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Controlled delivery of recombinant hirudin based on thermo-sensitive Pluronic (R) F127 hydrogel for subcutaneous administration: In vitro and in vivo characterization
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
2007-02-26
DOI10.1016/j.jconrel.2006.11.024
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
引用统计
被引频次:101[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/400002259/58491
专题北京大学药学院_药剂学系
作者单位Peking Univ, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100083, Peoples R China
推荐引用方式
GB/T 7714
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.
APA Liu, Yu.,Lu, Wan-Liang.,Wang, Han-Cheng.,Zhang, Xuan.,Zhang, Hua.,...&Zhang, Qiang.(2007).Controlled delivery of recombinant hirudin based on thermo-sensitive Pluronic (R) F127 hydrogel for subcutaneous administration: In vitro and in vivo characterization.JOURNAL OF CONTROLLED RELEASE,117(3),387-395.
MLA Liu, Yu,et al."Controlled delivery of recombinant hirudin based on thermo-sensitive Pluronic (R) F127 hydrogel for subcutaneous administration: In vitro and in vivo characterization".JOURNAL OF CONTROLLED RELEASE 117.3(2007):387-395.
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