Preclinical studies of N3-O-toluyl-fluorouracil-loaded lipid-based nanosuspensions in H22-bearing mice

Juan Zhang, Min Li, Zhihong Liu, Lili Wang, Yongjun Liu, Na Zhang School of Pharmaceutical Science, Shandong University, Ji’nan, People’s Republic of China Purpose: N3-O-toluyl-fluorouracil (TFU) is a potential antitumor prodrug of 5-fluorouracil (5-FU), but its poor solubilit...

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Autores principales:	Zhang J, Li M, Liu Z, Wang L, Liu Y, Zhang N
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/6d31f37c869b404eb74cd4de624a2cae
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spelling	oai:doaj.org-article:6d31f37c869b404eb74cd4de624a2cae2021-12-02T03:11:32ZPreclinical studies of N3-O-toluyl-fluorouracil-loaded lipid-based nanosuspensions in H22-bearing mice1178-2013https://doaj.org/article/6d31f37c869b404eb74cd4de624a2cae2014-05-01T00:00:00Zhttp://www.dovepress.com/preclinical-studies-of-n3-o-toluyl-fluorouracil-loaded-lipid-based-nan-a17052https://doaj.org/toc/1178-2013 Juan Zhang, Min Li, Zhihong Liu, Lili Wang, Yongjun Liu, Na Zhang School of Pharmaceutical Science, Shandong University, Ji’nan, People’s Republic of China Purpose: N3-O-toluyl-fluorouracil (TFU) is a potential antitumor prodrug of 5-fluorouracil (5-FU), but its poor solubility has limited its use in clinic. This study aimed to improve the bioavailability of TFU by preparing TFU-loaded lipid-based nanosuspensions (TFU-LNS) and perform a preclinical evaluation. Methods: TFU-LNS were prepared through high-pressure homogenization and were lyophilized afterwards. For in vitro test, the physicochemical properties and cytotoxicity against HegG2 cells were conducted. For in vivo evaluation, the pharmacokinetics, tissue distribution, and antitumor efficacy were investigated in H22-bearing Kunming mice. Results: TFU showed different degradability in four media; in particular, nearly all of it converted to an equimolar amount of 5-FU in blank plasma of Wistar rats. The lyophilized TFU-LNS had a mean particle size of 180.03±3.11 nm and zeta potential of –8.02±1.43 mV and showed no discernible changes after storage at 4°C for 3 months. In the in vivo antitumor study, the antitumor efficacy of TFU-LNS was consistent with that of 5-FU injection. Furthermore, TFU-LNS released a lower concentration of 5-FU in heart and kidney throughout the tissue distribution studies. Conclusion: TFU-LNS exhibited convincing antitumor activity and easy scale-up opportunity, which suggests that TFU-LNS might be a promising drug delivery system for cancer therapy.Keywords: 5-fluorouracil, high-pressure homogenization, cytotoxicity, cancer therapyZhang JLi MLiu ZWang LLiu YZhang NDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 2741-2751 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Zhang J Li M Liu Z Wang L Liu Y Zhang N Preclinical studies of N3-O-toluyl-fluorouracil-loaded lipid-based nanosuspensions in H22-bearing mice
description	Juan Zhang, Min Li, Zhihong Liu, Lili Wang, Yongjun Liu, Na Zhang School of Pharmaceutical Science, Shandong University, Ji’nan, People’s Republic of China Purpose: N3-O-toluyl-fluorouracil (TFU) is a potential antitumor prodrug of 5-fluorouracil (5-FU), but its poor solubility has limited its use in clinic. This study aimed to improve the bioavailability of TFU by preparing TFU-loaded lipid-based nanosuspensions (TFU-LNS) and perform a preclinical evaluation. Methods: TFU-LNS were prepared through high-pressure homogenization and were lyophilized afterwards. For in vitro test, the physicochemical properties and cytotoxicity against HegG2 cells were conducted. For in vivo evaluation, the pharmacokinetics, tissue distribution, and antitumor efficacy were investigated in H22-bearing Kunming mice. Results: TFU showed different degradability in four media; in particular, nearly all of it converted to an equimolar amount of 5-FU in blank plasma of Wistar rats. The lyophilized TFU-LNS had a mean particle size of 180.03±3.11 nm and zeta potential of –8.02±1.43 mV and showed no discernible changes after storage at 4°C for 3 months. In the in vivo antitumor study, the antitumor efficacy of TFU-LNS was consistent with that of 5-FU injection. Furthermore, TFU-LNS released a lower concentration of 5-FU in heart and kidney throughout the tissue distribution studies. Conclusion: TFU-LNS exhibited convincing antitumor activity and easy scale-up opportunity, which suggests that TFU-LNS might be a promising drug delivery system for cancer therapy.Keywords: 5-fluorouracil, high-pressure homogenization, cytotoxicity, cancer therapy
format	article
author	Zhang J Li M Liu Z Wang L Liu Y Zhang N
author_facet	Zhang J Li M Liu Z Wang L Liu Y Zhang N
author_sort	Zhang J
title	Preclinical studies of N3-O-toluyl-fluorouracil-loaded lipid-based nanosuspensions in H22-bearing mice
title_short	Preclinical studies of N3-O-toluyl-fluorouracil-loaded lipid-based nanosuspensions in H22-bearing mice
title_full	Preclinical studies of N3-O-toluyl-fluorouracil-loaded lipid-based nanosuspensions in H22-bearing mice
title_fullStr	Preclinical studies of N3-O-toluyl-fluorouracil-loaded lipid-based nanosuspensions in H22-bearing mice
title_full_unstemmed	Preclinical studies of N3-O-toluyl-fluorouracil-loaded lipid-based nanosuspensions in H22-bearing mice
title_sort	preclinical studies of n3-o-toluyl-fluorouracil-loaded lipid-based nanosuspensions in h22-bearing mice
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/6d31f37c869b404eb74cd4de624a2cae
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Preclinical studies of N3-O-toluyl-fluorouracil-loaded lipid-based nanosuspensions in H22-bearing mice

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