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Increase of the pharmacological and pharmacokinetic efficacy of negatively charged polypeptide recombinant hirudin in rats via parenteral route by association with cationic liposomes
Meng, Meng; Liu, Yu; Wang, Yi-Bo; Wang, Jian-Cheng; Zhang, Hua; Wang, Xue-Qing; Zhang, Xuan; Lu, Wan-Liang; Zhang, Qiang
关键词recombinant hirudin cationic liposomes sustained release entrapment in vivo studies
刊名JOURNAL OF CONTROLLED RELEASE
2008-06-04
DOI10.1016/j.jconrel.2008.03.001
128期:2页:113-119
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]GENE-TRANSFER ; IN-VITRO ; PHASE-I ; DELIVERY ; PROTEIN ; CELLS ; COMPLEXES ; CARCINOMA ; INSULIN ; PHARMACODYNAMICS
英文摘要

Two biodegradable cationic lipids, stearylamine and DC-Chol, were chosen to investigate the effect of cationic lipids on the in vitro and in vivo characteristics of hydrophilic proteins or peptides of low isoelectric point. Thrombin inhibitor recombinant hirudin variant-2 (rHV2) was selected as the model drug. The cationic lipids were found to achieve higher entrapment efficiency of rHV2 in liposomes than zwitterionic lipids. The positively charged liposomes became less positive and relatively stable in serum after loading rHV2. The cationic liposomes induced sustained release of rHV2 in the presence of plasma, significantly prolonged the antithrombotic efficacy and plasma level of rHV2 after intravenous injection in rats in comparison with neutral lipid liposomes, especially for stearylamine group. Both clotting times correlated well with plasma rHV2 levels. No serious adverse events were observed and physical state of rats was satisfactory for all the formulations. Electrostatic interaction between negative charge of rHV2 and cationic liposomes was confirmed and it might affect all the characteristics of rHV2 loaded cationic vehicles. The findings suggest that cationic liposomes may be a potential sustained-release delivery system for parenteral administration of hydrophilic proteins or peptides with low isoelectric point to prolong efficacy and improve bioavailability. (C) 2008 Elsevier B.V. All rights reserved.

语种英语
WOS记录号WOS:000256955200002
引用统计
被引频次:16[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/400002259/60459
专题北京大学药学院
北京大学药学院_药剂学系
作者单位Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100083, Peoples R China
推荐引用方式
GB/T 7714
Meng, Meng,Liu, Yu,Wang, Yi-Bo,et al. Increase of the pharmacological and pharmacokinetic efficacy of negatively charged polypeptide recombinant hirudin in rats via parenteral route by association with cationic liposomes[J]. JOURNAL OF CONTROLLED RELEASE,2008,128(2):113-119.
APA Meng, Meng.,Liu, Yu.,Wang, Yi-Bo.,Wang, Jian-Cheng.,Zhang, Hua.,...&Zhang, Qiang.(2008).Increase of the pharmacological and pharmacokinetic efficacy of negatively charged polypeptide recombinant hirudin in rats via parenteral route by association with cationic liposomes.JOURNAL OF CONTROLLED RELEASE,128(2),113-119.
MLA Meng, Meng,et al."Increase of the pharmacological and pharmacokinetic efficacy of negatively charged polypeptide recombinant hirudin in rats via parenteral route by association with cationic liposomes".JOURNAL OF CONTROLLED RELEASE 128.2(2008):113-119.
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