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学科主题: 药学
题名:
Permeation-enhancing effects of chitosan formulations on recombinant hirudin-2 by nasal delivery in vitro and in vivo
作者: 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
发表日期: 2005-11-01
DOI: 10.1111/j.1745-7254.2005.00174.x
卷: 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
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52112
Appears in Collections:北京大学药学院_期刊论文

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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

Recommended Citation:
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.
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