Correlation of tetradecylmaltoside induced increases in nasal peptide drug delivery with morphological changes in nasal epithelial cells

The effect of tetradecylmaltoside (TDM) on nasal peptide drug absorption was assessed with four peptides of distinct molecular size: insulin (5.7 kDa), leptin (16 kDa), somatropin (22.1 kDa), and epoetin alfa (30.4 kDa). The nasal uptake of the smallest peptides, insulin and leptin, was significantly increased at a TDM concentration of only 0.06%. The uptake of somatropin was significantly increased when concentrations of 0.125% or more were used. The uptake of the largest peptide, epoetin alfa, was not significantly increased, in the presence of 0.125-0.5% TDM. Light microscopy revealed that formulations containing 0.125% TDM caused moderate alterations in nasal epithelial cell morphology, while higher concentrations of TDM (0.5%), caused more extensive morphological changes. Following treatment with 0.125% TDM, the distribution of cilia was altered and the number of pinocytotic vesicles was increased, at a time that correlated with increased nasal absorption of insulin. Consistent with these findings, FITC-insulin applied nasally in the absence of TDM did not enter nasal epithelial cells, whereas FITC-insulin co-administered with 0.125% TDM was internalized into the cells, with a uniform distribution, consistent with transcellular movement of the peptide through the cells. (C) 2004 Wiley-Liss, Inc. and the American Pharmacists Association.