RPMI 2650 epithelial model and three-dimensional reconstructed human nasal mucosa as in vitro models for nasal permeation studies.

摘要

The purpose of this study was to investigate the human nasal epithelial cell line RPMI 2650 regarding its usefulness as in vitro model for drug permeation studies. Particularly, the influence of the air-liquid interface in culture and coculture with human nasal fibroblasts (HNF) on the differentiation and permeation barrier properties of the cell layer was examined. In addition to a non-contact coculture, we developed a three-dimensional construct of the human nasal mucosa composed of a collagen matrix with embedded HNF, covered by a RPMI 2650 epithelial cell layer. Microscopic examination as well as measurement of the transepithelial electrical resistance and permeation experiments showed the importance of cultivation at the air-liquid interface. Permeation studies were performed using a paracellular marker (sodium fluorescein), a transcellular marker (propranolol-HCl) and a model substance with high molecular weight (FITC-dextran, MW 4000). The epithelial model showed an organotypic permeation barrier for paracellular, transcellular and high MW permeation. Three-dimensional reconstructed human nasal mucosa showed four- to fivefold higher permeation coefficients. Regardless of the limits of these models, both offer promise to evaluate passive drug permeation through the nasal mucosa.