Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
PLoS One. 2011;6(6):e21547. doi: 10.1371/journal.pone.0021547. Epub 2011 Jun 29.
Mucus secretions typically protect exposed surfaces of the eyes and respiratory, gastrointestinal and female reproductive tracts from foreign entities, including pathogens and environmental ultrafine particles. We hypothesized that excess exposure to some foreign particles, however, may cause disruption of the mucus barrier. Many synthetic nanoparticles are likely to be mucoadhesive due to hydrophobic, electrostatic or hydrogen bonding interactions. We therefore sought to determine whether mucoadhesive particles (MAP) could alter the mucus microstructure, thereby allowing other foreign particles to more easily penetrate mucus. We engineered muco-inert probe particles 1 µm in diameter, whose diffusion in mucus is limited only by steric obstruction from the mucus mesh, and used them to measure possible MAP-induced changes to the microstructure of fresh human cervicovaginal mucus. We found that a 0.24% w/v concentration of 200 nm MAP in mucus induced a ∼10-fold increase in the average effective diffusivity of the probe particles, and a 2- to 3-fold increase in the fraction capable of penetrating physiologically thick mucus layers. The same concentration of muco-inert particles, and a low concentration (0.0006% w/v) of MAP, had no detectable effect on probe particle penetration rates. Using an obstruction-scaling model, we determined that the higher MAP dose increased the average mesh spacing ("pore" size) of mucus from 380 nm to 470 nm. The bulk viscoelasticity of mucus was unaffected by MAP exposure, suggesting MAP may not directly impair mucus clearance or its function as a lubricant, both of which depend critically on the bulk rheological properties of mucus. Our findings suggest mucoadhesive nanoparticles can substantially alter the microstructure of mucus, highlighting the potential of mucoadhesive environmental or engineered nanoparticles to disrupt mucus barriers and cause greater exposure to foreign particles, including pathogens and other potentially toxic nanomaterials.
黏液分泌物通常可保护眼睛、呼吸道、胃肠道和女性生殖道等暴露表面免受外来物，包括病原体和环境超细颗粒的侵害。我们假设，然而，过多地暴露于某些外来颗粒可能会破坏黏液屏障。许多合成纳米颗粒由于疏水、静电或氢键相互作用而很可能具有黏液附着性。因此，我们试图确定黏液附着性颗粒（MAP）是否会改变黏液的微观结构，从而使其他外来颗粒更容易穿透黏液。我们设计了直径为 1 µm 的黏液惰性探针颗粒，其在黏液中的扩散仅受到来自黏液网格的空间位阻的限制，并使用它们来测量 MAP 对新鲜人宫颈黏液的微观结构可能产生的变化。我们发现，浓度为 0.24%（w/v）的 200nm MAP 可使探针颗粒的平均有效扩散系数增加约 10 倍，并使能够穿透生理厚度黏液层的部分增加 2 至 3 倍。相同浓度的黏液惰性颗粒和低浓度（0.0006%（w/v））的 MAP 对探针颗粒的穿透率没有可检测到的影响。使用阻塞缩放模型，我们确定更高剂量的 MAP 增加了黏液的平均网格间距（“孔”大小），从 380nm 增加到 470nm。MAP 暴露对黏液的整体粘弹性没有影响，这表明 MAP 可能不会直接损害黏液清除功能或其作为润滑剂的功能，这两者都严重依赖于黏液的整体流变学特性。我们的研究结果表明，黏液附着性纳米颗粒可以显著改变黏液的微观结构，突出了黏液附着性环境或工程纳米颗粒破坏黏液屏障并导致更多外来颗粒，包括病原体和其他潜在有毒纳米材料暴露的潜在可能性。
