Is the use of benzalkonium chloride as a preservative for nasal formulations a safety concern? A cautionary note based on compromised mucociliary transport

Background: Topical nasal solution and suspension delivery systems are avai lable for short- and long-acting vasoconstrictors, ipratropium, cromolyn, a zelastine, and glucocorticosteroids. The use of intranasal glucocorticoster oids has increased substantially because the efficacy of these agents has b een well established for the treatment of perennial and seasonal allergic r hinitis, Adverse local effects of burning, irritation, and dryness are occa sionally associated with glucocorticosteroid nasal preparations. Benzalkoni um chloride (BKC) is a quaternary ammonium antimicrobial agent included in some nasal solutions (including glucocorticosteroids) to prevent the growth of bacteria, Some reports suggest that BKC in nasal sprays may cause adver se effects, including reduced mucociliary transport, rhinitis medicamentosa , and neutrophil dysfunction. Objective: This article summarizes recent literature about possible adverse biologic effects associated with BKC as a nasal spray preservative by exam ining its effects on the following properties of mucociliary transport: cil iary motion, ciliary form, ciliary beat frequency, electron microscopy, and particle movement/saccharin clearance tests. Conclusion: Both animal and human in vitro data suggest that BKC promotes c iliostasis and reduction in mucociliary transport that may be partially mas ked by absorption and dilution effects occurring in respiratory mucus. Thes e possible confounding factors may account for several disparate human in v ivo results. The use of BKC-free glucocorticosteroid formulations should be considered, particularly in patients who complain of nasal burning, drynes s, or irritation.