ACUTE HISTOPATHOLOGICAL EFFECTS OF BENZALKONIUM CHLORIDE AND ABSORPTION ENHANCERS ON RAT NASAL EPITHELIUM IN-VIVO

The aim of the study was to determine the acute effects of nasal absor ption enhancers on the morphology of the rat nasal epithelium in vivo. Examples of three classes of enhancers were studied: the cyclodextrin s dimethyl-beta-cyclodextrin 2% (w/v) and randomly methylated-beta-cyc lodextrin 2% (w/v), the bile salt sodium glycocholate 1% (w/v), and th e phospholipid L-alpha-lysophosphatidylcholine 1% (w/v). The preservat ive benzalkonium chloride 0.01% (w/v) was investigated for reasons of comparison. The compounds were dissolved in physiological saline (0.9% NaCl) and administered intranasally to anaesthetized rats. After 15 m in the nasal cavity was fixated with Bouin and the tissue was processe d for light microscopic examination. Morphological changes induced by physiological saline were graded as negligible or minor, and those of benzalkonium chloride as minor to major. The effects were mainly locat ed in the respiratory epithelium. The effects of randomly methylated b eta-cyclodextrin and dimethyl-beta-cyclodextrin were also minor and co mparable to those of physiological saline. After administration of sod ium glycocholate, large amounts of mucus were discharged from goblet c ells and pyknosis occurred. L-alpha-lysophosphatidylcholine resulted i n disruption of the epithelium, and damage was found not only in the r espiratory epithelium but also in the olfactory epithelium. In conclus ion, the acute effects of methylated beta-cyclodextrins on the nasal e pithelium morphology are relatively mild, and comparable to or less th an those of the preservative benzalkonium chloride. Sodium glycocholat e shows irreversible damage, and L-alpha-lysophosphatidylcholine is th e most damaging absorption enhancer.