In vitro and in vivo evaluation of SN-38 nanocrystals with different particle sizes

Min Chen,1,2 Wanqing Li,3 Xun Zhang,1 Ye Dong,1 Yabing Hua,1 Hui Zhang,1 Jing Gao,1 Liang Zhao,2 Ying Li,1 Aiping Zheng1 1State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 2School of Pharmacy, Jinzhou Medical University, Jinzhou, 3Scho...

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Autores principales:	Chen M, Li W, Zhang X, Dong Y, Hua Y, Zhang H, Gao J, Zhao L, Li Y, Zheng A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	SN-38 nanocrystals antitumor efficacy cellular uptake pharmacokinetics tissue distribution Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/10a100892bd1450fab0ddd29f7cccabc
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spelling	oai:doaj.org-article:10a100892bd1450fab0ddd29f7cccabc2021-12-02T10:40:02ZIn vitro and in vivo evaluation of SN-38 nanocrystals with different particle sizes1178-2013https://doaj.org/article/10a100892bd1450fab0ddd29f7cccabc2017-08-01T00:00:00Zhttps://www.dovepress.com/in-vitro-and-in-vivo-evaluation-of-sn-38-nanocrystals-with-different-p-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Min Chen,1,2 Wanqing Li,3 Xun Zhang,1 Ye Dong,1 Yabing Hua,1 Hui Zhang,1 Jing Gao,1 Liang Zhao,2 Ying Li,1 Aiping Zheng1 1State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 2School of Pharmacy, Jinzhou Medical University, Jinzhou, 3School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China Abstract: 7-Ethyl-10-hydroxycamptothecin (SN-38) is a potent broad-spectrum antitumor drug derived from irinotecan hydrochloride (CPT-11). Due to its poor solubility and instability of the active lactone ring, its clinical use is significantly limited. As one of the most promising formulations for poorly water-soluble drugs, nanocrystals have attracted increasing attention. In order to solve these problems and evaluate the antitumor effect of SN-38 in vitro and in vivo, two nanocrystals with markedly different particle sizes were prepared. Dynamic light scattering and transmission electron microscopy were used to investigate the two nanocrystals. The particle sizes of SN-38 nanocrystals A (SN-38/NCs-A) and SN-38 nanocrystals B (SN-38/NCs-B) were 229.5±1.99 and 799.2±14.44 nm, respectively. X-ray powder diffraction analysis showed that the crystalline state of SN-38 did not change in the size reduction process. An accelerated dissolution velocity of SN-38 was achieved by nanocrystals, and release rate of SN-38/NCs-A was significantly faster than that of SN-38/NCs-B. Cellular uptake, cellular cytotoxicity, pharmacokinetics, animal antitumor efficacy, and tissue distribution were subsequently examined. As a result, enhanced intracellular accumulation in HT1080 cells and cytotoxicity on different tumor cells were observed for SN-38/NCs-A compared to that for SN-38/NCs-B and solution. Besides, compared to the SN-38 solution, SN-38/NCs-A had a higher bioavailability after intravenous injection; while the bioavailability of SN-38/NCs-B was even lower than that of the SN-38 solution. SN-38/NCs-A exhibited a significant inhibition of tumor growth compared to SN-38 solution and SN-38/NCs-B in vivo. The antitumor effect of SN-38/NCs-B was stronger than SN-38 solution. The tissue distribution study in tumor-bearing mice showed that nanocrystals could markedly improve the drug accumulation in tumor tissue by the enhanced permeability and retention effect compared to SN-38 solution, and the amount of SN-38 in tumors of SN-38/NCs-A group was much more than that of SN-38/NCs-B group. In conclusion, nanocrystals dramatically enhanced the anticancer efficacy of SN-38 in vitro and in vivo, and the particle size had a significant influence on the dissolution behavior, pharmacokinetic properties, and tumor inhibition of nanocrystals. Keywords: SN-38, nanocrystals, antitumor efficacy, cellular uptake, pharmacokinetics, tissue distributionChen MLi WZhang XDong YHua YZhang HGao JZhao LLi YZheng ADove Medical PressarticleSN-38nanocrystalsantitumor efficacycellular uptakepharmacokineticstissue distributionMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 5487-5500 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	SN-38 nanocrystals antitumor efficacy cellular uptake pharmacokinetics tissue distribution Medicine (General) R5-920
spellingShingle	SN-38 nanocrystals antitumor efficacy cellular uptake pharmacokinetics tissue distribution Medicine (General) R5-920 Chen M Li W Zhang X Dong Y Hua Y Zhang H Gao J Zhao L Li Y Zheng A In vitro and in vivo evaluation of SN-38 nanocrystals with different particle sizes
description	Min Chen,1,2 Wanqing Li,3 Xun Zhang,1 Ye Dong,1 Yabing Hua,1 Hui Zhang,1 Jing Gao,1 Liang Zhao,2 Ying Li,1 Aiping Zheng1 1State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 2School of Pharmacy, Jinzhou Medical University, Jinzhou, 3School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China Abstract: 7-Ethyl-10-hydroxycamptothecin (SN-38) is a potent broad-spectrum antitumor drug derived from irinotecan hydrochloride (CPT-11). Due to its poor solubility and instability of the active lactone ring, its clinical use is significantly limited. As one of the most promising formulations for poorly water-soluble drugs, nanocrystals have attracted increasing attention. In order to solve these problems and evaluate the antitumor effect of SN-38 in vitro and in vivo, two nanocrystals with markedly different particle sizes were prepared. Dynamic light scattering and transmission electron microscopy were used to investigate the two nanocrystals. The particle sizes of SN-38 nanocrystals A (SN-38/NCs-A) and SN-38 nanocrystals B (SN-38/NCs-B) were 229.5±1.99 and 799.2±14.44 nm, respectively. X-ray powder diffraction analysis showed that the crystalline state of SN-38 did not change in the size reduction process. An accelerated dissolution velocity of SN-38 was achieved by nanocrystals, and release rate of SN-38/NCs-A was significantly faster than that of SN-38/NCs-B. Cellular uptake, cellular cytotoxicity, pharmacokinetics, animal antitumor efficacy, and tissue distribution were subsequently examined. As a result, enhanced intracellular accumulation in HT1080 cells and cytotoxicity on different tumor cells were observed for SN-38/NCs-A compared to that for SN-38/NCs-B and solution. Besides, compared to the SN-38 solution, SN-38/NCs-A had a higher bioavailability after intravenous injection; while the bioavailability of SN-38/NCs-B was even lower than that of the SN-38 solution. SN-38/NCs-A exhibited a significant inhibition of tumor growth compared to SN-38 solution and SN-38/NCs-B in vivo. The antitumor effect of SN-38/NCs-B was stronger than SN-38 solution. The tissue distribution study in tumor-bearing mice showed that nanocrystals could markedly improve the drug accumulation in tumor tissue by the enhanced permeability and retention effect compared to SN-38 solution, and the amount of SN-38 in tumors of SN-38/NCs-A group was much more than that of SN-38/NCs-B group. In conclusion, nanocrystals dramatically enhanced the anticancer efficacy of SN-38 in vitro and in vivo, and the particle size had a significant influence on the dissolution behavior, pharmacokinetic properties, and tumor inhibition of nanocrystals. Keywords: SN-38, nanocrystals, antitumor efficacy, cellular uptake, pharmacokinetics, tissue distribution
format	article
author	Chen M Li W Zhang X Dong Y Hua Y Zhang H Gao J Zhao L Li Y Zheng A
author_facet	Chen M Li W Zhang X Dong Y Hua Y Zhang H Gao J Zhao L Li Y Zheng A
author_sort	Chen M
title	In vitro and in vivo evaluation of SN-38 nanocrystals with different particle sizes
title_short	In vitro and in vivo evaluation of SN-38 nanocrystals with different particle sizes
title_full	In vitro and in vivo evaluation of SN-38 nanocrystals with different particle sizes
title_fullStr	In vitro and in vivo evaluation of SN-38 nanocrystals with different particle sizes
title_full_unstemmed	In vitro and in vivo evaluation of SN-38 nanocrystals with different particle sizes
title_sort	in vitro and in vivo evaluation of sn-38 nanocrystals with different particle sizes
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/10a100892bd1450fab0ddd29f7cccabc
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_version_	1718396867168960512

In vitro and in vivo evaluation of SN-38 nanocrystals with different particle sizes

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