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学科主题: 药学
题名:
Controlled delivery of recombinant hirudin based on thermo-sensitive Pluronic (R) F127 hydrogel for subcutaneous administration: In vitro and in vivo characterization
作者: Liu, Yu; Lu, Wan-Liang; Wang, Han-Cheng; Zhang, Xuan; Zhang, Hua; Wang, Xue-Qing; Zhou, Tian-Yan; Zhang, Qiang
关键词: pluronics ; controlled drug release ; recombinant hirudin ; anticoagulant ; bioavailability ; interaction
刊名: JOURNAL OF CONTROLLED RELEASE
发表日期: 2007-02-26
DOI: 10.1016/j.jconrel.2006.11.024
卷: 117, 期:3, 页:387-395
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]: BLOCK-COPOLYMER SOLUTIONS ; POLOXAMER 407 GELS ; CONTROLLED-RELEASE ; INTRAPERITONEAL INJECTION ; AQUEOUS-SOLUTIONS ; F-127 GELS ; GELATION ; FORMULATIONS ; LIDOCAINE ; PHARMACOKINETICS
英文摘要:

Here we investigated thermo-sensitive Pluronic((R)) F127 (PF127) hydrogel for the controlled release of peptide and protein drugs after subcutaneous injection, using an antithrombotic polypeptide, recombinant hirudin variant-2 (rHV2), as the model drug. The in vitro release experiment performed with a membrane-less model at 37 degrees C showed that the release of antithrombotic activity of rHV2 from PF127 gel followed zero-order kinetics and correlated well with the weight percentage of PF127 dissolved, indicating a dissolution-controlled release mechanism. The in vivo result obtained after subcutaneous injection of rHV2-loaded PF127 gel in normal rats demonstrated that PF127 gel improved the bioavailability, prolonged the antithrombotic effect of rHV2, and induced detectable plasma rHV2 concentration for a longer time in comparison with rHV2 aqueous solution. Differential scanning calorimetry, dynamic light scattering and Fourier transform infrared spectroscopy provided evidence of the interaction between PF127 and rHV2, but such interaction was unlikely to interfere the feasibility of this drug delivery system. Our current in vitro and in vivo study suggested that PF127 gel may be useful as an injectable delivery vehicle for peptides and proteins with short half-lives to prolong their therapeutic effect, increase their bioavailability and improve the clinic outcome. (c) 2006 Elsevier B.V All rights reserved.

语种: 英语
WOS记录号: WOS:000244928100011
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58491
Appears in Collections:北京大学药学院_药剂学系_期刊论文

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作者单位: Peking Univ, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100083, Peoples R China

Recommended Citation:
Liu, Yu,Lu, Wan-Liang,Wang, Han-Cheng,et al. Controlled delivery of recombinant hirudin based on thermo-sensitive Pluronic (R) F127 hydrogel for subcutaneous administration: In vitro and in vivo characterization[J]. JOURNAL OF CONTROLLED RELEASE,2007,117(3):387-395.
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