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学科主题: 药学
题名:
The use of polyion complex micelles to enhance the oral delivery of salmon calcitonin and transport mechanism across the intestinal epithelial barrier
作者: Li, Na1; Li, Xin-Ru1; Zhou, Yan-Xia1; Li, Wen-Jing1; Zhao, Yong1; Ma, Shu-Jin1; Li, Jin-Wen1; Gao, Ya-Jie1; Liu, Yan1; Wang, Xing-Lin2; Yin, Dong-Dong2
关键词: Salmon calcitonin ; Polyion complex micelles ; Monomethoxy poly(ethylene glycol)-grafted-alginic acid ; Transport mechanism ; Oral drug delivery
刊名: BIOMATERIALS
发表日期: 2012-12-01
DOI: 10.1016/j.biomaterials.2012.08.047
卷: 33, 期:34, 页:8881-8892
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Engineering, Biomedical ; Materials Science, Biomaterials
研究领域[WOS]: Engineering ; Materials Science
关键词[WOS]: IN-VIVO CHARACTERIZATION ; BLOCK-COPOLYMER ; TARGETED DELIVERY ; ABSORPTION ; VITRO ; ACID) ; PROLIPOSOMES ; DERIVATIVES ; EXCIPIENTS ; EFFICACY
英文摘要:

The objective of the present study was to demonstrate the effect of polyanionic copolymer mPEG-grafted-alginic acid (mPEG-g-AA)-based polyion complex (PIC) micelles on enhancing the oral absorption of salmon calcitonin (sCT) in vivo and in vitro and identify the transepithelial transport mechanism of PIC micelles across the intestinal barrier. mPEG-g-AA was first successfully synthesized and characterized in cytotoxicity. The PIC micelles were approximately of 72 nm in diameter with a narrow distribution. The extremely significant enhancement of hypocalcemia efficacy of sCT-loaded PIC micelles in rats was evidenced by intraduodenal administration in comparison with sCT solution. The presence of mPEG-grafted-chitosan in PIC micelles had no favorable effect on this action in the referred content. In the Caco-2 transport studies, PLC micelles could significantly increase the permeability of sCT across Caco-2 monolayers without significantly affecting transepithelial electrical resistance values during the transport study. No evident alterations in the F-actin cytoskeleton were detected by confocal microscope observation following treatment of the cell monolayers with PIC micelles, which further certified the incapacity of PIC micelles to open the intercellular tight junctions. In addition, TEM observations showed that the intact PLC micelles were transported across the everted gut sac. These suggested that the transport of PIC micelles across Caco-2 cell monolayers involve a predominant transcytosis mechanism via endocytosis rather than paracellular pathway. Furthermore, PIC micelles were localized in both the cytoplasm and the nuclei observed by CLSM. Therefore, PLC micelles might be a potentially applicable tool for enhancing the oral absorption of cationic peptide and protein drugs. (C) 2012 Elsevier Ltd. All rights reserved.

语种: 英语
所属项目编号: 81172990 ; 2009CB930300 ; BMU20110263
项目资助者: National Natural Science Foundation of China ; National Key Science Research Program of China (973 program) ; Innovation Team of Ministry of Education ; State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research
WOS记录号: WOS:000310390100014
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58661
Appears in Collections:北京大学药学院_药剂学系_期刊论文

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作者单位: 1.Peking Univ, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100191, Peoples R China
2.Tianjin Inst Pharmaceut Res, State Key Lab Drug Delivery Technol & Pharmacokin, Tianjin 300193, Peoples R China

Recommended Citation:
Li, Na,Li, Xin-Ru,Zhou, Yan-Xia,et al. The use of polyion complex micelles to enhance the oral delivery of salmon calcitonin and transport mechanism across the intestinal epithelial barrier[J]. BIOMATERIALS,2012,33(34):8881-8892.
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