gu, Goyang-si, Gyeonggi-do, 3College of Pharmacy &...

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Autores principales:	Kim SY, Lee SJ, Kim JK, Choi HG, Lim SJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	cationic lipid oil emulsion adenovirus gene delivery Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0516cedf3f50489396814e3e902411bd
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spelling	oai:doaj.org-article:0516cedf3f50489396814e3e902411bd2021-12-02T01:34:06ZOptimization and physicochemical characterization of a cationic lipid-phosphatidylcholine mixed emulsion formulated as a highly efficient vehicle that facilitates adenoviral gene transfer1178-2013https://doaj.org/article/0516cedf3f50489396814e3e902411bd2017-10-01T00:00:00Zhttps://www.dovepress.com/optimization-and-physicochemical-characterization-of-a-cationic-lipid--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Soo-Yeon Kim,1,2 Sang-Jin Lee,2 Jin-Ki Kim,3 Han-Gon Choi,3 Soo-Jeong Lim1 1Department of Bioscience and Bioengineering, Sejong University, Seoul, Kwangjin-gu, Seoul, 2Immunotherapeutics Branch, Research Institute, National Cancer Center, Ilsandong-gu, Goyang-si, Gyeonggi-do, 3College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, Sangnok-gu, Ansan, Republic of Korea Abstract: Cationic lipid-based nanoparticles enhance viral gene transfer by forming electrostatic complexes with adenoviral vectors. We recently demonstrated the superior complexation capabilities of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) emulsion compared with a liposomal counterpart but the cytotoxicity of DOTAP emulsions remained a challenge. The present study is aimed at formulating an emulsion capable of acting as a highly effective viral gene transfer vehicle with reduced cytotoxicity and to physicochemically characterize the structures of virus-emulsion complexes in comparison with virus–liposome complexes when the only difference between emulsions and liposomes was the presence or absence of inner oil core. The emulsion formulation was performed by 1) reducing the content of DOTAP while increasing the content of zwitterionic lipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 2) optimizing the oil content. The complexation capability of formulated DOTAP:DMPC mixed emulsions was similar to those of emulsions containing DOTAP alone while displaying significantly lower cytotoxicity. The complexation capabilities of the DOTAP:DMPC mixed emulsion were serum-compatible and were monitored in a variety of cell types, whereas its liposomal counterpart was totally ineffective. Characterization by scanning electron microscopy, transmission electron microscopy, atomic force microscopy, and dynamic light scattering studies indicated that the optimized emulsions spontaneously surrounded the virus particles to generate emulsions that encapsulated the viral particles, whereas viral particles merely attached to the surfaces of the counterpart liposomes to form multiviral aggregates. Overall, these studies demonstrated that optimized DOTAP:DMPC mixed emulsions are potentially useful for adenoviral gene delivery due to less cytotoxicity and the unique ability to encapsulate the viral particle, highlighting the importance of nanoparticle formulation. Keywords: cationic lipid, oil, emulsion, adenovirus, gene delivery Kim SYLee SJKim JKChoi HGLim SJDove Medical Pressarticlecationic lipidoilemulsionadenovirusgene deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 7323-7335 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	cationic lipid oil emulsion adenovirus gene delivery Medicine (General) R5-920
spellingShingle	cationic lipid oil emulsion adenovirus gene delivery Medicine (General) R5-920 Kim SY Lee SJ Kim JK Choi HG Lim SJ Optimization and physicochemical characterization of a cationic lipid-phosphatidylcholine mixed emulsion formulated as a highly efficient vehicle that facilitates adenoviral gene transfer
description	Soo-Yeon Kim,1,2 Sang-Jin Lee,2 Jin-Ki Kim,3 Han-Gon Choi,3 Soo-Jeong Lim1 1Department of Bioscience and Bioengineering, Sejong University, Seoul, Kwangjin-gu, Seoul, 2Immunotherapeutics Branch, Research Institute, National Cancer Center, Ilsandong-gu, Goyang-si, Gyeonggi-do, 3College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, Sangnok-gu, Ansan, Republic of Korea Abstract: Cationic lipid-based nanoparticles enhance viral gene transfer by forming electrostatic complexes with adenoviral vectors. We recently demonstrated the superior complexation capabilities of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) emulsion compared with a liposomal counterpart but the cytotoxicity of DOTAP emulsions remained a challenge. The present study is aimed at formulating an emulsion capable of acting as a highly effective viral gene transfer vehicle with reduced cytotoxicity and to physicochemically characterize the structures of virus-emulsion complexes in comparison with virus–liposome complexes when the only difference between emulsions and liposomes was the presence or absence of inner oil core. The emulsion formulation was performed by 1) reducing the content of DOTAP while increasing the content of zwitterionic lipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 2) optimizing the oil content. The complexation capability of formulated DOTAP:DMPC mixed emulsions was similar to those of emulsions containing DOTAP alone while displaying significantly lower cytotoxicity. The complexation capabilities of the DOTAP:DMPC mixed emulsion were serum-compatible and were monitored in a variety of cell types, whereas its liposomal counterpart was totally ineffective. Characterization by scanning electron microscopy, transmission electron microscopy, atomic force microscopy, and dynamic light scattering studies indicated that the optimized emulsions spontaneously surrounded the virus particles to generate emulsions that encapsulated the viral particles, whereas viral particles merely attached to the surfaces of the counterpart liposomes to form multiviral aggregates. Overall, these studies demonstrated that optimized DOTAP:DMPC mixed emulsions are potentially useful for adenoviral gene delivery due to less cytotoxicity and the unique ability to encapsulate the viral particle, highlighting the importance of nanoparticle formulation. Keywords: cationic lipid, oil, emulsion, adenovirus, gene delivery
format	article
author	Kim SY Lee SJ Kim JK Choi HG Lim SJ
author_facet	Kim SY Lee SJ Kim JK Choi HG Lim SJ
author_sort	Kim SY
title	Optimization and physicochemical characterization of a cationic lipid-phosphatidylcholine mixed emulsion formulated as a highly efficient vehicle that facilitates adenoviral gene transfer
title_short	Optimization and physicochemical characterization of a cationic lipid-phosphatidylcholine mixed emulsion formulated as a highly efficient vehicle that facilitates adenoviral gene transfer
title_full	Optimization and physicochemical characterization of a cationic lipid-phosphatidylcholine mixed emulsion formulated as a highly efficient vehicle that facilitates adenoviral gene transfer
title_fullStr	Optimization and physicochemical characterization of a cationic lipid-phosphatidylcholine mixed emulsion formulated as a highly efficient vehicle that facilitates adenoviral gene transfer
title_full_unstemmed	Optimization and physicochemical characterization of a cationic lipid-phosphatidylcholine mixed emulsion formulated as a highly efficient vehicle that facilitates adenoviral gene transfer
title_sort	optimization and physicochemical characterization of a cationic lipid-phosphatidylcholine mixed emulsion formulated as a highly efficient vehicle that facilitates adenoviral gene transfer
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/0516cedf3f50489396814e3e902411bd
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Optimization and physicochemical characterization of a cationic lipid-phosphatidylcholine mixed emulsion formulated as a highly efficient vehicle that facilitates adenoviral gene transfer

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