EFFECTS OF ABSORPTION ENHANCERS ON RAT NASAL EPITHELIUM IN-VIVO - RELEASE OF MARKER COMPOUNDS IN THE NASAL CAVITY

Purpose. The assessment of the effects of nasal absorption enhancers o n the rat nasal epithelium and membrane permeability in vivo after a s ingle nasal dose of the enhancers. Methods. The release of marker comp ounds (protein, cholesterol and acid phosphatase) from the nasal epith elium was measured using a lavage technique. The nasal membrane permea bility was determined after intravenous administration of a systemic t racer (FITC-albumin). Results. The effects of the absorption enhancers could be classified into four categories. The first consisted of HP b eta D (5%), DM beta CD (2%) and RAMEB (2%) and was not different from the control (physiological saline). For the second category, DM beta C D (5%), effects were significantly higher than for the control. The th ird category, SGC (1%), was more active than DM beta CD (5%) but less active than the last group. The fourth, most membrane damaging, catego ry consisted of STDHF (1%), laureth-9 (1%) and LPC (1%). Administratio n of these three enhancers also resulted in release of acid phosphatas e, indicating that severe membrane damage occurred. The release of cho lesterol from nasal epithelium was largely dependent on the cholestero l solubilisation of the absorption enhancers. The amount of cholestero l released by laureth-9 and LPC was the largest. Conclusions. The resu lts of this in vivo study are in agreement (i.e. similarity in rank or der) 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.