Codelivery of zoledronic acid and double-stranded RNA from core-shell nanoparticles

Li Chen,1 Yunfei Ding,2 Yongzhong Wang,3 Xingrong Liu,2 RJ Babu,1 WR Ravis,1 Weili Yan21Department of Pharmaceutical Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA; 2Department of Pharmaceutical Sciences, College of Life Sciences and Engineering, Southwest Jiaotong Univers...

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Autores principales:	Yan W, Ravis WR, Babu RJ, Liu X, Wang Y, Ding Y, Chen L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0c90e63bc9b44ed3816b26aac4b162e8
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spelling	oai:doaj.org-article:0c90e63bc9b44ed3816b26aac4b162e82021-12-02T08:25:29ZCodelivery of zoledronic acid and double-stranded RNA from core-shell nanoparticles1176-91141178-2013https://doaj.org/article/0c90e63bc9b44ed3816b26aac4b162e82013-01-01T00:00:00Zhttp://www.dovepress.com/codelivery-of-zoledronic-acid-and-double-stranded-rna-from-core-shell--a11864https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Li Chen,1 Yunfei Ding,2 Yongzhong Wang,3 Xingrong Liu,2 RJ Babu,1 WR Ravis,1 Weili Yan21Department of Pharmaceutical Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA; 2Department of Pharmaceutical Sciences, College of Life Sciences and Engineering, Southwest Jiaotong University, Chengdu, China; 3School of Life Sciences, Anhui University, Hefei, ChinaBackground: Zoledronic acid, an inhibitor of osteoclast-mediated bone resorption, has been shown to have both direct and indirect antitumor activity. However, its use in extraskeletal malignancy is limited due to rapid uptake and accumulation within bone. Polyinosinic acid-polycytidylic acid [poly (I:C)] is a synthetic double-stranded RNA with direct antitumor cytotoxicity if it can be delivered to tumor cells intracellularly.Methods: Cationic lipid-coated calcium phosphate nanoparticles (LCP) were developed to enable intracellular codelivery of zoledronic acid and poly (I:C). LCP codelivering zoledronic acid and poly (I:C) were prepared using an ethanol injection method. Briefly, the ethanol solution of lipids was rapidly injected into newly formed calcium phosphate crystals containing poly (I:C) and zoledronic acid, and the mixture was then sonicated briefly to form LCP. The LCP were fully characterized for mean diameter size and zeta potential, efficiency in loading zoledronic acid, cytotoxic effect in a B16BL6 melanoma cell line in vitro, and antitumor effect in B16BL6 melanoma-bearing mice.Results: LCP with a mean diameter around 200 nm and a narrow size distribution (polydispersity index 0.17) and high zoledronic acid encapsulation efficiency (94%) were achieved. LCP loaded with zoledronic acid and poly (I:C) had significantly greater antitumor activity than the free drugs in the B16BL6 melanoma cell line (P &lt; 0.05). Furthermore, codelivery of zoledronic acid and poly (I:C) by LCP had higher cytotoxicity than delivering poly (I:C) alone by LCP (P &lt; 0.05), indicating a synergism between zoledronic acid and poly (I:C). Finally, the antitumor study in melanoma-bearing mice also demonstrated synergism between zoledronic acid and poly (I:C) codelivered by LCP.Conclusion: Cationic lipid-coated calcium phosphate nanoparticles constructed for codelivery of zoledronic acid and double-stranded RNA poly (I:C) had better antitumor activity both in vitro and in vivo. Future preclinical development of LCP encapsulating zoledronic acid and poly (I:C) for the treatment of human cancer is under way.Keywords: calcium phosphate, lipid-coated nanoparticles, zoledronic acid, double-stranded RNA, poly (I:C), codeliveryYan WRavis WRBabu RJLiu XWang YDing YChen LDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 137-145 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Yan W Ravis WR Babu RJ Liu X Wang Y Ding Y Chen L Codelivery of zoledronic acid and double-stranded RNA from core-shell nanoparticles
description	Li Chen,1 Yunfei Ding,2 Yongzhong Wang,3 Xingrong Liu,2 RJ Babu,1 WR Ravis,1 Weili Yan21Department of Pharmaceutical Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA; 2Department of Pharmaceutical Sciences, College of Life Sciences and Engineering, Southwest Jiaotong University, Chengdu, China; 3School of Life Sciences, Anhui University, Hefei, ChinaBackground: Zoledronic acid, an inhibitor of osteoclast-mediated bone resorption, has been shown to have both direct and indirect antitumor activity. However, its use in extraskeletal malignancy is limited due to rapid uptake and accumulation within bone. Polyinosinic acid-polycytidylic acid [poly (I:C)] is a synthetic double-stranded RNA with direct antitumor cytotoxicity if it can be delivered to tumor cells intracellularly.Methods: Cationic lipid-coated calcium phosphate nanoparticles (LCP) were developed to enable intracellular codelivery of zoledronic acid and poly (I:C). LCP codelivering zoledronic acid and poly (I:C) were prepared using an ethanol injection method. Briefly, the ethanol solution of lipids was rapidly injected into newly formed calcium phosphate crystals containing poly (I:C) and zoledronic acid, and the mixture was then sonicated briefly to form LCP. The LCP were fully characterized for mean diameter size and zeta potential, efficiency in loading zoledronic acid, cytotoxic effect in a B16BL6 melanoma cell line in vitro, and antitumor effect in B16BL6 melanoma-bearing mice.Results: LCP with a mean diameter around 200 nm and a narrow size distribution (polydispersity index 0.17) and high zoledronic acid encapsulation efficiency (94%) were achieved. LCP loaded with zoledronic acid and poly (I:C) had significantly greater antitumor activity than the free drugs in the B16BL6 melanoma cell line (P &lt; 0.05). Furthermore, codelivery of zoledronic acid and poly (I:C) by LCP had higher cytotoxicity than delivering poly (I:C) alone by LCP (P &lt; 0.05), indicating a synergism between zoledronic acid and poly (I:C). Finally, the antitumor study in melanoma-bearing mice also demonstrated synergism between zoledronic acid and poly (I:C) codelivered by LCP.Conclusion: Cationic lipid-coated calcium phosphate nanoparticles constructed for codelivery of zoledronic acid and double-stranded RNA poly (I:C) had better antitumor activity both in vitro and in vivo. Future preclinical development of LCP encapsulating zoledronic acid and poly (I:C) for the treatment of human cancer is under way.Keywords: calcium phosphate, lipid-coated nanoparticles, zoledronic acid, double-stranded RNA, poly (I:C), codelivery
format	article
author	Yan W Ravis WR Babu RJ Liu X Wang Y Ding Y Chen L
author_facet	Yan W Ravis WR Babu RJ Liu X Wang Y Ding Y Chen L
author_sort	Yan W
title	Codelivery of zoledronic acid and double-stranded RNA from core-shell nanoparticles
title_short	Codelivery of zoledronic acid and double-stranded RNA from core-shell nanoparticles
title_full	Codelivery of zoledronic acid and double-stranded RNA from core-shell nanoparticles
title_fullStr	Codelivery of zoledronic acid and double-stranded RNA from core-shell nanoparticles
title_full_unstemmed	Codelivery of zoledronic acid and double-stranded RNA from core-shell nanoparticles
title_sort	codelivery of zoledronic acid and double-stranded rna from core-shell nanoparticles
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/0c90e63bc9b44ed3816b26aac4b162e8
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Codelivery of zoledronic acid and double-stranded RNA from core-shell nanoparticles

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