鼻腔给药人体吸收的细胞模型方法学研究进展

Advance of Cell Model Methodology for Human Absorption Evaluation of Nasal Administration

关键词:  经鼻给药  鼻腔上皮  体外细胞模型  药物研发

Key words:  intranasal administration  nasal epithelium  in vitro cell model  drug developments

摘要:

经鼻给药具备起效快，生物利用度高，入脑效率高及非侵入性等优点。但复杂的鼻腔微环境，如黏膜屏障、纤毛运动、低pH值的黏液层及酶降解等因素，为鼻腔药物研发带来了诸多挑战。尽管大量动物试验方法已经为鼻腔药物的研发提供了研究手段，但物种间的差异、高额的费用及较长的周期等因素限制了这些方法在研发中的应用，特别是在新药临床前的化合物及处方早期筛选阶段。因此，选择一种具备良好体内外相关性的鼻腔细胞模型用于指导药物的临床前研发成为了关键。基于鼻腔给药途径，无论经鼻入脑或是经鼻入血，上皮细胞的屏障作用均直接决定药物的生物利用度与药效。此外，鼻腔药物黏膜刺激性等毒理评价也是研发成功的关键因素。因此，本文归纳了现阶段基于鼻腔上皮细胞构建的体外鼻腔模型在鼻用制剂研发中的应用现状。

Abstract:

Intranasal administration has the advantages of quick onset, high bioavailability, potential delivery into brain, and non-invasive. However, the limitations of the complex nasal microenvironment, such as the mucosal barrier, ciliary movement, low pH mucous layer, and enzyme degradation, appear to be key challenges in nasal drug development. Although a large number of animal trials provide reference data for the development of nasal drugs, the species differences, high cost and long cycle make this approach more difficult to develop, especially in the high-throughput preclinical screening stage of new drugs. Therefore, it is critical to select a nasal model with good in vitro and in vivo correlation for preclinical drug research. Whether the targeting through the nasal into the brain or blood, the epithelial cell barrier directly determines the bioavailability and efficacy during the intranasal administration. Moreover, mucosal irritation is also one of the critical evaluations of the safety aspects during nasal drugs development, where cell model can be quite useful. Therefore, this review summarized the application of the in vitro nasal model based on nasal epithelial cells in the nasal drug development.