Comparison of toxicokinetic and tissue distribution of triptolide-loaded solid lipid nanoparticles vs free triptolide in rats

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	Comparison of toxicokinetic and tissue distribution of triptolide-loaded solid lipid nanoparticles vs free triptolide in rats
	Xue, Mei ; Zhao, Yan ; Li, Xue-jun ; Jiang, Zhen-zhou ; Zhang, Liang ; Liu, Su-huan ; Li, Xiu-min ; Zhang, Lu-Yong ; Yang, Shu-yu ; Yang SY(杨叔禹)
刊名	http://dx.doi.org/10.1016/j.ejps.2012.05.012
	2012-11-20
关键词	CELLS ARTHRITIS PATHWAY
英文摘要	Specific Fund for Public Interest Research of Traditional Chinese Medicine, Ministry of Finance [200707008]; Megaprojects of Science Research for the 11th Five-Year Plan: Standardized Platform Construction and Scientific Application in New Technologies for New Drug Screening [2009ZX09302-002]; The traditional Chinese medicine Tripterygium wilfordii Hook F (TWHF) is used clinically to treat some autoimmune and inflammatory disorders including rheumatoid arthritis, systemic lupus erythematosus, and skin diseases. However TWHF has a high potential for toxicity, so its clinical use is limited. Solid lipid nanoparticle (SLN) delivery systems are reported to have remarkable advantages over conventional formulations of bioactive plant extracts, such as enhancing solubility and bioavailability, offering protection from toxicity, and enhancing pharmacological activity. We reported previously that a tripterygium glycoside (TG) solid lipid nanoparticle (TG-SLN) delivery system had a protective effect against TG-induced male reproductive toxicity. To better understand this issue, we used triptolide (TP) as a model drug in a comparative study of the toxicokinetic and tissue distribution of TP-SLN and free TP in rats, allowing us to observing the in vivo behavior of this nanoformulation and to assess mechanisms of SLN-related toxicity. A fast and sensitive HPLC-APCI-MS/MS method was developed for the determination of triptolide in rat plasma. Fourteen rats were divided randomly into two groups of 7 rats each for toxicokinetic analysis, with one group receiving free TP (450 mu g/kg) and the other receiving the TP-SLN formulation (450 mu g/kg). Blood was obtained before dosing and 0.083, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3 and 4 h after drug administration. Thirty-six rats were divided randomly into six equal groups for a tissue-distribution study. Half of the rats received intragastric administration of TP (450 mu g/kg) and the other half received TP-SLN (450 mu g/kg). At 15, 45, and 90 min after dosing, samples of blood, liver, kidney, spleen, lung, and testicular tissue were taken. TP concentration in the samples was determined by LC-APCI-MS-MS. The toxicokinetic results for the nanoformulation showed a significant increase the area under the curve (AUC) (P < 0.05). significantly longer T-max and mean retention times (MRTs) (0-t)(P < 0.05), significantly decreased C-max (P < 0.05). The nanoformulation promoted absorption with a slow release character, indicating that toxicokinetic changes may be the most important mechanism for the enhanced efficacy of nanoformulations. Tissue-distribution results suggest a tendency for TP concentrations in the lung and spleen to increase, while TP concentrations in plasma, liver, kidney, and testes tended to decrease in the TP-SLN group. At multiple time points, testicular tissue TP concentrations were lower in the TP-SLN group than in free TP group. This provides an important clue for the decreased reproductive toxicity observed with TP-SLN. Crown Copyright (C) 2012 Published by Elsevier B.V. All rights reserved.
语种	英语
出版者	EUR J PHARM SCI
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/93088]
专题	医学院－已发表论文
推荐引用方式 GB/T 7714	Xue, Mei,Zhao, Yan,Li, Xue-jun,et al. Comparison of toxicokinetic and tissue distribution of triptolide-loaded solid lipid nanoparticles vs free triptolide in rats[J]. http://dx.doi.org/10.1016/j.ejps.2012.05.012,2012.
APA	Xue, Mei.,Zhao, Yan.,Li, Xue-jun.,Jiang, Zhen-zhou.,Zhang, Liang.,...&杨叔禹.(2012).Comparison of toxicokinetic and tissue distribution of triptolide-loaded solid lipid nanoparticles vs free triptolide in rats.http://dx.doi.org/10.1016/j.ejps.2012.05.012.
MLA	Xue, Mei,et al."Comparison of toxicokinetic and tissue distribution of triptolide-loaded solid lipid nanoparticles vs free triptolide in rats".http://dx.doi.org/10.1016/j.ejps.2012.05.012 (2012).