Topical drug delivery: how CFD can revolutionize the usage protocol for nasal sprays

Topical delivery is meant to provide high concentrations of drugs to nasal mucosal surfaces, with sprays being the most frequently prescribed treatment. However, these potent drugs are often ineffective, in part owing to deficient transport. Patients are typically instructed in the use of spray devices by the physicians and the package inserts; a protocol we refer to as "current use (CU)". We have quantified the CU drug delivery, through Fluent-based CFD simulations in anatomically realistic respiratory models. These numbers are compared against our innovation of "line-of-sight (LoS)" protocol, developed by re-orienting the spray axis towards specific anatomic landmarks. Analysis on five airway models indicates an average seven-fold increase in drug transport to nasal targets, while using LoS. To verify robustness of this discovery, we considered release zones close to the LoS and the CU points, and still spray release around LoS resulted in better drug transmission compared to that around CU. The improvement was statistically significant with p-values less than 0.05, both for t-tests and Wilcoxon signed-rank tests. Experiments in 3D-printed replicates have validated the CFD results. Our findings will help advance therapeutics for sinonasal ailments.