Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Mol Pharm. 2013 Jun 3;10(6):2176-82. doi: 10.1021/mp400087y. Epub 2013 May 23.
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.
持续向黏膜表面输送药物有可能提高众多疾病和病症的预防和治疗效果，包括炎症性肠病、性传播疾病、囊性纤维化、青光眼、干眼症以及各种癌症。纳米颗粒等持续输送系统可用于黏膜输送，但最近的研究表明，这些系统必须穿透覆盖所有黏膜上皮的快速清除黏液屏障，才能在黏膜上皮表面实现均匀分布并延长停留时间。因此，在临床前动物研究和人类给药中，评估纳米级输送系统的穿透黏液能力非常重要。我们描述了一种简单的离体方法，可用于可视化和量化新鲜黏膜组织上的纳米颗粒在黏液中的输送。在鼠模型中使用该方法，我们观察到不同解剖位置的黏液网格存在差异，以及可能对黏膜输送有影响的周期性变化。
