Ex Vivo Characterization of Particle Transport in Mucus Secretions Coating Freshly Excised Mucosal Tissues

被引:88
作者
Ensign, Laura M. [1 ,2 ]
Henning, Andreas [1 ,2 ]
Schneider, Craig S. [1 ,2 ]
Maisel, Katharina [1 ,3 ]
Wang, Ying-Ying [1 ,3 ,4 ]
Porosoff, Marc D. [1 ,2 ]
Cone, Richard [1 ,4 ]
Hanes, Justin [1 ,2 ,3 ,5 ,6 ,7 ,8 ]
机构
[1] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Ctr Nanomed, Baltimore, MD 21231 USA
[2] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA
[3] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Dept Biophys, Baltimore, MD 21218 USA
[5] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21287 USA
[6] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA
[7] Johns Hopkins Univ, Inst NanoBioTechnol, Ctr Canc Nanotechnol Excellence, Baltimore, MD 21218 USA
[8] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD 21231 USA
基金
美国国家科学基金会;
关键词
mucus penetrating particles; particle tracking; drug delivery; POLYMERIC NANOPARTICLES; GASTROINTESTINAL MUCUS; BARRIER PROPERTIES; DELIVERY-SYSTEMS; HIV SURROGATES; DRUG-DELIVERY; CELL-FREE; PENETRATION; DIFFUSION; REVEAL;
D O I
10.1021/mp400087y
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
100103 [病原生物学]; 100218 [急诊医学];
摘要
Sustained drug delivery to mucosal surfaces has the potential to improve the effectiveness of prophylactic and therapeutic treatments for numerous diseases and conditions, including inflammatory bowel disease, sexually transmitted diseases, cystic fibrosis, glaucoma, dry eye, and various cancers. Sustained delivery systems such as nanoparticles can be useful for mucosal delivery, but recent work suggests they must penetrate the rapidly cleared mucus barrier that overlies all mucosal epithelia to achieve uniform distribution on epithelial surfaces and enhanced residence time. Thus, it is important to evaluate the mucus-penetrating ability of nanosized delivery systems in preclinical animal studies, and for administration to humans. We describe a simple ex vivo method to visualize and quantify nanoparticle transport in mucus on fresh mucosal tissues. Using this method in murine models, we observed variations in the mucus mesh at different anatomical locations, as well as cyclical variations that may have implications for mucosal delivery.
引用
收藏
页码:2176 / 2182
页数:7
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