Nanostructured lipid carriers as a novel oral delivery system for triptolide: induced changes in pharmacokinetics profile associated with reduced toxicity in male rats

Cong Zhang,1 Fan Peng,1 Wei Liu,1 Jiangling Wan,1 Chunxi Wan,1 Huibi Xu,1,2 Christopher Waikei Lam,2 Xiangliang Yang1,2 1National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 2State Key Laboratory of Qual...

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Autores principales:	Zhang C, Peng F, Liu W, Wan J, Wan C, Xu H, Lam CW, Yang X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a571277769a349acbf03261308c7e082
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spelling	oai:doaj.org-article:a571277769a349acbf03261308c7e0822021-12-02T02:06:52ZNanostructured lipid carriers as a novel oral delivery system for triptolide: induced changes in pharmacokinetics profile associated with reduced toxicity in male rats1178-2013https://doaj.org/article/a571277769a349acbf03261308c7e0822014-02-01T00:00:00Zhttp://www.dovepress.com/nanostructured-lipid-carriers-as-a-novel-oral-delivery-system-for-trip-a15898https://doaj.org/toc/1178-2013 Cong Zhang,1 Fan Peng,1 Wei Liu,1 Jiangling Wan,1 Chunxi Wan,1 Huibi Xu,1,2 Christopher Waikei Lam,2 Xiangliang Yang1,2 1National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 2State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, People's Republic of China Abstract: After oral administration in rodents, triptolide (TP), a diterpenoid triepoxide compound, active as anti-inflammatory, immunosuppressive, anti-fertility, anti-cystogenesis, and anticancer agent, is rapidly absorbed into the blood circulation (from 5.0 to 19.5 minutes after dosing, depending on the rodent species) followed by a short elimination half-life (from about 20 minutes to less than 1 hour). Such significant and rapid fluctuations of TP in plasma likely contribute to its toxicity, which is characterized by injury to hepatic, renal, digestive, reproductive, and hematological systems. With the aim of prolonging drug release and improving its safety, TP-loaded nanostructured lipid carriers (TP-NLCs), composed of Compritol® 888 ATO (solid lipid) and Capryol™ 90 (liquid lipid), were developed using a microemulsion technique. The formulated TP-NLCs were also characterized and in vitro release was evaluated using the dialysis bag diffusion technique. In addition, the pharmacokinetics and toxicology profiles of TP-NLCs were compared to free TP and TP-loaded solid lipid nanoparticles (TP-SLNs; containing Compritol 888 ATO only). Results demonstrate that TP-NLCs had mean particle size of 231.8 nm, increased drug encapsulation with a 71.6% efficiency, and stable drug incorporation for over 1-month. TP-NLCs manifested a better in vitro sustained-release pattern compared to TP-SLNs. Furthermore, TP-NLCs prolonged mean residence time (MRT)0–t (P<0.001, P<0.001), delayed Tmax (P<0.01, P<0.05) and decreased Cmax (P<0.01, P<0.05) compared to free TP and TP-SLNs, respectively, which was associated with reduced subacute toxicity in male rats. In conclusion, our data suggest that TP-NLCs are superior to TP-SLNs and could be a promising oral delivery system for a safer use of TP. Keywords: triptolide, microemulsion technique, in vivo pharmacokinetics, sustained-release, rat subacute toxicityZhang CPeng FLiu WWan JWan CXu HLam CWYang XDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 1049-1063 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Zhang C Peng F Liu W Wan J Wan C Xu H Lam CW Yang X Nanostructured lipid carriers as a novel oral delivery system for triptolide: induced changes in pharmacokinetics profile associated with reduced toxicity in male rats
description	Cong Zhang,1 Fan Peng,1 Wei Liu,1 Jiangling Wan,1 Chunxi Wan,1 Huibi Xu,1,2 Christopher Waikei Lam,2 Xiangliang Yang1,2 1National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 2State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, People's Republic of China Abstract: After oral administration in rodents, triptolide (TP), a diterpenoid triepoxide compound, active as anti-inflammatory, immunosuppressive, anti-fertility, anti-cystogenesis, and anticancer agent, is rapidly absorbed into the blood circulation (from 5.0 to 19.5 minutes after dosing, depending on the rodent species) followed by a short elimination half-life (from about 20 minutes to less than 1 hour). Such significant and rapid fluctuations of TP in plasma likely contribute to its toxicity, which is characterized by injury to hepatic, renal, digestive, reproductive, and hematological systems. With the aim of prolonging drug release and improving its safety, TP-loaded nanostructured lipid carriers (TP-NLCs), composed of Compritol® 888 ATO (solid lipid) and Capryol™ 90 (liquid lipid), were developed using a microemulsion technique. The formulated TP-NLCs were also characterized and in vitro release was evaluated using the dialysis bag diffusion technique. In addition, the pharmacokinetics and toxicology profiles of TP-NLCs were compared to free TP and TP-loaded solid lipid nanoparticles (TP-SLNs; containing Compritol 888 ATO only). Results demonstrate that TP-NLCs had mean particle size of 231.8 nm, increased drug encapsulation with a 71.6% efficiency, and stable drug incorporation for over 1-month. TP-NLCs manifested a better in vitro sustained-release pattern compared to TP-SLNs. Furthermore, TP-NLCs prolonged mean residence time (MRT)0–t (P<0.001, P<0.001), delayed Tmax (P<0.01, P<0.05) and decreased Cmax (P<0.01, P<0.05) compared to free TP and TP-SLNs, respectively, which was associated with reduced subacute toxicity in male rats. In conclusion, our data suggest that TP-NLCs are superior to TP-SLNs and could be a promising oral delivery system for a safer use of TP. Keywords: triptolide, microemulsion technique, in vivo pharmacokinetics, sustained-release, rat subacute toxicity
format	article
author	Zhang C Peng F Liu W Wan J Wan C Xu H Lam CW Yang X
author_facet	Zhang C Peng F Liu W Wan J Wan C Xu H Lam CW Yang X
author_sort	Zhang C
title	Nanostructured lipid carriers as a novel oral delivery system for triptolide: induced changes in pharmacokinetics profile associated with reduced toxicity in male rats
title_short	Nanostructured lipid carriers as a novel oral delivery system for triptolide: induced changes in pharmacokinetics profile associated with reduced toxicity in male rats
title_full	Nanostructured lipid carriers as a novel oral delivery system for triptolide: induced changes in pharmacokinetics profile associated with reduced toxicity in male rats
title_fullStr	Nanostructured lipid carriers as a novel oral delivery system for triptolide: induced changes in pharmacokinetics profile associated with reduced toxicity in male rats
title_full_unstemmed	Nanostructured lipid carriers as a novel oral delivery system for triptolide: induced changes in pharmacokinetics profile associated with reduced toxicity in male rats
title_sort	nanostructured lipid carriers as a novel oral delivery system for triptolide: induced changes in pharmacokinetics profile associated with reduced toxicity in male rats
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/a571277769a349acbf03261308c7e082
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Nanostructured lipid carriers as a novel oral delivery system for triptolide: induced changes in pharmacokinetics profile associated with reduced toxicity in male rats

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