A Novel Drug Delivery System for the Human Nasal Epithelium.
A Novel Drug Delivery System for the Human Nasal Epithelium.
复制标题
用于人鼻上皮的新型药物输送系统。
DOI：
10.1159/000441877
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Himi T.
中科院分区：
文献类型：
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作者：
Takano K;Kojima T;Keira T;Miyata R;Nomura K;Kakuki T;Kaneko Y;Yajima R;Kakiuchi A;Himi T.
上呼吸道组织如人鼻粘膜的上皮通过紧密连接（TJ）形成连续屏障。目前正在重新考虑开发用于鼻粘膜的药物递送系统。在通过鼻粘膜的鼻内给药中，由TJ调节的细胞旁途径极其重要。已知产气荚膜梭菌肠毒素（C-CPE）的C-末端片段结合TJ蛋白claudin并破坏紧密连接屏障而不诱导细胞毒性效应。我们研究了C-CPE突变体对人鼻上皮细胞（HNECs）TJ功能的影响以及对人重组胰岛素在C-CPE 194和C-CPE m19处理的HNECs中渗透性的影响。我们最近报道了C-CPE突变体m194和m19可以通过MAPK途径调节胰岛素穿过HNECs的渗透性，并且可能通过直接鼻内胰岛素给药在治疗各种疾病中发挥关键作用。另一方面，已知microRNA（miRNAs）作为基因中的直接或间接靶标调节TJ的表达以维持屏障功能。我们研究了miRNA对HNECs上皮屏障的影响，发现miRNA-146 a在维持TJ屏障和对抗入侵病原体的先天免疫应答中起着至关重要的作用。本章从上皮屏障功能的角度综述了一种新的跨鼻粘膜给药系统。© 2016 S. Karger AG，Basel鼻内胰岛素给药具有治疗阿尔茨海默病的潜力，因为药物直接分布到大脑，而不会进入全身血液循环[1]。人鼻上皮细胞是抵抗吸入物质和病原体的第一道物理屏障，部分受紧密连接（TJ）调节[2，3]。目前，许多研究小组正在开发穿过鼻粘膜的药物递送系统。由TJ调节的细胞旁途径在细胞内的免疫调节中起着极其重要的作用。
The epithelium of upper respiratory tissues such as the human nasal mucosa forms a continuous barrier via tight junctions (TJs). The development of a drug delivery system for use across the nasal mucosa is being reconsid-ered. In intranasal administration across the nasal mu-cosa, the paracellular pathway regulated by TJs is extremely important. It is known that the C-terminal frag-ment of Clostridium perfringens enterotoxin (C-CPE) binds the TJ protein claudin and disrupts the tight junctional barrier without inducing a cytotoxic effect. We investigated the effects of C-CPE mutants on the function of TJs of human nasal epithelial cells (HNECs) and on the permeability of human recombinant insulin across HNECs treat-ed with C-CPE 194 and C-CPE m19. We recently reported that C-CPE mutants 194 and m19 can regulate the perme-ability of insulin across HNECs via the MAPK pathway and may play a crucial role in therapy for various diseases via direct intranasal insulin administration. On the other hand, microRNAs (miRNAs) are known to regulate the expression of TJs as direct or indirect targets in genes to maintain barrier function. We investigated the effects of miRNAs on the epithelial barrier of HNECs and found that miRNA-146a plays crucial roles in the maintenance of the TJ barrier and innate immune response against invading pathogens. This chapter reviews a novel drug delivery system across the nasal mucosa from the point of view of the epithelial barrier function.© 2016 S. Karger AG, BaselIntranasal insulin administration has therapeutic potential for Alzheimer's disease because of the direct distribution of the agent to the brain without movement into the systemic blood circulation [1]. The human nasal epithelium acts as the first physical barrier against inhaled substances and pathogens, which is partially regulated by tight junctions (TJs)[2, 3]. Many groups are currently developing drug delivery systems to traverse the nasal mucosa. The paracellular pathway regulated by TJs plays an extremely important role in intra-