Targeted drug delivery to the deviated regions of the human nasal cavities: An in silico investigation and in vitro validation

Abstract

Background and Objective

Delivering drugs to the deviated regions in patients with nasal septal deviation is vital for the treatment but challenging due to the complex shape of the nasal cavity and the intersubject variability in the nasal anatomies. While previous studies have focused on drug delivery to standard areas like the olfactory region, none have specifically looked at how drugs are deposited in the deviated regions. The current study numerically investigates six drug administration parameters aiming to control and maximize drug deposition in the deviated regions of the nasal cavity in three types of septal deviations.

Methods

Three-dimensional models are created using CT scans from three patients, with S-shaped, C-shaped, and reverse C-shaped septal deviations, and the deviated regions are identified by the detailed slice-by-slice inspection method. Eulerian and Lagrangian simulations are performed for the fluid flow and drug delivery, incorporating all six drug administration parameter variations. Further, in-house experiments are performed on a three-dimensional printed transparent nasal cavity to validate the pressure drop and drug deposition patterns.

Results

It is observed that increasing the spray half-cone angle decreases the targeted deposition in the C, reverse C, and left side of the S-shaped models. On the contrary, a wider half-cone angle (20°) and cone radius (2 mm) enhances targeted deposition on the right side of the S-shaped model. The ideal particle size range for all models is 10 to 16 µm. Lower initial particle velocities (1 m/s and 3 m/s) lead to maximum targeted deposition in the C and left side of the S-shaped models, while higher ones (14 m/s and 8m/s) enhance targeted deposition in the reverse C and right side of the S-shaped model, respectively. Optimized administration angles accurately direct particles to deviated regions, with patient-specific adjustments achieving better outcomes. Increased flow rates enhance both total and targeted depositions. Head orientation adjustments are effective for deviations in the middle and lower regions but have a limited impact when deviation presents in the anterior regions.

Conclusions

The study's findings help unveil the effective targeted drug delivery strategies, provide insights for the better design of the nasal spray device, and improve personalized treatment efficacy for patients with septal deviations.