A fluid and particle mechanics perspective of nasal drug delivery.

Introduction: Intranasal drug delivery offers a noninvasive, rapid, and metabolically advantageous route for local and systemic therapies. However, achieving targeted and efficient delivery remains a significant challenge due to the nasal cavity's complex anatomy, protective airflow structures, and physiological variability. Traditional focus on formulation chemistry overlooks the critical role of fluid and particle dynamics in determining drug fate.

Areas covered: This review synthesizes decades of research on nasal drug delivery with a focus on biophysical and aerodynamic considerations. The literature review covered clinical studies, CFD investigations, and emerging device innovations. The article progresses from clinical targets and barriers (anatomical and human factors) to particle-fluid dynamics governing deposition, leading into advances in experimental and computational models to understand how to overcome these barriers, culminating in translational insights and future directions.

Expert opinion: Patient-specific, GPU-accelerated CFD simulations, increasingly refined by AI, will enable predictive deposition mapping and integration with PBPK models. This supports in silico trials and personalized device optimization, yet clinical translation is limited by validation gaps, regulatory conservatism, and manufacturing complexities. Future integration of real-time imaging, AI surrogates, and smart delivery systems may shift nasal drug delivery toward per-nostril precision medicine and virtual-cohort-based regulatory acceptance.