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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier
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Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier

机译:可快速降解人类粘液屏障的可生物降解的聚合物纳米颗粒

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摘要

Protective mucus coatings typically trap and rapidly remove foreign particles from the eyes, gastrointestinal tract, airways, nasopharynx, and female reproductive tract, thereby strongly limiting opportunities for controlled drug delivery at mucosal surfaces. No synthetic drug delivery system composed of biodegradable polymers has been shown to penetrate highly viscoelastic human mucus, such as non-ovulatory cervicovaginal mucus, at a significant rate. We prepared nanoparticles composed of a biodegradable diblock copolymer of poly(sebacic acid) and poly(ethylene glycol) (PSA-PEG), both of which are routinely used in humans. In fresh undiluted human cervicovaginal mucus (CVM), which has a bulk viscosity approximately 1,800-fold higher than water at low shear, PSA-PEG nanoparticles diffused at an average speed only 12-fold lower than the same particles in pure water. In contrast, similarly sized biodegradable nanoparticles composed of PSA or poly(lactic-co-glycolic acid) (PLGA) diffused at least 3,300-fold slower in CVM than in water. PSA-PEG particles also rapidly penetrated sputum expectorated from the lungs of patients with cystic fibrosis, a disease characterized by hyperviscoelastic mucus secretions. Rapid nanoparticle transport in mucus is made possible by the efficient partitioning of PEG to the particle surface during formulation. Biodegradable polymeric nanoparticles capable of overcoming human mucus barriers and providing sustained drug release open significant opportunities for improved drug and gene delivery at mucosal surfaces.
机译:保护性粘液涂层通常会从眼睛,胃肠道,气道,鼻咽和女性生殖道中捕获并迅速清除异物,从而极大地限制了在粘膜表面进行药物控制的机会。没有显示出由可生物降解的聚合物组成的合成药物递送系统以很高的速率穿透高粘弹性的人类黏液,例如非排卵性宫颈阴道黏液。我们制备了由聚(癸二酸)和聚(乙二醇)(PSA-PEG)可生物降解的二嵌段共聚物组成的纳米颗粒,这两种纳米颗粒均常用于人类。在新鲜的未稀释人宫颈阴道粘液(CVM)中,其低粘度在粘度上比水高约1800倍,PSA-PEG纳米颗粒的平均扩散速度仅比纯水中的相同低12倍。相反,由PSA或聚乳酸-乙醇酸共聚物(PLGA)组成的类似尺寸的可生物降解纳米颗粒在CVM中的扩散速度至少比在水中扩散的速度慢3,300倍。 PSA-PEG颗粒还可以迅速渗透囊性纤维化患者肺部排出的痰液,囊性纤维化是一种以高粘弹性粘液分泌为特征的疾病。通过在配制过程中将PEG有效分配到颗粒表面,可以在粘液中快速进行纳米颗粒运输。能够克服人类粘液屏障并提供持续药物释放的可生物降解的聚合物纳米颗粒为改善药物和在粘膜表面的基因传递提供了重要的机会。

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  • 作者单位

    Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218;

    Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218 School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive Northwest, Atlanta, GA 30332.;

    Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218 Institute for NanoBioTechnology, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218;

    Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205;

    Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205;

    Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205;

    Institute for NanoBioTechnology, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218 Division of Pediatric Respiratory Sciences, Johns Hopkins University School of Medicine, 200 North Wolfe Street, Baltimore, MD 21287;

    Johns Hopkins Adult Cystic Fibrosis Program, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, 1830 East Monument Street, Baltimore, MD 21205;

    Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218 Institute for NanoBioTechnology, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218;

    Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218 Institute for NanoBioTechnology, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218 Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205 Department of Oncology and The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    cystic fibrosis; drug delivery; gene therapy; mucosa; mucus-penetrating particle;

    机译:囊性纤维化;药物输送;基因治疗;黏膜粘液穿透颗粒;

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