Maisel Katharina, Ensign Laura, Reddy Mihika, Cone Richard, Hanes Justin
Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, United States; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, United States.
Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, United States; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD 21231, United States.
J Control Release. 2015 Jan 10;197:48-57. doi: 10.1016/j.jconrel.2014.10.026. Epub 2014 Nov 4.
It is believed that mucoadhesive surface properties on particles delivered to the gastrointestinal (GI) tract improve oral absorption or local targeting of various difficult-to-deliver drug classes. To test the effect of nanoparticle mucoadhesion on distribution of nanoparticles in the GI tract, we orally and rectally administered nano- and microparticles that we confirmed possessed surfaces that were either strongly mucoadhesive or non-mucoadhesive. We found that mucoadhesive particles (MAP) aggregated in mucus in the center of the GI lumen, far away from the absorptive epithelium, both in healthy mice and in a mouse model of ulcerative colitis (UC). In striking contrast, water absorption by the GI tract rapidly and uniformly transported non-mucoadhesive mucus-penetrating particles (MPP) to epithelial surfaces, including reaching the surfaces between villi in the small intestine. When using high gavage fluid volumes or injection into ligated intestinal loops, common methods for assessing oral drug and nanoparticle absorption, we found that both MAP and MPP became well-distributed throughout the intestine, indicating that the barrier properties of GI mucus were compromised. In the mouse colorectum, MPP penetrated into mucus in the deeply in-folded surfaces to evenly coat the entire epithelial surface. Moreover, in a mouse model of UC, MPP were transported preferentially into the disrupted, ulcerated tissue. Our results suggest that delivering drugs in non-mucoadhesive MPP is likely to provide enhanced particle distribution, and thus drug delivery, in the GI tract, including to ulcerated tissues.
人们认为，递送至胃肠道（GI）的颗粒的粘膜粘附表面特性可改善各种难递送药物类别的口服吸收或局部靶向性。为了测试纳米颗粒粘膜粘附对纳米颗粒在胃肠道中分布的影响，我们经口和直肠给药了纳米颗粒和微米颗粒，我们确认这些颗粒的表面具有强粘膜粘附性或非粘膜粘附性。我们发现，在健康小鼠和溃疡性结肠炎（UC）小鼠模型中，粘膜粘附颗粒（MAP）都聚集在胃肠道管腔中心的粘液中，远离吸收性上皮。与之形成鲜明对比的是，胃肠道的水分吸收迅速且均匀地将非粘膜粘附性粘液穿透颗粒（MPP）转运至上皮表面，包括到达小肠绒毛之间的表面。当使用高灌胃液体体积或注射到结扎肠袢中的常见方法来评估口服药物和纳米颗粒的吸收时，我们发现MAP和MPP在整个肠道中分布良好，这表明胃肠道粘液的屏障特性受到了损害。在小鼠结肠直肠中，MPP深入渗透到褶皱表面的粘液中，均匀地覆盖整个上皮表面。此外，在UC小鼠模型中，MPP优先转运至受损的溃疡组织。我们的结果表明，以非粘膜粘附性MPP递送药物可能会增强颗粒在胃肠道中的分布，从而增强药物递送，包括递送至溃疡组织。
