Shang Yidan, Inthavong Kiao, Qiu Dasheng, Singh Narinder, He Fajiang, Tu Jiyuan
College of Air Transportation, Shanghai University of Engineering Science, Shanghai, China.
School of Engineering, RMIT University, Bundoora, VIC, Australia.
PLoS One. 2021 Jan 28;16(1):e0246007. doi: 10.1371/journal.pone.0246007. eCollection 2021.
Evaluation of nasal spray drug absorption has been challenging because deposited particles are consistently transported away by mucociliary clearance during diffusing through the mucus layer. This study developed a novel approach combining Computational Fluid Dynamics (CFD) techniques with a 1-D mucus diffusion model to better predict nasal spray drug absorption. This integrated CFD-diffusion approach comprised a preliminary simulation of nasal airflow, spray particle injection, followed by analysis of mucociliary clearance and drug solute diffusion through the mucus layer. The spray particle deposition distribution was validated experimentally and numerically, and the mucus velocity field was validated by comparing with previous studies. Total and regional drug absorption for solute radius in the range of 1 - 110nm were investigated. The total drug absorption contributed by the spray particle deposition was calculated. The absorption contribution from particles that deposited on the anterior region was found to increase significantly as the solute radius became larger (diffusion became slower). This was because the particles were consistently moved out of the anterior region, and the delayed absorption ensured more solute to be absorbed by the posterior regions covered with respiratory epithelium. Future improvements in the spray drug absorption model were discussed. The results of this study are aimed at working towards a CFD-based integrated model for evaluating nasal spray bioequivalence.
评估鼻喷雾剂药物吸收具有挑战性，因为在通过黏液层扩散过程中，沉积的颗粒会持续被黏液纤毛清除作用带走。本研究开发了一种将计算流体动力学（CFD）技术与一维黏液扩散模型相结合的新方法，以更好地预测鼻喷雾剂药物吸收。这种CFD-扩散综合方法包括对鼻腔气流、喷雾颗粒喷射的初步模拟，随后分析黏液纤毛清除作用以及药物溶质在黏液层中的扩散。通过实验和数值方法验证了喷雾颗粒沉积分布，并与先前研究对比验证了黏液速度场。研究了溶质半径在1 - 110nm范围内的总药物吸收和局部药物吸收。计算了喷雾颗粒沉积所贡献的总药物吸收。发现随着溶质半径增大（扩散变慢），沉积在前部区域的颗粒对吸收的贡献显著增加。这是因为颗粒不断从前部区域移出，延迟吸收确保了更多溶质被覆盖有呼吸上皮的后部区域吸收。讨论了喷雾药物吸收模型未来的改进方向。本研究结果旨在朝着基于CFD的评估鼻喷雾剂生物等效性的综合模型努力。
