P-146 Pulsating aerosols allow topical rhinosinusitis therapy

Rationale: Although there is a high incidence of nasal disorders including chronic sinusitis, there is limited success in topical drug delivery to the nose and the paranasal cavities/sinuses. This is caused by the nose being an efficient filter for inhaled aerosol particles and the paranasal sinuses being virtually non ventilated. Objectives: Sinus ventilation was visualized in a human nasal cast and in three healthy human volunteers using dynamic 81mKr-gas gamma camera imaging in combination with pulsating airflows. Furthermore, deposition and retention of 99mTc-DTPA radiolabelled aerosol was assessed. Results: In the nasal cast ventilation efficiency of the sinuses was increased more than fivefold compared to a delivery regime without pulsation. Up to 8% of the aerosolized drug was deposited into the paranasal sinuses whereas only 0.2% deposition was achieved without pulsation. Efficient ventilation of the paranasal sinuses was confirmed in human healthy volunteers applying a pulsating airflow and this was associated with a drug deposition of up to 5%. Surprisingly, nasal clearance kinetics of the drug was reduced and associated with an up to twofold longer residence time of the drug at the site of deposition. Conclusions: Our data support the hypothesis that topical drug delivery in relevant quantities to the nose and paranasal sinuses is possible using pulsating airflows. Due to a delayed clearance, the frequency of drug applications can be reduced.