The nasal absorption of macromolecules from powder formulations and the effect of sodium\ncarboxymethyl cellulose (CMC-Na) as a pharmaceutical excipient on their absorption were\nstudied. Model macromolecules were fluorescein isothiocyanate-labeled dextran (average\nmolecular weight of 4.4kDa, FD4) and insulin. The plasma concentration of FD4 after application\nof the powder containing 50% starch (control) was higher than that after application\nof the solution, and the absorption from 50% starch powder was enhanced by the substitution\nof starch with CMC-Na. The fractional absorption of FD4 after administration of the\nCMC-Na powder formulation was 30% and 40% higher than that after administration from\nthe solution and the starch powder, respectively. The nasal absorption of insulin from the\npowder and the effect of CMC-Na were similar with those of FD4. The effective absorption\nof FD4 and insulin after application of powder with CMC-Na could be due to the increase in\nthe nasal residence of FD4 and insulin. No damage in the nasal mucosa or dysfunction of\nthe mucociliary clearance was observed after application of the drug powder and CMC-Na.\nThe present findings indicate that nasal delivery of powder formulations with the addition of\nCMC-Na as an excipient is a promising approach for improving the nasal absorption of\nmacromolecules.
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