Improved pharmacokinetics and reduced toxicity of brucine after encapsulation into stealth liposomes: role of phosphatidylcholine

Jun Chen,1,* Guo-jun Yan,1,* Rong-rong Hu,1 Qian-wen Gu,1 Ming-lei Chen,1 Wei Gu,1 Zhi-peng Chen,1 Bao-chang Cai1,2 1College of Pharmacy, 2Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing, People&...

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Autores principales:	Chen J, Yan GJ, Hu RR, Gu QW, Chen ML, Gu W, Chen ZP, Cai BC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/149517160c464866b441e8cd8086fd03
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spelling	oai:doaj.org-article:149517160c464866b441e8cd8086fd032021-12-02T07:28:32ZImproved pharmacokinetics and reduced toxicity of brucine after encapsulation into stealth liposomes: role of phosphatidylcholine1176-91141178-2013https://doaj.org/article/149517160c464866b441e8cd8086fd032012-07-01T00:00:00Zhttp://www.dovepress.com/improved-pharmacokinetics-and-reduced-toxicity-of-brucine-after-encaps-a10517https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Jun Chen,1,* Guo-jun Yan,1,* Rong-rong Hu,1 Qian-wen Gu,1 Ming-lei Chen,1 Wei Gu,1 Zhi-peng Chen,1 Bao-chang Cai1,2 1College of Pharmacy, 2Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing, People&#39;s Republic of China *These authors contributed equally to this projectObjective: Brucine was encapsulated into stealth liposomes using the ammonium sulfate gradient method to improve therapeutic index.Materials and methods: Four brucine stealth liposomal formulations were prepared, which were made from different phosphatidylcholines (PCs) with different phase transition temperatures (Tm). The PCs used were soy phosphatidylcholine (SPC), dipalmitoyl phosphatidylcholine (DPPC), hydrogenated soy phosphatidylcholine (HSPC), and distearoyl phosphatidylcholine (DSPC). The stabilities, pharmacokinetics, and toxicities of these liposomal formulations were evaluated and compared.Results: Size, zeta potential, and entrapment efficiency of brucine-loaded stealth liposomes (BSL) were not influenced by PC composition. In vitro release studies revealed that drug release rate increased with decreased Tm of PCs, especially with the presence of rat plasma. After intravenous administration, the area under the curve (AUC) values of BSL-SPC, BSL-DPPC, BSL-HSPC, and BSL-DSPC in plasma were 7.71, 9.24, 53.83, and 56.83-fold as large as that of free brucine, respectively. The LD50 values of brucine solution, BSL-SPC, BSL-DPPC, BSL-HSPC, and BSL-DSPC following intravenous injection were 13.17, 37.30, 37.69, 51.18, and 52.86 mg/kg, respectively. It was found in calcein retention experiments that the order of calcein retention in rat plasma was SPC &lt; DPPC &lt;&lt; HSPC &lt; DSPC stealth liposomes.Conclusion: PC composition could exert significant influence on the stabilities, pharmacokinetics, and toxicities of brucine-loaded stealth liposomes. DSPC or HSPC with Tm above 50&deg;C should be used to prepare the stealth liposomal formulation for the intravenous delivery of brucine. However, it was found in the present paper that the pharmacokinetics and toxicity of BSL were not influenced by the PC composition when the Tm of the PC was in the range of &ndash;20&deg;C to 41&deg;C.Keywords: brucine, stealth liposomes, phosphatidylcholine, pharmacokinetics, toxicityChen JYan GJHu RRGu QWChen MLGu WChen ZPCai BCDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 3567-3577 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Chen J Yan GJ Hu RR Gu QW Chen ML Gu W Chen ZP Cai BC Improved pharmacokinetics and reduced toxicity of brucine after encapsulation into stealth liposomes: role of phosphatidylcholine
description	Jun Chen,1,* Guo-jun Yan,1,* Rong-rong Hu,1 Qian-wen Gu,1 Ming-lei Chen,1 Wei Gu,1 Zhi-peng Chen,1 Bao-chang Cai1,2 1College of Pharmacy, 2Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing, People&#39;s Republic of China *These authors contributed equally to this projectObjective: Brucine was encapsulated into stealth liposomes using the ammonium sulfate gradient method to improve therapeutic index.Materials and methods: Four brucine stealth liposomal formulations were prepared, which were made from different phosphatidylcholines (PCs) with different phase transition temperatures (Tm). The PCs used were soy phosphatidylcholine (SPC), dipalmitoyl phosphatidylcholine (DPPC), hydrogenated soy phosphatidylcholine (HSPC), and distearoyl phosphatidylcholine (DSPC). The stabilities, pharmacokinetics, and toxicities of these liposomal formulations were evaluated and compared.Results: Size, zeta potential, and entrapment efficiency of brucine-loaded stealth liposomes (BSL) were not influenced by PC composition. In vitro release studies revealed that drug release rate increased with decreased Tm of PCs, especially with the presence of rat plasma. After intravenous administration, the area under the curve (AUC) values of BSL-SPC, BSL-DPPC, BSL-HSPC, and BSL-DSPC in plasma were 7.71, 9.24, 53.83, and 56.83-fold as large as that of free brucine, respectively. The LD50 values of brucine solution, BSL-SPC, BSL-DPPC, BSL-HSPC, and BSL-DSPC following intravenous injection were 13.17, 37.30, 37.69, 51.18, and 52.86 mg/kg, respectively. It was found in calcein retention experiments that the order of calcein retention in rat plasma was SPC &lt; DPPC &lt;&lt; HSPC &lt; DSPC stealth liposomes.Conclusion: PC composition could exert significant influence on the stabilities, pharmacokinetics, and toxicities of brucine-loaded stealth liposomes. DSPC or HSPC with Tm above 50&deg;C should be used to prepare the stealth liposomal formulation for the intravenous delivery of brucine. However, it was found in the present paper that the pharmacokinetics and toxicity of BSL were not influenced by the PC composition when the Tm of the PC was in the range of &ndash;20&deg;C to 41&deg;C.Keywords: brucine, stealth liposomes, phosphatidylcholine, pharmacokinetics, toxicity
format	article
author	Chen J Yan GJ Hu RR Gu QW Chen ML Gu W Chen ZP Cai BC
author_facet	Chen J Yan GJ Hu RR Gu QW Chen ML Gu W Chen ZP Cai BC
author_sort	Chen J
title	Improved pharmacokinetics and reduced toxicity of brucine after encapsulation into stealth liposomes: role of phosphatidylcholine
title_short	Improved pharmacokinetics and reduced toxicity of brucine after encapsulation into stealth liposomes: role of phosphatidylcholine
title_full	Improved pharmacokinetics and reduced toxicity of brucine after encapsulation into stealth liposomes: role of phosphatidylcholine
title_fullStr	Improved pharmacokinetics and reduced toxicity of brucine after encapsulation into stealth liposomes: role of phosphatidylcholine
title_full_unstemmed	Improved pharmacokinetics and reduced toxicity of brucine after encapsulation into stealth liposomes: role of phosphatidylcholine
title_sort	improved pharmacokinetics and reduced toxicity of brucine after encapsulation into stealth liposomes: role of phosphatidylcholine
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/149517160c464866b441e8cd8086fd03
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Improved pharmacokinetics and reduced toxicity of brucine after encapsulation into stealth liposomes: role of phosphatidylcholine

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