Effects of absorption enhancers on rat nasal epithelium in vivo: release of marker compounds in the nasal cavity.
OBJECTIVE
The assessment of the effects of nasal absorption enhancers on the rat nasal epithelium and membrane permeability in vivo after a single nasal dose of the enhancers.


METHODS
The release of marker compounds (protein, cholesterol and acid phosphatase) from the nasal epithelium was measured using a lavage technique. The nasal membrane permeability was determined after intravenous administration of a systemic tracer (FITC-albumin).


RESULTS
The effects of the absorption enhancers could be classified into four categories. The first consisted of HP beta CD (5%), DM beta CD (2%) and RAMEB (2%) and was not different from the control (physiological saline). For the second category, DM beta CD (5%), effects were significantly higher than for the control. The third category, SGC (1%), was more active than DM beta CD (5%) but less active than the last group. The fourth, most membrane damaging, category consisted of STDHF (1%), laureth-9 (1%) and LPC (1%). Administration of these three enhancers also resulted in release of acid phosphatase, indicating that severe membrane damage occurred. The release of cholesterol from nasal epithelium was largely dependent on the cholesterol solubilisation of the absorption enhancers. The amount of cholesterol released by laureth-9 and LPC was the largest.


CONCLUSIONS
The results of this in vivo study are in agreement (i.e. similarity in rank order) with morphological and ciliotoxicity studies of nasal absorption enhancers, demonstrating that this in vivo model is a valuable tool to classify nasal absorption enhancers according to their effects on the rat nasal epithelium.
D000042:Absorption; D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D002784:Cholesterol / Q000378:metabolism; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005079:Excipients / Q000494:pharmacology*; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D008297:Male; D009296:Nasal Cavity / Q000378:metabolism; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D015415:Biomarkers; D005079:Excipients; D005456:Fluorescent Dyes; D011506:Proteins; D002784:Cholesterol; D000135:Acid Phosphatase; D016650:Fluorescein-5-isothiocyanate