Reestablishment of the nasal permeability barrier to several peptides following exposure to the absorption enhancer tetradecyl-beta-D-maltoside.
Regular insulin, NPH insulin, glargine insulin, calcitonin, and human growth hormone were administered to rats nasally with 0.125% tetradecyl-beta-D-maltoside (TDM), or at various times after TDM treatment. Absorption of all five peptides was enhanced initially and diminished in a time-dependent manner as the interval between administration of TDM and the peptide increased. Changes in nasal morphology were also assessed via transmission electron microscopy (TEM) immediately after TDM treatment and at various times thereafter. TEM analysis demonstrated that 0.125% TDM caused a rapid and transient alteration in the morphology of the apical membrane surface. Fewer cilia were observed and cell-cell junctions were difficult to visualize, but no epithelial cell erosion was apparent. Two hours after TDM treatment, the apical membrane surface once again contained abundant cilia and cell-cell junctions were readily visualized. The complete recovery of the nasal permeability barrier to several different peptides following TDM administration and the concomitant histological evidence demonstrate that TDM treatment transiently perturbs the nasal mucosa to stimulate peptide drug absorption and does not produce irreversible damage to the cells that line the nasal cavity.
Arnold
John J
JJ
Samford University McWhorter School of Pharmacy, 800 Lakeshore Drive, Birmingham, Alabama 35229, USA. jarnold@samford.edu
Fyrberg
Michael D
MD
Meezan
Elias
E
Pillion
Dennis J
DJ
D000042:Absorption / Q000187:drug effects; D000281:Administration, Intranasal; D000818:Animals; D002116:Calcitonin / Q000008:administration & dosage / Q000493:pharmacokinetics; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D008297:Male; D008320:Maltose / Q000031:analogs & derivatives* / Q000494:pharmacology; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D010455:Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007328:Insulin; D010455:Peptides; C459187:tetradecyl maltoside; D019382:Human Growth Hormone; D008320:Maltose; D002116:Calcitonin