Claudin 4-targeted protein incorporated into PLGA nanoparticles can mediate M cell targeted delivery.
Claudin 4-targeted protein incorporated into PLGA nanoparticles can mediate M cell targeted delivery.
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DOI：
10.1016/j.jconrel.2009.10.033
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发表时间：
2010-03-03
影响因子：
10.8
通讯作者：
Lo, David D.
中科院分区：
文献类型：
--
作者：
Rajapaksa, Thejani E.;Stover-Hamer, Mary;Fernandez, Xiomara;Eckelhoefer, Holly A.;Lo, David D.
基于聚合物的微粒在临床上的应用主要是因为它们能够控制肽和化合物的释放，但它们也正在探索其将疫苗和药物以悬浮液形式直接输送到粘膜部位的潜力。一般认为摄取是由上皮 M 细胞介导的，但这通常无法直接测量。为了研究体内优化 M 细胞摄取聚合物微粒的潜力，我们生产了掺有重组蛋白的亚微米尺寸 PLGA 颗粒。这种重组蛋白是在含有或不含有 C 端肽的情况下产生的，先前显示该肽与 Claudin 4（一种与 M 细胞内吞作用相关的蛋白质）具有高亲和力结合。虽然 PLGA 纳米粒子将蛋白质整合到整个基质中，但大部分蛋白质也展示在表面上，使我们能够利用靶向肽的结合活性。因此，我们发现将这些纳米颗粒滴注到小鼠的鼻道或胃中可以显着增强上呼吸道和肠道 M 细胞对它们的摄取。我们的结果表明，相当简单的纳米颗粒制造方法可以为开发有效的无针输送系统提供见解。
Polymer-based microparticles are in clinical use mainly for their ability to provide controlled release of peptides and compounds, but they are also being explored for their potential to deliver vaccines and drugs as suspensions directly into mucosal sites. It is generally assumed that uptake is mediated by epithelial M cells, but this is often not directly measured. To study the potential for optimizing M cell uptake of polymer microparticles in vivo, we produced sub-micron size PLGA particles incorporating a recombinant protein. This recombinant protein was produced with or without a c-terminal peptide previously shown to have high affinity binding to Claudin 4, a protein associated with M cell endocytosis. While the PLGA nanoparticles incorporate the protein throughout the matrix, much of the protein was also displayed on the surface, allowing us to take advantage of the binding activity of the targeting peptide. Accordingly, we found that instillation of these nanoparticles into the nasal passages or stomach of mice was found to significantly enhance their uptake by upper airway and intestinal M cells. Our results suggest that a reasonably simple nanoparticle manufacture method can provide insight into developing an effective needle-free delivery system.
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DOI：
10.1084/jem.20070607
发表时间：
2007-11-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Nochi T;Yuki Y;Matsumura A;Mejima M;Terahara K;Kim DY;Fukuyama S;Iwatsuki-Horimoto K;Kawaoka Y;Kohda T;Kozaki S;Igarashi O;Kiyono H
通讯作者：
Kiyono H
影响因子：
3.9
作者：
Crotts, G;Park, TG
通讯作者：
Park, TG
影响因子：
10.8
作者：
Igartua, M;Hernández, RM;Pedraz, JL
通讯作者：
Pedraz, JL
影响因子：
5.5
作者：
Foster, N;Clark, MA;Hirst, BH
通讯作者：
Hirst, BH
影响因子：
4.8
作者：
Katahira, J;Sugiyama, H;Sugimoto, N
通讯作者：
Sugimoto, N