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 epithelium by opening of the tight junctions. The effects of RAMEB on the cytoskeleton of the rat nasal epithelium in vivo were determined by confocal laser scanning microscopy (CLSM). The effects on the tight junctions of the rat nasal epithelium were also investigated, using transmission electron microscopy (TEM) of thin sections. The effects of RAMEB were compared with those of the absorption enhancer sodium taurodihydrofusidate (STDHF). Fifteen minutes after nasal administration of 2% RAMEB in vivo, the distribution of cytoskeletal actin was comparable to the untreated control, suggesting that RAMEB does not cause opening of the tight junctions via cytoskeletal interactions. In contrast, administration of 1% STDHF resulted in changes in the actin staining. Furthermore, with TEM severe damage of the nasal epithelium was observed after treatment with 1% STDHF. Ultrastructural changes of the tight junctions were not apparent in TEM sections after treatment with 2% RAMEB. In conclusion, CLSM and TEM are suitable methods to visualize the effects of absorption enhancers on nasal epithelial morphology.
Marttin
E
E
Leiden/Amsterdam Center for Drug Research, Division of Pharmaceutical Technology and Biopharmaceutics, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Verhoef
J C
JC
Spies
F
F
van der Meulen
J
J
Nagelkerke
J F
JF
Koerten
H K
HK
Merkus
F W
FW
D000199:Actins / Q000737:chemistry; D000281:Administration, Intranasal; D000818:Animals; D003505:Cyclodextrins / Q000494:pharmacology*; D004848:Epithelium / Q000648:ultrastructure; D008297:Male; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009297:Nasal Mucosa / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D019108:Tight Junctions / Q000187:drug effects*; D047392:beta-Cyclodextrins