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首页> 外文期刊>Advanced Materials >A Noninvasive Gut-to-Brain Oral Drug Delivery System for Treating Brain Tumors
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A Noninvasive Gut-to-Brain Oral Drug Delivery System for Treating Brain Tumors

机译：一种治疗脑肿瘤的非侵袭性肠道口腔药物递送系统

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摘要

Most orally administered drugs fail to reach the intracerebral regions because of the intestinal epithelial barrier (IEB) and the blood-brain barrier (BBB), which are located between the gut and the brain. Herein, an oral prodrug delivery system that can overcome both the IEB and the BBB noninvasively is developed for treating gliomas. The prodrug is prepared by conjugating an anticancer drug on beta-glucans using a disulfide-containing linker. Following oral administration in glioma-bearing mice, the as-prepared prodrug can specifically target intestinal M cells, transpass the IEB, and be phagocytosed/hitchhiked by local macrophages (M phi). The M phi-hitchhiked prodrug is transported to the circulatory system via the lymphatic system, crossing the BBB. The tumor-overexpressed glutathione then cleaves the disulfide bond within the prodrug, releasing the active drug, improving its therapeutic efficacy. These findings reveal that the developed prodrug may serve as a gut-to-brain oral drug delivery platform for the well-targeted treatment of gliomas.
机译：由于肠上皮屏障（IEB）和血脑屏障（BBB）位于肠道和大脑之间，最口服给药的药物未能到达脑内区域。在此，可以开发出可克服IEB和BBB的口腔前药递送系统用于治疗胶质瘤。通过使用含二硫化物的接头在β-葡聚糖上缀合抗癌药物来制备前药。在含胶质瘤的小鼠中口服施用后，所制备的前药可以特异性靶向肠M细胞，过度通过局部巨噬细胞（MPHI）吞噬/携带吞噬/携带。 M phi-hitchhiked prodrug通过淋巴系统运输到循环系统，穿过BBB。然后肿瘤过滤的谷胱甘肽在前药中的二硫键，释放活性药物，提高其治疗效果。这些发现表明，发育的前药可以作为脑脑脑脑部口服药物递送平台，用于嗜好的胶质瘤的良好治疗。

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  • 来源
    《Advanced Materials》 |2021年第34期|2100701.1-2100701.11|共11页
  • 作者

    Miao Yang-Bao; Chen Kuan-Hung; Chen Chiung-Tong; Mi Fwu-Long; Lin Yu-Jung; Chang Yen; Chiang Chi-Shiun; Wang Jui-To; Lin Kun-Ju; Sung Hsing-Wen;

  • 作者单位

    Natl Tsing Hua Univ Dept Chem Engn Hsinchu 30013 Taiwan|Natl Tsing Hua Univ Frontier Res Ctr Fundamental & Appl Sci Matters Hsinchu 30013 Taiwan;

    Natl Tsing Hua Univ Dept Chem Engn Hsinchu 30013 Taiwan|Natl Tsing Hua Univ Frontier Res Ctr Fundamental & Appl Sci Matters Hsinchu 30013 Taiwan;

    Natl Hlth Res Inst Inst Biotechnol & Pharmaceut Res Miaoli 35053 Taiwan;

    Taipei Med Univ Coll Med Sch Med Dept Biochem & Mol Cell Biol Taipei 23142 Taiwan;

    Acad Sinica Res Ctr Appl Sci Taipei 11529 Taiwan;

    Buddhist Tzu Chi Med Fdn Taipei Tzu Chi Hosp Hualien 97004 Taiwan|Tzu Chi Univ Sch Med Hualien 97004 Taiwan;

    Natl Tsing Hua Univ Dept Biomed Engn & Environm Sci Hsinchu 30013 Taiwan;

    Taipei Vet Gen Hosp Dept Neurosurg Neurol Inst Taipei 11217 Taiwan|Natl Yang Ming Univ Inst Brain Sci Taipei 11221 Taiwan;

    Linkou Chang Gung Mem Hosp Dept Nucl Med Taoyuan 33302 Taiwan|Linkou Chang Gung Mem Hosp Mol Imaging Ctr Taoyuan 33302 Taiwan|Chang Gung Univ Dept Med Imaging & Radiol Sci Taoyuan 33302 Taiwan;

    Natl Tsing Hua Univ Dept Chem Engn Hsinchu 30013 Taiwan|Natl Tsing Hua Univ Frontier Res Ctr Fundamental & Appl Sci Matters Hsinchu 30013 Taiwan;

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  • 正文语种 eng
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  • 关键词

    blood-brain barrier; glioma; intestinal epithelial barrier; macrophage hitchhiking; prodrugs;

    机译：血脑屏障;胶质瘤;肠道上皮屏障;巨噬细胞搭便车;前药;

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