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首页> 外文期刊>ACS applied materials & interfaces >Surface Coating Approach to Overcome Mucosal Entrapment of DNA Nanoparticles for Oral Gene Delivery of Glucagon-like Peptide 1
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Surface Coating Approach to Overcome Mucosal Entrapment of DNA Nanoparticles for Oral Gene Delivery of Glucagon-like Peptide 1

机译：克服DNA纳米颗粒的表面涂层方法，用于胰高血糖素肽的口服基因递送1

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摘要

Oral delivery of nucleic acid therapy is a promising strategy in treating various diseases because of its higher patient compliance and therapeutic efficiency compared to parenteral routes of administration. However, its success has been limited by the low transfection efficiency resulting from nucleic acid entrapment in the mucus layer and epithelial barrier of the gastrointestinal (GI) tract. Herein, we describe an approach to overcome this phenomenon and improve oral DNA delivery in the context of treating type II diabetes (T2D). Linear PEI (lPEI) was used as a carrier to form complexes with plasmid DNA encoding glucagon-like peptide 1 (GLP-1), a common target in T2D treatments. These nanoparticles were then coated with a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dimyristoyl-rac-glycero-3-methoxy poly(ethylene glycol)-2000 (DMG-PEG) to render the nanoparticle surface hydrophilic and electrostatically neutral. The surface-modified lPEI/DNA nanoparticles showed higher diffusivity and transport in the mucus layer of the GI tract and mediated high levels of transfection efficiency in vitro and in vivo. Moreover, these modified nanoparticles demonstrated high levels of GLP-1 expression for more than 24 h in the liver, lungs, and intestine in a T2D murine model after a single dose, as well as controlled blood glucose levels within a normal range for at least 18 h with repeatable therapeutic effects upon multiple dosages. Taken together, this work demonstrates the feasibility of an oral plasmid DNA delivery approach in the treatment of T2D through a facile surface modification to improve the mucus permeability and delivery efficiency of the nanoparticles.
机译：核酸治疗的口服递送是治疗各种疾病的有前途的策略，因为它与肠胃外给药途径相比其更高的患者依从性和治疗效率。然而，它的成功受到粘液层中核酸夹带的低转染效率的限制，胃肠道（GI）道的上皮屏障。在此，我们描述了一种克服这种现象的方法，并在治疗II型糖尿病（T2D）的背景下改善口服DNA递送。用线性PEI（LPEI）用作载体以形成与编码胰高血糖素肽1（GLP-1）的质粒DNA的复合物，在T2D处理中的常见靶标。然后将这些纳米颗粒涂覆有1,2-二硫代酰-N-甘油-3-普华啉（DPPC）和1,2-DiMyrestoyl-Rac-Glycetro-3-甲氧基聚（乙二醇）-2000的混合物（DMG-PEG ）使纳米颗粒表面亲水和静电中性。表面改性的LPEI / DNA纳米颗粒在GI沟槽的粘液层中显示出更高的扩散和转运，并在体外介导高水平的转染效率。此外，这些改性纳米颗粒在单剂量后，在T2D鼠模型中的肝脏，肺和肠道中显示出高水平的GLP-1表达超过24小时，并且至少在常规范围内控制血糖水平18小时，具有多种剂量的可重复治疗效果。在一起，这项工作展示了口服质粒DNA递送方法在处理T2D的过程中通过容易表面改性来改善纳米颗粒的粘液渗透性和输送效率。

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  • 来源
    《ACS applied materials & interfaces》 |2019年第33期|共11页
  • 作者

    Nie Tianqi; He Zhiyu; Zhou Yang; Zhu Jinchang; Chen Kuntao; Liu Lixin; Leong Kam W.; Mao Hai-Quan; Chen Yongming;

  • 作者单位

    Sun Yat Sen Univ Sch Mat Sci &

    Engn Guangzhou 510275 Guangdong Peoples R China;

    Sun Yat Sen Univ Sch Mat Sci &

    Engn Guangzhou 510275 Guangdong Peoples R China;

    Johns Hopkins Univ Whiting Sch Engn Dept Mat Sci &

    Engn Baltimore MD 21218 USA;

    Johns Hopkins Univ Whiting Sch Engn Dept Mat Sci &

    Engn Baltimore MD 21218 USA;

    Johns Hopkins Univ Whiting Sch Engn Dept Mat Sci &

    Engn Baltimore MD 21218 USA;

    Sun Yat Sen Univ Sch Mat Sci &

    Engn Guangzhou 510275 Guangdong Peoples R China;

    Sun Yat Sen Univ Sch Mat Sci &

    Engn Guangzhou 510275 Guangdong Peoples R China;

    Sun Yat Sen Univ Sch Mat Sci &

    Engn Guangzhou 510275 Guangdong Peoples R China;

    Sun Yat Sen Univ Sch Mat Sci &

    Engn Guangzhou 510275 Guangdong Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学工业;
  • 关键词

    oral delivery; nucleic acid therapy; GLP-1; type II diabetes; surface coating;

    机译：口服递送;核酸治疗;GLP-1;II型糖尿病;表面涂层;

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