Computational Fluid Dynamics Approach for Direct Nose-to-Brain Drug Delivery: A Systematic Review and Meta-Analysis.

Background/Objectives: Optimizing drug deposition to the olfactory region is key in Nose-to-brain drug delivery strategies. However, findings from computational fluid dynamics (CFD) studies remain inconsistent concerning the parameters influencing olfactory deposition, limiting clinical translation and device optimization. This systematic review aims to identify robust CFD parameters for optimizing drug delivery to the olfactory region. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines, selecting studies reporting CFD simulations of nasal drug delivery with evaluation of olfactory deposition efficiency. The primary outcome was the correlation between each CFD parameter and olfactory deposition rate. Parameters included particle size, impaction parameter, flow rate, spray cone angle, insertion angle, injection velocity, head position, release position, and breathing pattern. Data were extracted and standardized, and statistical methods were used to assess correlations, heterogeneity, and potential biases in study results. Results: Smaller particle size (pooled r = -0.42) and lower impaction parameter (r = -0.39) were significantly associated with higher olfactory deposition. No consistent correlation was observed with breathing flow rate. Heterogeneity across studies was high (I2 > 90%). Funnel plots asymmetry suggested potential publication bias in particle-related outcomes. Conclusions: Particle characteristics, especially size and inertia, are the most critical determinants of olfactory deposition in CFD simulations. These findings support design optimization of nasal delivery devices targeting the olfactory region and underscore the need for standardized reporting and validation across CFD studies.