Use Of Reconstructed Tissue And 3D Printed Ct-based Nasal Casts For The Assessment Of Nasal Delivery

This research explores improved in vitro models for nasal drug delivery using Reconstructed Nasal Epithelium (RNE) and CT-based 3D printed nasal casts. Traditional models, such as excised animal tissue and idealized airflow casts, have significant limitations—animal tissues are nonviable and variable, while physical casts may allow misleading formulation behavior due to non-adhesive surfaces and unrealistic anatomy.

RNE models are developed from primary human nasal epithelial cells sourced from healthy mid-turbinate tissue. These cells are cultured to full differentiation, forming tight junctions, mucus layers, cilia, and maintaining metabolic activity. This allows RNE to better simulate the in vivo nasal barrier. Studies comparing RNE to ovine mucosa showed that only RNE produced statistically significant differences between formulations and provided more nuanced insights into early drug absorption—critical for nasal delivery.

CT-based nasal casts further enhance delivery assessment by allowing detailed anatomical replication and region-specific segmentation. These 3D printed models accommodate material optimization to match drug/excipient compatibility and can simulate breathing conditions when attached to an artificial lung. Experiments using these casts demonstrated region-specific delivery, with formulation and material type significantly affecting distribution outcomes.

Together, these tools address gaps in nasal drug delivery modeling by improving predictive performance, enabling better formulation screening, and reducing development risk. The combined use of RNE and anatomically correct nasal casts presents a more reliable platform for understanding distribution, permeation, and clearance—offering valuable insight during early-stage drug development. These advancements contribute to safer, more effective nasal therapies and streamlined translation from bench to clinic.