Nanoparticle diffusion in respiratory mucus from humans without lung disease

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• 作者：Benjamin S. Schuster^a ; ^e ; Jung Soo Suk^a ; ^b ; ^e ; Graeme F. Woodworth^c ; ^d ; ^e ; ¹ ; Justin Hanes^a ; ^b ; ^c ; ^d ; ^e ; ^{hanes@jhu.edu} ; ^{hanes@jhmi.edu}
• 关键词：Inhaled nanoparticles ; Respiratory mucus ; Mucus-penetrating particles ; Multiple particle tracking ; Rheology
• 刊名：Biomaterials
• 出版年：2013
• 出版时间：April, 2013
• 年：2013
• 卷：34
• 期：13
• 页码：3439-3446
• 全文大小：683 K

文摘

A major role of respiratory mucus is to trap inhaled particles, including pathogens and environmental particulates, to limit body exposure. Despite the tremendous health implications, how particle size and surface chemistry affect mobility in respiratory mucus from humans without lung disease is not known. We prepared polymeric nanoparticles densely coated with low molecular weight polyethylene glycol (PEG) to minimize muco-adhesion, and compared their transport to that of uncoated particles in human respiratory mucus, which we collected from the endotracheal tubes of surgical patients with no respiratory comorbidities. We found that 100 and 200?nm diameter PEG-coated particles rapidly penetrated respiratory mucus, at rates exceeding their uncoated counterparts by approximately 15- and 35-fold, respectively. In contrast, PEG-coated particles ¡Ý500?nm in diameter were sterically immobilized by the?mucus mesh. Thus, even though respiratory mucus is a viscoelastic solid at the macroscopic level (as?measured using a bulk rheometer), nanoparticles that are sufficiently small and muco-inert can penetrate the mucus as if it were primarily a viscous liquid. These findings help elucidate the barrier properties of respiratory mucus and provide design criteria for therapeutic nanoparticles capable of penetrating mucus to approach the underlying airway epithelium.