國家衛生研究院 NHRI:Item 3990099045/9603
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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 (Ca2 +) has a crucial role in maintaining the intestinal protease activity and in forming the apical junction complex (AJC) that preserves epithelial barrier function. Ethylene glycol tetraacetic acid (EGTA) is a Ca2 +-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 Ca2 + ions could be specifically chelated to the nitrogen atoms, ether oxygen atoms, and carboxylate oxygen atoms in [Ca(EGTA)]2 − anions. By chelating Ca2 +, 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 123I-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
    日期: 2016-02
    關聯: Nanomedicine: Nanotechnology, Biology and Medicine. 2016 Feb;12(2):463.
    Link to: http://dx.doi.org/10.1016/j.nano.2015.12.050
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1549-9634&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000373923400067
    显示于类别:[陳炯東] 會議論文/會議摘要

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