The effect of methylated beta-cyclodextrins on the tight junctions of the rat nasal respiratory epithelium: Electron microscopic and confocal laser scanning microscopic visualization studies

The nasal absorption enhancer randomly methylated beta-cyclodextrin (RAMEB) is thought to increase the paracellular permeability of the nasal epitheli um by opening of the tight junctions. The effects of RAMEB on the cytoskele ton of the rat nasal epithelium in vivo were determined by confocal laser s canning microscopy (CLSM). The effects on the tight junctions of the rat na sal epithelium were also investigated, using transmission electron microsco py (TEM) of thin sections. The effects of RAMEB were compared with those of the absorption enhancer sodium taurodihydrofusidate (STDHF). Fifteen minut es after nasal administration of 2% RAMEB in vivo, the distribution of cyto skeletal actin was comparable to the untreated control, suggesting that RAM EB does not cause opening of the tight junctions via cytoskeletal interacti ons. In contrast, administration of 1% STDHF resulted in changes in the act in staining. Furthermore, with TEM severe damage of the nasal epithelium wa s observed after treatment with 1% STDHF. Ultrastructural changes of the ti ght junctions were not apparent in TEM sections after treatment with 2% RAM EB. In conclusion, CLSM and TEM are suitable methods to visualize the effec ts of absorption enhancers on nasal epithelial morphology. (C) 1999 Elsevie r Science B.V. All rights reserved.