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沙门氏菌样生物粘附纳米颗粒

Salmonella-like bioadhesive nanoparticles.

作者信息

Salman Hesham H, Gamazo Carlos, Campanero Miguel A, Irache Juan M

机构信息

Centro Galénico, Facultad de Farmacia, University of Navarra, Apartado. 177, 31080 Pamplona, Spain.

出版信息

J Control Release. 2005 Aug 18;106(1-2):1-13. doi: 10.1016/j.jconrel.2005.03.033.

Abstract

The aim of this work was to evaluate the bioadhesive potential of a polymeric vector obtained by the association between Gantrez AN nanoparticles and flagella-enriched Salmonella enteritidis extract. Fluorescently labelled nanoparticles (SE-NP) were prepared, after incubation between the polymer and the extract, by a solvent displacement method and cross-linkage with 1,3-diaminopropane. SE-NP displayed a size close to 280 nm and the amount of associated bacterial extract was 18 mug/mg nanoparticle. Flagellin represents more than 80% of the total proteins associated with SE-NP, which was identified by SDS-PAGE and confirmed by Western blotting. Concerning the bioadhesive properties, SE-NP shows an important tropism for the ileum. In fact, about 50% of the given dose of SE-NP was found in this gut region for at least 3 h. Interestingly, the bioadhesive ability of SE-NP correlated well with the described colonisation profile for Salmonella enteritidis. This fact was corroborated by competitive tissue distribution studies. Thus, when SE-NP and Salmonella cells were administered together by the oral route, both the bacteria and the nanoparticles displayed a similar distribution within the intestinal mucosa. However, the ability of SE-NP to be taken up by Peyer's patches appeared to be negatively affected by the presence of the bacteria. Similarly, when SE-NP was administered 30 min before cells, SE-NP were found broadly distributed in Peyer's patches, whereas the bacteria were neither able to adhere to nor penetrate this lymphoid tissue. In summary, SE-NP demonstrated their Salmonella-like gut colonization, which can be a useful vector for oral targeting strategies.

摘要

本研究旨在评估由甘膦树脂AN纳米颗粒与富含鞭毛的肠炎沙门氏菌提取物结合得到的聚合物载体的生物黏附潜力。在聚合物与提取物孵育后,通过溶剂置换法并用1,3 -二氨基丙烷交联制备了荧光标记的纳米颗粒(SE - NP)。SE - NP的尺寸接近280 nm,每毫克纳米颗粒结合的细菌提取物量为18 μg。鞭毛蛋白占与SE - NP结合的总蛋白的80%以上,通过SDS - PAGE鉴定并经蛋白质免疫印迹法确认。关于生物黏附特性,SE - NP对回肠表现出显著的嗜性。事实上,在该肠道区域发现给予剂量的约50%的SE - NP至少存在3小时。有趣的是,SE - NP的生物黏附能力与所描述的肠炎沙门氏菌的定殖情况密切相关。这一事实通过竞争性组织分布研究得到了证实。因此,当通过口服途径同时给予SE - NP和沙门氏菌细胞时,细菌和纳米颗粒在肠黏膜内均呈现相似的分布。然而,细菌的存在似乎对SE - NP被派伊尔氏结摄取的能力产生了负面影响。同样,当在给予细胞前30分钟给予SE - NP时,发现SE - NP广泛分布于派伊尔氏结中,而细菌既无法黏附也无法穿透该淋巴组织。总之,SE - NP展示了其类似沙门氏菌的肠道定殖能力,这对于口服靶向策略可能是一种有用的载体。

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