The penetration of fresh undiluted sputum expectorated by cystic fibrosis patients by non-adhesive polymer nanoparticles

被引:270
|
作者
Suk, Jung Soo [2 ]
Lai, Samuel K. [1 ]
Wang, Ying-Ying [2 ]
Ensign, Laura M. [1 ]
Zeitlin, Pamela L. [3 ,4 ]
Boyle, Michael P. [5 ]
Hanes, Justin [1 ,2 ,3 ]
机构
[1] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA
[2] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Inst NanoBioTechnol, Baltimore, MD 21218 USA
[4] Johns Hopkins Univ, Sch Med, Div Pediat Resp Sci, Baltimore, MD 21287 USA
[5] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Johns Hopkins Adult Cyst Fibrosis Program, Baltimore, MD 21205 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
Lung disease; Nanoparticle therapeutics; Mucus; Mucus penetrating particles; Particle tracking; Rheology; MULTIPLE-PARTICLE TRACKING; GENE-THERAPY; LUNG-DISEASE; HUMAN MUCUS; TRANSPORT; DIFFUSION; DELIVERY; DRUG; VECTORS; BARRIER;
D O I
10.1016/j.biomaterials.2008.12.076
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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 mn 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 similar to 140 +/- 50 nm (range; 60-300 nm). Taken together, these results demonstrate that nanoparticles up to 200 mn 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. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2591 / 2597
页数:7
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