Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 99, Issue 4, Pages 1912-1920Publisher
JOHN WILEY & SONS INC
DOI: 10.1002/jps.21977
Keywords
insulin; drug delivery; calcitonin; growth hormone; nasal; alkylglycosides
Funding
- National Institute of Environmental Health Sciences [ES08933]
- University of Alabama at Birmingham
- National Institutes of Health [DK079626]
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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. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:1912-1920, 2010
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