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
E. Marttin et al., 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, J CONTR REL, 57(2), 1999, pp. 205-213
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.