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学科主题: 药学
题名:
Nasal recombinant hirudin-2 delivery: Absorption and its mechanism in vivo and in vitro studies
作者: Zhang, YJ; Zhang, Q; Sun, YK; Sun, JN; Wang, XL; Chen, MX
关键词: recombinant hirudin-2 (rHV2) ; nasal absorption ; mechanism ; degradation
刊名: BIOLOGICAL & PHARMACEUTICAL BULLETIN
发表日期: 2005-12-01
卷: 28, 期:12, 页:2263-2267
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: DRUG-DELIVERY ; ENHANCERS ; INSULIN ; RAT ; INVITRO ; MUCOSA
英文摘要:

The objective of this study was to investigate the feasibility of systemic absorption of recombinant hirudin-2 (rHV2) by nasal delivery, and its possible absorption mechanism. The degradation of rHV2 in the nasal tissue homogenate and extracts of mucosae of rabbit, as well as the degradation inhibition of enzyme inhibitor (bacitracin) was evaluated. The bioavailability of rHV2 and the improvement with enhancers, after nasal administration in rats was investigated. For further understanding of the transport and uptake characteristics of rHV2, in vitro transport experiment under various conditions using diffusion chamber technique in excised rabbit nasal epithelium was performed. It was found that rHV2 underwent rapid degradation in rabbit nasal homogenate, but it was more stable in the extracts of nasal mucosae surface. Bacitracin was able to inhibit the degradation of rHV2 to certain extent. rHV2 was detected in the rat plasma by chromogenic substrate assay after nasal administration and some enhancers also significantly increased the nasal absorption of rHV2. The transport and uptake of rHV2 across nasal epithelium was concentration-dependent and unsaturated, and was significantly inhibited by low temperature, NaN3, DNP and colchicines, while was less affected by alteration of transport direction. These results demonstrate that the possible absorption mechanism of rHV2 by nasal mucosa appears to be associated with the endocytosis as well as passive diffusion process.

语种: 英语
WOS记录号: WOS:000234096100018
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57077
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Beijing Univ Trad Chinese Med, Dept Chinese Pharm, Beijing 100102, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Beijing 100083, Peoples R China

Recommended Citation:
Zhang, YJ,Zhang, Q,Sun, YK,et al. Nasal recombinant hirudin-2 delivery: Absorption and its mechanism in vivo and in vitro studies[J]. BIOLOGICAL & PHARMACEUTICAL BULLETIN,2005,28(12):2263-2267.
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