基于计算流体动力学的深部插入鼻腔递送用于精准鼻窦靶向

文献信息

中文摘要

传统鼻腔喷雾递送存在靶向性差的问题，大多数颗粒沉积于鼻腔前部区域，导致治疗效果不足、所需剂量增加以及副作用风险升高。本研究定量评估了鼻腔喷雾性能，并评价了深部插入与浅部插入的获益。采用标准化的三维健康鼻腔模型和计算流体动力学，将雷诺平均纳维-斯托克斯k-ω湍流模型与双向耦合离散相模型相结合。通过1144个测试案例，系统研究了关键喷雾参数，包括喷射速度、锥角、颗粒释放位置、喷射方向、粒径分布、插入深度和呼吸流量。根据额窦、上颌窦、筛窦和蝶窦开口的临床重要性定义目标区域。鼻阀后方的深部插入显著增强了药物向鼻窦靶区的转运。与浅部插入相比，深部递送将总目标沉积效率从4.4%提高至44.9%，并降低了对操作误差的敏感性，变异系数至少降低60%。改善的主要机制是减少了无效的前部沉积。深部鼻腔喷雾递送显著改善了药物向鼻窦的靶向性，并增强了对使用者操作变异的稳健性。增加递送深度的策略在提高治疗效果、降低所需剂量以及减少鼻腔和鼻窦疾病副作用风险方面显示出强大潜力。

英文摘要

Traditional nasal spray delivery suffers from poor targeting, with most particles depositing in anterior nasal regions, leading to insufficient therapeutic effects, higher dosage requirements, and increased side effect risks. This study quantitatively evaluated nasal spray performance and assessed the benefits of deep versus shallow insertion. A standardized three-dimensional healthy nasal cavity model and computational fluid dynamics were employed, combining the Reynolds-averaged Navier-Stokes k- ω turbulence model with a two-way coupled discrete phase model. Key spray parameters including injection velocity, cone angle, particle releasing position, injection direction, particle size distribution, insertion depth, and respiratory flow rate, were systematically investigated through 1144 test cases. Target regions were defined based on the clinical importance of the frontal, maxillary, ethmoid, and sphenoid sinus ostia. Deep insertion posterior to the nasal valve markedly enhanced drug transport to sinus targets. Compared with shallow insertion, deep delivery increased total target deposition efficiency from 4.4% to 44.9% and reduced sensitivity to operational errors, with coefficients of variation decreasing by at least 60%. The primary mechanism of improvement was the reduction of ineffective anterior deposition. Deep nasal spray delivery significantly improves drug targeting to the sinuses and enhances robustness against user operational variability. Strategies that increase delivery depth show strong potential to improve therapeutic effectiveness, reduce required dosages, and lower side effect risks for nasal and sinus conditions.