PERMEATION OF POLYSUCROSE 15,000 ACROSS THE HUMAN NASAL-MUCOSA IN-VIVO

Studies of the nasal permeation of small molecules (<1000 Da) have yie lded important information about the integrity of the human airway muc osa in health and disease. In this study, we used a much larger tracer molecule, polysucrose (PS) 15 000 (approx. 14 700 Da), to predict the mucosal permeation of inhalational allergens. PS 15 000 (50 mg/ml; 15 ml), with or without a detergent type of permeation enhancer (dioctyl sodium sulfosuccinate 10 mg/ml), was maintained for 15 min in one nas al cavity of 12 healthy nonatopic subjects by employment of a nasal-po ol device. Permeation as determined by the 24-h urine recovery of PS ( micro-ELISA analysis assay) was expressed as percentage of nasal insti llate. Mean baseline permeation was 0.044% (range 0.009-0.250%). In th e presence of the detergent, permeation increased to 0.600% (range 0.0 07-2.260%) (P<0.01). After oral intake of 750 mg of PS 15 000 (50 mu g /ml; 15 ml), the 24-h urinary recovery was 0.013% (range 0.004-0.023%) . Our study thus demonstrates a measurable baseline permeation of PS 1 5 000, an elevated permeation rate in the presence of an epithelium-da maging detergent molecule, and a negligible permeation by the oral rou te. These properties support the utility of PS 15 000 as a nasal airwa y permeation tracer. Its size further suggests that its permeation may reflect mucosal perviousness to many allergens.