Supplementary data for "Mechanics-guided parametric modeling of intranasal spray devices and formulations for targeted drug delivery to the nasopharynx"

Improving the performance of nasal sprays through optimization of key device and formulation parameters, such as the formulation density, spray cone angle, and sprayed droplet sizes—is hypothesized to be an effective strategy to enhance deposition efficiency at target tissue sites along the airway, marked for their proclivity for the initial onset of infection. This study identifies the nasopharynx, a primary locus of early viral entry, as the optimal target for intranasal drug delivery. Three-dimensional anatomical geometries reconstructed from high-resolution computed tomography scans were employed to evaluate a cone injection approach, considering monodispersed sprayed particle sizes between 10 – 50 μm, six formulation densities ranging from 1.0 – 1.5 g/ml, and twelve plume angles spanning 15^◦ – 70^◦. Large Eddy Simulation mimicking the inhaled airflow within the anatomical domains was coupled with a Lagrangian particle-tracking framework to derive the drug deposition trend. The resulting three-dimensional deposition contour map revealed that nasopharyngeal deposition was maximized for droplet sizes of 25 – 45 μm and plume angles ≤ 30^◦, when the nasopharyngeal deposition rates are averaged across all the test airway geometries and formulation densities. In addition, the formulation density of 1.0 g/ml yielded the highest mean deposition rate, over the tested range of sprayed particle sizes and plume angles. The findings collectively demonstrate that rational optimization of intranasal spray design is achievable and can substantially enhance targeted drug delivery to the nasopharynx, thereby aiding in the mitigation of airway diseases.

通过优化关键装置与制剂参数（如制剂密度、喷雾锥角及喷射液滴尺寸）以提升鼻用喷雾性能，被认为是增强药物在气道靶组织部位沉积效率的有效策略——这类靶组织正是感染初始发作的好发部位。本研究将鼻咽——病毒早期侵入的主要位点——确定为鼻内给药的最优靶标。研究采用基于高分辨率计算机断层扫描（computed tomography，CT）重建的三维解剖几何模型，对锥形喷射方案开展评估，实验设置了10–50 μm的单分散喷射粒径、6种覆盖1.0–1.5 g/ml范围的制剂密度，以及12种跨度为15°–70°的喷雾羽流角度。将模拟解剖域内吸入气流的大涡模拟（Large Eddy Simulation）与拉格朗日粒子追踪框架（Lagrangian particle-tracking framework）相结合，以推导药物沉积趋势。所得三维沉积等高线图显示，当对所有测试气道几何模型与制剂密度下的鼻咽沉积率取平均值时，粒径25–45 μm、羽流角度≤30°的条件下，鼻咽沉积量达到最大。此外，在所测试的喷射粒径与羽流角度范围内，1.0 g/ml的制剂密度可获得最高的平均沉积率。综上，本研究结果表明，鼻用喷雾设计的合理优化具备可行性，可大幅提升鼻咽部位的靶向给药效率，从而助力气道疾病的防控。