Fischell Department of Bioengineering, 2330 Jeong H. Kim Engineering Building, University of Maryland, College Park, MD 20742, USA.
J Control Release. 2012 Oct 10;163(1):25-33. doi: 10.1016/j.jconrel.2012.06.007. Epub 2012 Jun 12.
Bioavailability of oral drugs, particularly large hydrophilic agents, is often limited by poor adhesion and transport across gastrointestinal (GI) epithelial cells. Drug delivery systems, such as sub-micrometer polymer carriers (nanocarriers, NCs) coupled to affinity moieties that target GI surface markers involved in transport, may improve this aspect. To explore this strategy, we coated 100-nm polymer particles with an antibody to ICAM-1 (a protein expressed on the GI epithelium and other tissues) and evaluated targeting, uptake, and transport in human GI epithelial cells. Fluorescence and electron microscopy, and radioisotope tracing revealed that anti-ICAM NCs specifically bound to cells in culture, were internalized via CAM-mediated endocytosis, trafficked by transcytosis across cell monolayers without disrupting the permeability barrier or cell viability, and enabled transepithelial transport of a model therapeutic enzyme (α-galactosidase, deficient in lysosomal Fabry disease). These results indicate that ICAM-1 targeting may provide delivery of therapeutics, such as enzymes, to and across the GI epithelium.
口服药物（尤其是大亲水性药物）的生物利用度往往受到跨胃肠道（GI）上皮细胞的粘附和转运能力差的限制。药物传递系统，如与靶向参与转运的 GI 表面标志物的亲和部分偶联的亚微米聚合物载体（纳米载体，NCs），可能会改善这一方面。为了探索这一策略，我们用针对细胞间黏附分子-1（GI 上皮和其他组织表达的一种蛋白）的抗体对 100nm 聚合物颗粒进行了涂层，并在人胃肠道上皮细胞中评估了靶向性、摄取和转运。荧光和电子显微镜以及放射性同位素示踪显示，抗 ICAM-NC 特异性地与培养中的细胞结合，通过 CAM 介导的内吞作用被内化，通过跨细胞单层的转胞吞作用运输，而不会破坏通透性屏障或细胞活力，并能够使模型治疗酶（缺乏溶酶体法布里病的α-半乳糖苷酶）进行跨上皮转运。这些结果表明，ICAM-1 靶向可能为治疗药物（如酶）的输送提供了途径，使其能够到达并穿过胃肠道上皮细胞。
