Design and evaluation of cyanocobalamin nasal powders for nasal delivery using biomimetic nasal cavity models

For intranasal administration, biomimetic evaluation in vitro plays a unique role in visualizing drug deposition in the nasal cavity, guiding the pharmacokinetic test. In this study, cyanocobalamin (Vitamin B₁₂, VB₁₂) nasal powders were developed and evaluated based on the biomimetic rat and human nasal models. Hydroxypropyl-β-cyclodextrin (HP-β-CD) was selected as a carrier to improve photostability and thermal stability of VB₁₂. The nasal mucosal permeation study confirmed the permeation promotion of HP-β-CD to VB₁₂. To assess nasal deposition patterns, three-dimensional (3D) printed rat and human nasal cavity models were developed based on computed tomography (CT) images. The rat nasal cavity model was also used to evaluate self-designed nozzles tailored to nasal cavity structures, which significantly reduced tracheal deposition when administered at an optimized angle. In the rat nasal cavity model, the powders were primarily deposited in the olfactory zone (38.85 ± 3.90%), while in the human nasal cavity model, deposition was predominantly in the respiratory zone (69.12 ± 6.38%). Pharmacokinetics in rats showed that the nasal powders exhibited good bioavailability (36.45%) compared with nasal and gavage solutions. Additionally, nasal cavity drug retention studies indicated superior retention of the nasal powder compared with the VB₁₂ nasal solution. In summary, VB₁₂ nasal powder was visualized using 3D biomimetic nasal models and effectively delivered to the nasal cavity in rats, providing a reference for evaluating nasal powder and other nasal dosage forms.