The penetration of fresh undiluted sputum expectorated by cystic fibrosis patients by non-adhesive polymer nanoparticles.
The penetration of fresh undiluted sputum expectorated by cystic fibrosis patients by non-adhesive polymer nanoparticles.
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DOI：
10.1016/j.biomaterials.2008.12.076
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发表时间：
2009-05
期刊：
影响因子：
14
通讯作者：
Hanes, Justin
中科院分区：
文献类型：
--
作者：
Suk, Jung Soo;Lai, Samuel K.;Wang, Ying-Ying;Ensign, Laura M.;Zeitlin, Pamela L.;Boyle, Michael P.;Hanes, Justin
高粘弹性和黏附性痰妨碍了囊性纤维化（CF）患者肺中基于纳米颗粒的药物和基因的有效递送。我们试图确定涂有非黏附性聚合物的纳米颗粒是否可以穿透CF痰液，并使用这些“黏附性颗粒”（mip）作为非破坏性纳米探针来表征痰液的微观结构。直径达200纳米的颗粒被低分子量聚乙二醇（PEG）密集包裹，通过未稀释的CF痰液，其平均速度比同等大小的未包裹颗粒快90倍。另一方面，包覆和未包覆的500 nm颗粒的输运受到强烈阻碍。最快的10%的200nm MIPs遇到的痰液的局部粘度仅比水高5倍，而在低剪切速率下，体粘度比水高10,000倍。通过测量不同大小的mip的传输速率并结合阻塞缩放模型，我们确定CF痰液的平均3D网格间距为~140±50 nm（范围：60-300 nm）。综上所述，这些结果表明，直径达200nm的纳米颗粒不粘附在CF痰液上，可以通过进入充满低粘度流体的孔隙，快速穿过这一关键屏障。这一结果也为开发用于CF的药物和基因载体纳米颗粒提供了希望。
Highly viscoelastic and adhesive sputum has precluded efficient nanoparticle-based drug and gene delivery to the lungs of patients with cystic fibrosis (CF). We sought to determine whether nanoparticles coated with non-mucoadhesive polymers could penetrate CF sputum, and to use these “muco-inert particles” (MIPs) as non-destructive nanoprobes to characterize the sputum microstructure. Particles as large as 200 nm in diameter that were densely coated with low MW polyethylene glycol (PEG) moved through undiluted CF sputum with average speeds up to 90-fold faster than similarly-sized uncoated particles. On the other hand, the transport of both coated and uncoated 500 nm particles was strongly hindered. The local viscosity of sputum, encountered by the fastest 10% of 200 nm MIPs, was only 5-fold higher than that of water, whereas the bulk viscosity was 10,000-fold higher at low shear rates. Using measured transport rates of various sized MIPs combined with an obstruction-scaling model, we determined that the average 3D mesh spacing of CF sputum is ~140 ± 50 nm (range: 60-300 nm). Taken together, these results demonstrate that nanoparticles up to 200 nm in diameter that do not adhere to CF sputum can move rapidly through this critical barrier by accessing pores that are filled with a low viscosity fluid. The results also offer hope that desperately needed sputum-penetrating drug- and gene-carrier nanoparticles can be developed for CF.
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影响因子：
16.1
作者：
Lai, Samuel K.;Wang, Ying-Ying;Hanes, Justin
通讯作者：
Hanes, Justin
影响因子：
10.8
作者：
Bures, P;Huang, YB;Peppas, NA
通讯作者：
Peppas, NA
影响因子：
10.8
作者：
Lele, BS;Hoffman, AS
通讯作者：
Hoffman, AS
影响因子：
4.4
作者：
Matsui, H;Verghese, MW;Boucher, RC
通讯作者：
Boucher, RC
DOI：
10.1016/j.ddmec.2007.09.001
发表时间：
2007-01-01
期刊：
Drug discovery today. Disease mechanisms
影响因子：
--
作者：
Clunes, Mark T;Boucher, Richard C
通讯作者：
Boucher, Richard C