國家衛生研究院 NHRI:Item 3990099045/10916
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    题名: Multifunctional nanoparticles for oral protein drug delivery
    作者: Chuang, EY;Lin, KJ;Su, FY;Mi, FL;Chen, CT;Juang, JH;Sung, HW
    贡献者: Institute of Biotechnology and Pharmaceutical Research
    摘要: Calcium (Ca 2+ ) has a crucial role in maintaining the intestinal protease activity and in forming the apical junctional complex (AJC) that preserves epithelial barrier function. Ethylene glycol tetraacetic acid (EGTA) is a Ca 2+ -specific chelating agent. To maintain the concentration of this chelator in areas where enzyme inhibition and paracellular permeation enhancement are needed, this study synthesized a poly(γ-glutamic acid)-EGTA conjugate (γPGA-EGTA) to form nanoparticles (NPs) with chitosan (CS) for oral insulin delivery. Results of our molecular dynamic (MD) simulations indicate that Ca 2+ ions could be specifically chelated to the nitrogen atoms, ether oxygen atoms, and carboxylate oxygen atoms in [Ca(EGTA)] 2– anions. By chelating Ca 2+ , γPGA-EGTA conferred a significant insulin protection effect against proteases in intestinal tracts isolated from rats. Additionally, calcium depletion by γPGA-EGTA could stimulate the endocytosis of AJC components in Caco-2 cell monolayers, which led to a reversible opening of AJCs and thus increased their paracellular permeability. Single-photon emission computed tomography images performed in the biodistribution study clearly show the 123 I-insulin orally delivered by CS/γPGA-EGTA NPs in the heart, aorta, renal cortex, renal pelvis and liver, which ultimately produced a significant and prolonged hypoglycemic effect in diabetic rats. The above results confirm that this γPGA-EGTA conjugate is a promising candidate for oral insulin delivery.
    日期: 2016-10
    關聯: Diabetes Research and Clinical Practice. 2016 Oct;120(Suppl. 1):S19.
    Link to: http://dx.doi.org/10.1016/S0168-8227(16)30928-7
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0168-8227&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000416113300058
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