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学科主题: 药学
题名:
Novel thermo-sensitive hydrogel system with paclitaxel nanocrystals: High drug-loading, sustained drug release and extended local retention guaranteeing better efficacy and lower toxicity
作者: 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
发表日期: 2014-01-28
DOI: 10.1016/j.jconrel.2013.10.026
卷: 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
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
项目资助者: National Natural Science Foundation of China ; National Basic Research Program of China ; Innovation Team of Ministry of Education
WOS记录号: WOS:000329964500019
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61952
Appears in Collections:北京大学药学院_期刊论文

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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

Recommended Citation:
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.
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