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学科主题: 药学
题名:
Sublingual delivery of insulin: Effects of enhancers on the mucosal lipid fluidity and protein conformation, transport, and in vivo hypoglycemic activity
作者: Cui, CY; Lu, WL; Xiao, L; Zhang, SQ; Huang, YB; Li, SL; Zhang, RJ; Wang, GL; Zhang, X; Zhang, Q
关键词: insulin ; enhancing mechanism ; transport ; hypoglycemic activity ; sublingual delivery
刊名: BIOLOGICAL & PHARMACEUTICAL BULLETIN
发表日期: 2005-12-01
卷: 28, 期:12, 页:2279-2288
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]: CELL ADHERENS JUNCTIONS ; TIGHT JUNCTIONS ; BUCCAL EPITHELIUM ; BARRIER FUNCTION ; DRUG-DELIVERY ; CULTURE MODEL ; SHEAR-STRESS ; TR146 CELLS ; VITRO MODEL ; ABSORPTION
英文摘要:

The purposes of this study were to evaluate effects of enhancers for sublingual delivering insulin on the mucosal lipid fluidity and protein conformation, transport, and in vivo hypoglycemic activity in normal rats. The effects on sublingual mucosa, and aggregation states of insulin were estimated using fluorescence polarization, and circular dichroism method, respectively. The human immortalized oral epithelial cell monolayer was used for evaluating transport of insulin. Hydroxylpropyl-beta-cyclodextrin (HP-P-CD), chitosan, polyethylene-polyp ropylene glycol, polyoxyethylene lauryl ether, polysorbate 80, egg lecithin, or oleic acid, was used as a penetration enhancer, respectively. The fluidity of sublingual mucosal lipid was markedly reduced by these enhancers excluding polysorbate 80, and the secondary structure of the mucosal proteins was also influenced by these enhancers. The hexamers of insulin were dissociated to monomers only by chitosan, polyoxyethylene lauryl ether, and egg lecithin. Nonetheless, plasma glucose levels in normal rats were significantly lowered after sublingual administration of insulin with an enhancer compared with those without an enhancer at the same time-point. The enhancing effects may be due to one or multiple factors: increasing the mucosal lipid fluidity, directly loosing the tight junction of epithelia, and dissociating the hexamers of insulin to monomers. Among these, the opened tight junction may correlate most with the enhancing effect in the mucosal permeability. Because the aggregates of insulin exist, the dissociation of the aggregates by an enhancer would benefit the permeability.

语种: 英语
WOS记录号: WOS:000234096100022
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62002
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, Sch Basic Med Sci, Beijing 100083, Peoples R China
2.Peking Univ, Sch Stomatol, Beijing 100083, Peoples R China
3.Peking Univ, Sch Pharmaceut Sci, Beijing 100083, Peoples R China
4.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100083, Peoples R China

Recommended Citation:
Cui, CY,Lu, WL,Xiao, L,et al. Sublingual delivery of insulin: Effects of enhancers on the mucosal lipid fluidity and protein conformation, transport, and in vivo hypoglycemic activity[J]. BIOLOGICAL & PHARMACEUTICAL BULLETIN,2005,28(12):2279-2288.
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