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Novel thermo-sensitive hydrogel system with paclitaxel nanocrystals: High drug-loading, sustained drug release and extended local retention guaranteeing better efficacy and lower toxicity
Lin, Zhiqiang1,2; Gao, Wei1,2; Hu, Hongxiang1,2; Ma, Kun3; He, Bing1,2; Dai, Wenbing1,2; Wang, Xueqing2; Wang, Jiancheng2; Zhang, Xuan2; Zhang, Qiang2
关键词Nanocrystals Thermo-sensitive gel Drug release Intratumoral delivery Anti-tumor effect
刊名JOURNAL OF CONTROLLED RELEASE
2014-01-28
DOI10.1016/j.jconrel.2013.10.026
174页:161-170
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
资助者National Natural Science Foundation of China ; National Basic Research Program of China ; Innovation Team of Ministry of Education ; National Natural Science Foundation of China ; National Basic Research Program of China ; Innovation Team of Ministry of Education
研究领域[WOS]Chemistry ; Pharmacology & Pharmacy
关键词[WOS]HIGH-DOSE CHEMOTHERAPY ; BREAST-CANCER ; OVARIAN-CANCER ; IN-VIVO ; CONTROLLED DELIVERY ; POLYMERIC MICELLES ; PLURONIC(R) F127 ; NANOPARTICLES ; CYTOTOXICITY ; FORMULATION
英文摘要

As a sustained-release drug depot for localized cancer treatment, in situ thermo-sensitive hydrogel has attracted increasing interests. However, it is currently a big challenge to achieve high drug-loading, sustained and stable drug release, as well as long-term local drug retention simultaneously. We hypothesized that this goal could be accomplished by incorporating the nanocrystals (NCs) of a hydrophobic drug, such as paclitaxel (PTX) into the thermo-sensitive hydrogel (Gel). Hence, a PTX-NCs-Gel system has been constructed with thermosensitive Pluronic F127, using PTX-NCs and Taxol (R) as the controls. Besides, near infra-red agent DiR was used to prepare PTX/DiR hybrid NCs and PTX/DiR hybrid NCs-Gel as well. As a result, this hydrogel system could achieve a high drug loading of PTX up to 3 mg/ml while stabilize the particle size of PTX-NCs significantly compared with PTX-NCs alone. There was no obvious interaction between PTX-NCs and F127. Obviously, PTX/DiR hybrid NCs- Gel presented better localized retention capacity and a much longer retention time in murine 4T1 tumor than PTX/DiR hybrid NCs and Cremophor/ethanol solubilized DiR in vivo. With a linear elimination, over 10% of PTX still remained inside of mouse 4T1 tumor 20 days after intratumoral dosing of PTX-NCs-Gel. Importantly, PTX-NCs exhibited comparable cytotoxity against 4T1 and MCF-7 cells in vitro compared with Taxol (R), which could ensure the efficacy of PTX-NCs-Gel. After intratumoral injection, PTX-NCs-Gel was found to be the most effective among all PTX formulations in the 4T1 and MCF-7 tumor-bearing mice models, with much lower system toxicity than Taxol (R). In general, it is believed that the novel thermo-sensitive hydrogel system prepared in this study with PTX-NCs affords high drug-loading, sustained and stable drug release, as well as extended drug retention inside of tumor, which results in better therapy and lower toxicity. (C) 2013 Elsevier B.V. All rights reserved.

语种英语
所属项目编号81130059 ; 81273456 ; 2009CB930300 ; BMU20110263
资助者National Natural Science Foundation of China ; National Basic Research Program of China ; Innovation Team of Ministry of Education ; National Natural Science Foundation of China ; National Basic Research Program of China ; Innovation Team of Ministry of Education
WOS记录号WOS:000329964500019
引用统计
被引频次:59[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61952
专题北京大学药学院
作者单位1.State Food & Drug Adm, Ctr Drug Evaluat, Beijing 100038, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
3.Peking Univ, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Lin, Zhiqiang,Gao, Wei,Hu, Hongxiang,et al. Novel thermo-sensitive hydrogel system with paclitaxel nanocrystals: High drug-loading, sustained drug release and extended local retention guaranteeing better efficacy and lower toxicity[J]. JOURNAL OF CONTROLLED RELEASE,2014,174:161-170.
APA Lin, Zhiqiang.,Gao, Wei.,Hu, Hongxiang.,Ma, Kun.,He, Bing.,...&Zhang, Qiang.(2014).Novel thermo-sensitive hydrogel system with paclitaxel nanocrystals: High drug-loading, sustained drug release and extended local retention guaranteeing better efficacy and lower toxicity.JOURNAL OF CONTROLLED RELEASE,174,161-170.
MLA Lin, Zhiqiang,et al."Novel thermo-sensitive hydrogel system with paclitaxel nanocrystals: High drug-loading, sustained drug release and extended local retention guaranteeing better efficacy and lower toxicity".JOURNAL OF CONTROLLED RELEASE 174(2014):161-170.
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