Solid lipid nanoparticles reduce systemic toxicity of docetaxel: Performance and mechanism in animal

doi:10.3109/17435390.2010.551427

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物制剂研究中心

	Solid lipid nanoparticles reduce systemic toxicity of docetaxel: Performance and mechanism in animal
	Gao, Yu 1; Yang, Rongfu 2,3; Zhang, Zhiwen1 ; Chen, Lingli1 ; Sun, Zuyue 2,3; Li, Yaping1
刊名	NANOTOXICOLOGY
	2011-12
卷号	5 期号:4 页码:636-649
关键词	Nanotoxicity nanoparticles docetaxel nanomedicine toxicity
ISSN号	1743-5390
DOI	10.3109/17435390.2010.551427
文献子类	Article
英文摘要	Nanotechnology presents great potential for increasing efficacy of docetaxel while reducing side-effects and toxicity. However, in vivo toxicity of nano-formulation of docetaxel has not been systemically investigated yet. Herein, the new docetaxel-loaded solid lipid nanoparticles (DSNs) were prepared, and systemic toxicity of DSNs in different animals was comprehensively investigated. The experimental results showed that no allergenicity and vascular irritation were induced by DSNs at the highest drug concentration of clinical infusion. The maximum tolerated dose (MTD) of DSNs was as high as 400 mg/kg in mice while the medial lethal dose (LD50) of Taxotere (R) was 149.31 mg/kg. The long-term toxicity of DSNs compared with Taxotere (R) in beagle dogs by intravenous infusion weekly for four weeks showed that the administration of Taxotere (R) at 1 mg/kg brought about severe signs of toxicity such as skin flushing, vocalization and salivation. However, no abnormal reactions appeared on animals treated with DSNs at dose of 4 mg/kg. At the same dose level, DSNs induced more minor decreases in body weight gains, slighter hemotoxicity (changes in some clinical hematology and biochemistry parameters), cardiac toxicity, hepatotoxicity and myelosuppression than Taxotere (R). These results could provide an important reference for developing the novel delivery system of docetaxel.
资助项目	National Basic Research Program of China[2010CB934000] ; National Basic Research Program of China[2007CB935800] ; National Natural Science Foundation of China[30925041] ; National Natural Science Foundation of China[30901866] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program"[2009ZX09501-024-] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program"[2009ZX09301-001] ; CAS[KSCX2-YW-R-193]
WOS关键词	METASTATIC BREAST-CANCER ; IN-VIVO ; DELIVERY ; CHEMOTHERAPY ; EFFICACY ; PHARMACOKINETICS ; BIODISTRIBUTION ; NANOTOXICOLOGY ; CYTOTOXICITY ; FORMULATIONS
WOS研究方向	Science & Technology - Other Topics ; Toxicology
语种	英语
出版者	TAYLOR & FRANCIS LTD
WOS记录号	WOS:000296633100015
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278324]
专题	药物制剂研究中心上海中药现代化研究中心
通讯作者	Li, Yaping
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Natl Evaluat Ctr Toxicol Fertil Regulating Drugs, Shanghai, Peoples R China 3.Shanghai Inst Planned Parenthood Res, Shanghai, Peoples R China;
推荐引用方式 GB/T 7714	Gao, Yu,Yang, Rongfu,Zhang, Zhiwen,et al. Solid lipid nanoparticles reduce systemic toxicity of docetaxel: Performance and mechanism in animal[J]. NANOTOXICOLOGY,2011,5(4):636-649.
APA	Gao, Yu,Yang, Rongfu,Zhang, Zhiwen,Chen, Lingli,Sun, Zuyue,&Li, Yaping.(2011).Solid lipid nanoparticles reduce systemic toxicity of docetaxel: Performance and mechanism in animal.NANOTOXICOLOGY,5(4),636-649.
MLA	Gao, Yu,et al."Solid lipid nanoparticles reduce systemic toxicity of docetaxel: Performance and mechanism in animal".NANOTOXICOLOGY 5.4(2011):636-649.