The effects of water-soluble cyclodextrins on the histological integrity of the rat nasal mucosa.
The aim of this study was to investigate the effect of highly water-soluble cyclodextrins (CDs) on the histological integrity of the nasal mucosa. In order to evaluate their effects, the in vivo single and repeated nasal exposure studies were performed using male Wistar rats. The rat nasal cavity was excised after an application of various CD solutions at different times. The morphological appearances of the rat nasal mucosae were analyzed with the light microscopic and the scanning electron microscopic studies. By utilizing 5-min exposure of each CD solution to the nasal mucosa, no tissue damage was visible for 1.5% w/v beta-CD and 5 and 20% w/v hydroxypropyl beta-CD (HP beta-CD), and the effects were quite similar to controls. However, using 20% w/v randomly methylated beta-CD (RM beta-CD) showed severe damage on the integrity of nasal mucosa. The severity was similar to 1% w/v polyoxyethylene-9-lauryl ether or l% w/v sodium deoxycholate. Meanwhile, 30 or 60 min exposure to 10% w/v HP beta-CD or RM beta-CD resulted in no obvious mucosal damage. In addition, in vivo repeated dosing of RM beta-CD did not show any toxicity up to 20% w/v. These results suggest that at least, less than 10% w/v CD solutions do not induce gross tissue damage and can keep the histological integrity of the nasal mucosa.
Asai
Kazunori
K
Department or Pharmacy, Matsudo City Hospital, Kamihongo - 4005, Chiba 271-8511, Japan.
Morishita
Mariko
M
Katsuta
Hideo
H
Hosoda
Shoji
S
Shinomiya
Katsuhiko
K
Noro
Masahiro
M
Nagai
Tsuneji
T
Takayama
Kozo
K
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D003505:Cyclodextrins / Q000737:chemistry / Q000633:toxicity*; D008297:Male; D008745:Methylation; D008860:Microscopy, Ultraviolet; D009297:Nasal Mucosa / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D009300:Nasal Septum / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009994:Osmolar Concentration; D014677:Pharmaceutical Vehicles; D000077423:Polidocanol; D011092:Polyethylene Glycols / Q000737:chemistry / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014867:Water; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D014677:Pharmaceutical Vehicles; D047392:beta-Cyclodextrins; D014867:Water; D000077423:Polidocanol; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D011092:Polyethylene Glycols