Purpose Enhancement of intra-nasal sinus drug deposition involves nebulization of a drug superimposed by the acoustic airflow characterized by a specific frequency. We investigated the impact of fixed frequency versus frequency sweep acoustic airflow on the improvement of aerosolized drug penetration into the maxillary sinuses. Methods Fixed frequency and frequency sweep acoustic airflow were generated using a prototype of variable frequency nebulizing system, and their effect on the intra-nasal sinus aerosol deposition in a ‘nasal replica’, a transparent, water-resistant, non-porous resin replica of the human plastinated cast created using a stereolithography technique, was tested. Sodium fluoride and gentamicin were chosen as markers. In addition to this, the effect of sweep cycle and intensity variation was also studied. Results Studies performed using fixed frequency acoustic airflow showed that each of the maxillary sinuses of the ‘nasal replica’ required specific frequency for the optimal intra-nasal sinus aerosol deposition; depending on the ostia of the left and right maxillary sinuses which are different. Intra-nasal sinus drug deposition experiments under the effect of the frequency sweep acoustic airflow showed an optimal aerosol deposition into both maxillary sinus of the ‘nasal replica’. Studies on the effect of the duration of the sweep cycle showed that the shorter the cycle the better the deposition. Conclusion Our study demonstrates the benefit of frequency sweep acoustic airflow on the drug deposition into maxillary sinuses of the ‘nasal replica’ characterized by ostia of different geometry. However, the delivery rates of the ‘nasal replica’ cannot be directly applied to real human chronic rhinosinusitis condition; further in vivo studies have to be conducted.