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Enhanced transport of nanocage stabilized pure nanodrug across intestinal epithelial barrier mimicking Listeria monocytogenes

文献类型：期刊论文

作者Xia, Dengning4; Tao, Jinsong3,4; He, Yuan2,4; Zhu, Quanlei4; Chen, Dan4; Yu, Miaorong4; Cui, Fude1; Gan, Yong4
刊名BIOMATERIALS
出版日期2015-01
卷号37页码:320-332
关键词Nanocrystals Nanocage Epithelial barrier Wheat germ agglutinin Goblet cells
ISSN号0142-9612
DOI10.1016/j.biomaterials.2014.10.038
文献子类Article
英文摘要Ligand grafted nanoparticles have been shown to enhance drug transport across epithelium barrier and are expected to improve drug delivery. However, grafting of these ligands to the surface of pure nanodrug, i.e., nanocrystals (NCs), is a critical challenge due to the shedding of ligands along with the stabilizer upon high dilution or dissolving of the drug. Herein, a non-sheddable nanocage-like stabilizer was designed by covalent cross-linking of poly(acrylic acid)-b-poly(methyl acrylate) on drug nanocrystal surface, and a ligand, wheat germ agglutinin (WGA), was successfully anchored to the surface of itraconazole (ITZ) NCs by covalent conjugation to the nanocage (WGA-cage-NCs). The cellular study showed that large amount of WGA-cage-NCs were adhered to Caco-2 cell membrane, and invaded into cells, resulting in a higher drug uptake than that of ordinary NCs (ONCs). After oral administration to rats, WGA-cage-NC were largely accumulated on the apical side of epithelium cells, facilitating drug diffusing across epithelium barrier. Interestingly, WGA-cage-NCs were capable of invading rat intestinal villi and reaching to lamina propria by transcytosis across goblet cells, which behaved like a foodborrie pathogen, Listeria monocytogenes. The WGA-cage-NCs showed an improved oral bioavailability, which was 17.5- and 2.41-folds higher than that of coarse crystals and ONCs, respectively. To our best knowledge, this may represent the first report that a functional ligand was successfully anchored to the surface of pure nanodrug by using a cage-like stabilizer, showing unique biological functions in gastrointestinal tract and having an important significance in oral drug delivery. (C) 2014 Elsevier Ltd. All rights reserved.
WOS关键词ORAL PEPTIDE DELIVERY ; IN-VIVO EVALUATION ; DRUG-DELIVERY ; POLYMERIC NANOPARTICLES ; BACTERIAL INVASION ; CELLULAR UPTAKE ; PARTICLE-SIZE ; NITRENDIPINE NANOCRYSTALS ; ANTICANCER DRUGS ; E-CADHERIN
资助项目National Natural Science Foundation of China[81202468] ; China Postdoctoral Science Foundations[2013M530219] ; China Postdoctoral Science Foundations[2014T70445] ; SA-SIBS Scholarship Program[00000000]
WOS研究方向Engineering ; Materials Science
语种英语
WOS记录号WOS:000346541100031
出版者ELSEVIER SCI LTD
源URL[http://119.78.100.183/handle/2S10ELR8/276781]  
专题药物制剂研究中心
通讯作者Gan, Yong
作者单位1.Shenyang Pharmaceut Univ, Sch Pharmaceut Sci, Dept Pharmaceut, Shenyang 110016, Peoples R China
2.Chongqing Med Univ, Sch Pharm, Dept Pharmaceut, Chongqing 400016, Peoples R China;
3.Nanchang Univ, Coll Med, Dept Pharm, Nanchang 330066, Peoples R China;
4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
推荐引用方式
GB/T 7714		 Xia, Dengning,Tao, Jinsong,He, Yuan,et al. Enhanced transport of nanocage stabilized pure nanodrug across intestinal epithelial barrier mimicking Listeria monocytogenes[J]. BIOMATERIALS,2015,37:320-332.
APA Xia, Dengning.,Tao, Jinsong.,He, Yuan.,Zhu, Quanlei.,Chen, Dan.,...&Gan, Yong.(2015).Enhanced transport of nanocage stabilized pure nanodrug across intestinal epithelial barrier mimicking Listeria monocytogenes.BIOMATERIALS,37,320-332.
MLA Xia, Dengning,et al."Enhanced transport of nanocage stabilized pure nanodrug across intestinal epithelial barrier mimicking Listeria monocytogenes".BIOMATERIALS 37(2015):320-332.

入库方式： OAI收割

来源：上海药物研究所

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