Nanoparticle Digestion Simulator Reveals pH-dependent Aggregation in the Gastrointestinal Tract.
Nanoparticle Digestion Simulator Reveals pH-dependent Aggregation in the Gastrointestinal Tract.
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DOI：
10.1021/acs.analchem.0c01844
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发表时间：
2020-08
影响因子：
7.4
通讯作者：
Jia H Shi;J. Axson;I. Bergin;A. Ault
中科院分区：
文献类型：
--
作者：
Jia H Shi;J. Axson;I. Bergin;A. Ault
确定胃肠道内摄入的纳米颗粒的物理化学性质对于评估环境暴露的影响和纳米颗粒药物传递的潜力至关重要。然而，由于胃肠道内化学环境的变化，预测纳米颗粒在肠道吸收点的物理化学性质具有挑战性。本文构建了一个动态纳米颗粒消化模拟器（NDS）来检测纳米颗粒在胃和上肠中pH和盐浓度变化时的演变。这个多室，流动通过系统模拟消化通过转移胃肠道液体和消化分泌物在生理相关的时间尺度和流速。研究发现，初始流体动力学直径（Dh）为24.6±0.4 nm的银纳米颗粒（柠檬酸盐包覆）在空腹（pH 2）和空腹（pH 5）胃条件下，通过纳米颗粒跟踪分析（NTA）观察其粒径分布，并通过透射电子显微镜（TEM-EDX）观察其形貌和元素组成。在空腹条件下，颗粒聚集到Dh = 130±10 nm，并在上肠室（十二指肠和空肠）保持大聚集，以Dh = 110±20 nm结束，较小的模式为59±8 nm。相比之下，在喂食条件下，纳米颗粒在胃中聚集到60±10 nm，然后在肠室中分解成单个纳米颗粒（26±2 nm）。NDS为研究纳米颗粒在胃肠道内的物理化学修饰以及有意和无意摄入纳米颗粒的影响提供了一种分析方法。
Determining the physicochemical properties of ingested nanoparticles within the gastrointesti-nal tract is critical for evaluating the impact of environmental exposure and potential for nano-particle drug delivery. However, it is challenging to predict nanoparticle physicochemical prop-erties at the point of intestinal absorption due to the changing chemical environments within the gastrointestinal tract. Herein, a dynamic nanoparticle digestion simulator (NDS) was con-structed to examine nanoparticle evolution due to changing pH and salt concentrations in the stomach and upper intestine. This multi-compartment, flow-through system simulates digestion by transferring gastrointestinal fluids and digestive secretions at physiologically-relevant time scales and flow rates. Pronounced differences in aggregation and aggregate stability were ob-served with silver nanoparticles (citrate-coated) with an initial hydrodynamic diameter (Dh) of 24.6 ± 0.4 nm examined under fasted (pH 2) and fed (pH 5) gastric conditions using nanoparti-cle tracking analysis (NTA) for size distributions and transmission electron microscopy with energy dispersive x-ray spectroscopy (TEM-EDX) for morphology and elemental composition. Under fasted stomach conditions particles aggregated to Dh = 130 ± 10 nm and remained as large aggregates in the upper intestinal compartments (duodenum and jejunum) ending with Dh = 110 ± 20 nm and a smaller mode at 59 ± 8 nm. In contrast, under fed conditions nanoparticles aggregated to 60 ± 10 nm in the stomach, then disaggregated to individual nanoparticles (26 ± 2 nm) in the intestinal compartments. The NDS provides an analytical approach for studying na-noparticle physicochemical modifications within the gastrointestinal tract and the impacts of intentionally and unintentionally ingested nanoparticles.