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Permeation-enhancing effects of chitosan formulations on recombinant hirudin-2 by nasal delivery in vitro and in vivo
Zhang, YJ1; Ma, CH1; Lu, WL1; Zhang, X1; Wang, XL1; Sun, JN1; Zhang, Q1
关键词Nasal Absorption Hirudin Chitosan Formulation Permeability Bioavailability Enhancer Ciliotoxicity
刊名ACTA PHARMACOLOGICA SINICA
2005-11-01
DOI10.1111/j.1745-7254.2005.00174.x
26期:11页:1402-1408
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]CACO-2 CELL MONOLAYERS ; ABSORPTION ENHANCERS ; DRUG ; CYCLODEXTRINS ; TRANSPORT ; MECHANISM ; SYSTEM ; RATS
英文摘要

Aim: To investigate the enhancing effects of chitosan with or without enhancers on nasal recombinant hirudin-2 (rHV2) delivery in vitro and in vivo, and to evaluate the ciliotoxicity of these formulations. Methods: The permeation-enhancing effect of various chitosan formulations was estimated by using the permeation coefficient of fluorescein isothiocyanate recombinant hirudin-2 (FITC-rHV2) across the excited rabbit nasal epithelium in vitro. The effect was further evaluated by measuring the blood concentration level after nasal absorption of FITC-rHV2 in rats. The mucosal ciliotoxicity of different formulations was evaluated with an in situ toad palate model. Results: Chitosan at a concentration of 0.5% with or without various enhancers significantly increased the permeability coefficient (P) and relative bioavailability (Fr) of FITC-rHV2 compared with the blank control. The addition of 1% sodium dodecylsulfate, 5% Brij35,5% Tween 80,1.5% menthol, 1% glycyrrhizic acid monoammonium salt (GAM) or 4% Azone into the 0.5% chitosan solution resulted in a further increase in absorption (P < 0.05) compared with 0.5% chitosan alone. But co-administration of chitosan with 5% hydroxyl-propyl-beta-cyclodextrin (HP-beta-CD), 5% lecithin or 0.1% ethylenediaminetetraacetic acid (EDTA) was not more effective than using the 0.5% chitosan solution alone. Chitosan alone and with 5% HP-P-CD, 0.1% EDTA, 1% GAM or 5%Tween80 was relatively less ciliotoxic. Conclusion: Chitosan with or without some enhancers was able to effectively promote the nasal absorption of recombinant hirudin, while not resulting in severe mucosal ciliotoxicity. A chitosan formulation system would be a useful approach for the nasal delivery of recombinant hirudin.

语种英语
WOS记录号WOS:000233209800019
引用统计
被引频次:19[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/400002259/52112
专题北京大学药学院
北京大学药学院_药剂学系
北京大学第三临床医学院_妇产科
作者单位1.Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Beijing 100083, Peoples R China
2.Beijing Univ Tradit Chinese Med, Dept Chinese Pharm, Beijing 100102, Peoples R China
推荐引用方式
GB/T 7714
Zhang, YJ,Ma, CH,Lu, WL,et al. Permeation-enhancing effects of chitosan formulations on recombinant hirudin-2 by nasal delivery in vitro and in vivo[J]. ACTA PHARMACOLOGICA SINICA,2005,26(11):1402-1408.
APA Zhang, YJ.,Ma, CH.,Lu, WL.,Zhang, X.,Wang, XL.,...&Zhang, Q.(2005).Permeation-enhancing effects of chitosan formulations on recombinant hirudin-2 by nasal delivery in vitro and in vivo.ACTA PHARMACOLOGICA SINICA,26(11),1402-1408.
MLA Zhang, YJ,et al."Permeation-enhancing effects of chitosan formulations on recombinant hirudin-2 by nasal delivery in vitro and in vivo".ACTA PHARMACOLOGICA SINICA 26.11(2005):1402-1408.
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