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利用人乳的潜力提高纳米颗粒和大分子的肠道通透性

Harnessing the Potential of Human Breast Milk to Boost Intestinal Permeability for Nanoparticles and Macromolecules.

作者信息

Naftaly Si, Pery Topaz, Mhajne Rawan, Ashkar Areen, Davidovich-Pinhas Maya, Zinger Assaf

机构信息

Laboratory for Bioinspired Nano Engineering and Translational Therapeutics, Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel.

Faculty of Biotechnology and Food Engineering, Technion, Israel.

出版信息

J Control Release. 2025 Mar 10;379:768-785. doi: 10.1016/j.jconrel.2025.01.049. Epub 2025 Jan 25.

Abstract

The intricate interplay between human breast milk, nanoparticles, and macromolecules holds promise for innovative nutritional delivery strategies. Compared to bovine milk and infant formula, this study explores human breast milk's role in modulating intestinal permeability and its impact on nanoparticle and macromolecule transport. Comparative analysis with bovine milk and infant formula reveals significant elevations in permeability with human breast milk, accompanied by a decrease in transepithelial electrical resistance, suggesting enhanced paracellular transport. Mechanistically, human breast milk reduces Zonula occludens-1 levels, suggesting a regulatory role in intestinal barrier function. Through in vitro and ex vivo evaluations, we aim to understand better the mechanisms behind enhanced permeability and how human breast milk affects nanoparticle physicochemical properties, potentially modulating their behavior. Specifically, human breast milk improves the intestinal permeability of liposomes in a porcine intestinal model, with associated changes in the composition of milk proteins corona related to liposome charge. These findings underscore the unexploited potential of human breast milk in facilitating transport across the intestinal barrier, offering novel avenues for human nutritional delivery and therapeutic interventions.

摘要

人乳、纳米颗粒和大分子之间复杂的相互作用为创新的营养递送策略带来了希望。与牛乳和婴儿配方奶粉相比,本研究探讨了人乳在调节肠道通透性及其对纳米颗粒和大分子转运的影响方面的作用。与牛乳和婴儿配方奶粉的比较分析表明,人乳会使通透性显著升高,同时跨上皮电阻降低,这表明细胞旁转运增强。从机制上讲,人乳会降低闭合蛋白-1的水平,这表明其在肠道屏障功能中具有调节作用。通过体外和离体评估,我们旨在更好地了解通透性增强背后的机制,以及人乳如何影响纳米颗粒的物理化学性质,从而可能调节它们的行为。具体而言,人乳可提高猪肠道模型中脂质体的肠道通透性,同时与脂质体电荷相关的乳蛋白冠层组成也会发生变化。这些发现强调了人乳在促进跨肠道屏障转运方面尚未被开发的潜力,为人的营养递送和治疗干预提供了新途径。

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