Acute histopathological effects of benzalkonium chloride and absorption enhancers on rat nasal epithelium in vivo

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Abstract

The aim of the study was to determine the acute effects of nasal absorption enhancers on the morphology of the rat nasal epithelium in vivo. Examples of three classes of enhancers were studied: the cyclodextrins dimethyl-β-cyclodextrin 2% (w/v) and randomly methylated-β-cyclodextrin 2% (w/v), the bile salt sodium glycocholate 1% (w/v) and the phospholipid L-α-lysophosphatidylcholine 1% (w/v). The preservative 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 min the nasal cavity was fixated with Bouin and the tissue was processed 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 located in the respiratory epithelium. The effects of randomly methylated β-cyclodextrin and dimethyl-β-cyclodextrin were also minor and comparable to those of physiological saline. After administration of sodium glycocholate, large amounts of mucus were discharged from goblet cells and pyknosis occurred. L-α-lysophosphatidylcholine resulted in disruption of the epithelium, and damage was found not only in the respiratory epithelium but also in the olfactory epithelium. In conclusion, the acute effects of methylated β-cyclodextrins on the nasal epithelium morphology are relatively mild, and comparable to or less than those of the preservative benzalkonium chloride. Sodium glycocholate shows irreversible damage, and L-α-lysophosphatidylcholine is the most damaging absorption enhancer.

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Marttin, E., Verhoef, J. C., Romeijn, S. G., Zwart, P., & Merkus, F. W. H. M. (1996). Acute histopathological effects of benzalkonium chloride and absorption enhancers on rat nasal epithelium in vivo. International Journal of Pharmaceutics, 141(1–2), 151–160. https://doi.org/10.1016/0378-5173(96)04632-7

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