Hinkley Georgia K, Carpinone Paul, Munson John W, Powers Kevin W, Roberts Stephen M
Center for Environmental and Human Toxicology, University of Florida, Box 110885, Gainesville, FL, 32611, USA.
Major Analytical and Particle Analysis Instrumentation Center, University of Florida, Box 116400, Gainesville, FL, 32611, USA.
Part Fibre Toxicol. 2015 Mar 25;12:9. doi: 10.1186/s12989-015-0085-5.
Particle size is thought to be a critical factor affecting the bioavailability of nanoparticles following oral exposure. Nearly all studies of nanoparticle bioavailability focus on characterization of the primary particle size of the material as supplied or as dosed, and not on agglomeration behavior within the gastrointestinal tract, which is presumably most relevant for absorption.
In the study reported here, snapshots of agglomeration behavior of gold nanospheres were evaluated in vivo throughout the gastrointestinal tract using transmission electron microscopy. Agglomeration state within the gastrointestinal tract was then used to help explain differences in gastrointestinal particle absorption, as indicated by tissue levels of gold detected using inductively coupled plasma mass spectrometry. Mice were dosed (10 mg/kg) with either 23 nm PEG-coated or uncoated gold nanospheres.
Transmission electron microscopy demonstrates that PEG-coated gold nanoparticles can be observed as primary, un-agglomerated particles throughout the gastrointestinal tract and feces of dosed animals. In contrast, uncoated gold nanoparticles were observed to form agglomerates of several hundred nanometers in all tissues and feces. Inductively coupled plasma mass spectrometry shows significantly higher levels of gold in tissues from animals dosed with PEG-coated versus uncoated 23 nm gold nanoparticles. Retention of particles after a single oral gavage was also very high, with all tissues of animals dosed with PEG-coated particles having detectable levels of gold at 30 days following exposure.
Qualitative observation of these particles in vivo shows that dispersed PEG-coated particles are able to reach the absorptive tissues of the intestine while agglomerated uncoated particles are sequestered in the lumen of these tissues. However, the large differences observed for in vivo agglomeration behavior were not reflected in oral absorption, as indicated by gold tissue levels. Additional factors, such as surface chemistry, may have played a more important role than in vivo particle size and should be investigated further.
粒径被认为是影响纳米颗粒经口暴露后生物利用度的关键因素。几乎所有关于纳米颗粒生物利用度的研究都集中在对所提供材料或给药时的初级粒径进行表征，而不是胃肠道内的团聚行为，而胃肠道内的团聚行为可能与吸收最为相关。
在本报告的研究中，使用透射电子显微镜在体内评估了整个胃肠道内金纳米球的团聚行为快照。然后，利用胃肠道内的团聚状态来帮助解释胃肠道颗粒吸收的差异，这通过电感耦合等离子体质谱法检测到的金组织水平来表明。给小鼠（10毫克/千克）灌胃23纳米聚乙二醇包被或未包被的金纳米球。
透射电子显微镜显示，在给药动物的整个胃肠道和粪便中，聚乙二醇包被的金纳米颗粒可观察为初级的、未团聚的颗粒。相比之下，在所有组织和粪便中均观察到未包被的金纳米颗粒形成了数百纳米的聚集体。电感耦合等离子体质谱显示，与未包被的23纳米金纳米颗粒相比，给动物灌胃聚乙二醇包被的金纳米颗粒后，组织中的金水平显著更高。单次灌胃后颗粒的保留率也非常高，在暴露后30天，给聚乙二醇包被颗粒的动物的所有组织中均有可检测到的金水平。
对这些颗粒的体内定性观察表明，分散的聚乙二醇包被颗粒能够到达肠道的吸收组织，而团聚的未包被颗粒则被隔离在这些组织的管腔中。然而，体内团聚行为观察到的巨大差异并未反映在口服吸收中，如金组织水平所示。其他因素，如表面化学，可能比体内粒径发挥了更重要的作用，应进一步研究。
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