Permeation of polysucrose 15000 across the human nasal mucosa in vivo.
Studies of the nasal permeation of small molecules (< 1000 Da) have yielded important information about the integrity of the human airway mucosa 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 nasal cavity of 12 healthy nonatopic subjects by employment of a nasal-pool device. Permeation as determined by the 24-h urine recovery of PS (micro-ELISA analysis assay) was expressed as percentage of nasal instillate. Mean baseline permeation was 0.044% (range 0.009-0.250%). In the presence of the detergent, permeation increased to 0.600% (range 0.007-2.260%) (P < 0.01). After oral intake of 750 mg of PS 15,000 (50 micrograms/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 15,000, an elevated permeation rate in the presence of an epithelium-damaging detergent molecule, and a negligible permeation by the oral route. These properties support the utility of PS 15,000 as a nasal airway permeation tracer. Its size further suggests that its permeation may reflect mucosal perviousness to many allergens.
Andersson
M
M
Department of Otorhinolaryngology Head and Neck Surgery, University Hospital, Lund, Sweden.
Greiff
L
L
Oman
H
H
Svensson
C
C
Wollmer
P
P
Persson
C G
CG
D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008970:Molecular Weight; D009297:Nasal Mucosa / Q000378:metabolism*; D010539:Permeability; D011108:Polymers / Q000493:pharmacokinetics*; D013395:Sucrose / Q000493:pharmacokinetics*
D011108:Polymers; C104306:polysucrose 15000; D013395:Sucrose