Prediction of nasal spray drug absorption influenced by mucociliary clearance.
Prediction of nasal spray drug absorption influenced by mucociliary clearance.
复制标题
粘膜纤毛清除率影响鼻喷雾药物吸收的预测
DOI：
10.1371/journal.pone.0246007
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Tu J
中科院分区：
文献类型：
--
作者：
Shang Y;Inthavong K;Qiu D;Singh N;He F;Tu J
鼻喷雾剂药物吸收的评价一直具有挑战性，因为沉积的颗粒在扩散通过粘液层期间通过粘膜纤毛清除而持续地被转运走。这项研究开发了一种新的方法，结合计算流体动力学（CFD）技术与1-D粘液扩散模型，以更好地预测鼻腔喷雾剂药物吸收。该集成CFD扩散方法包括鼻气流的初步模拟、喷雾颗粒注射，然后分析粘膜纤毛清除率和药物溶质通过粘液层的扩散。通过实验和数值模拟验证了喷雾颗粒沉积分布，并通过与前人研究的对比验证了粘液速度场。研究了溶质半径在1 - 110 nm范围内的总吸收和局部吸收。计算由喷雾颗粒沉积贡献的总药物吸收。发现沉积在前部区域上的颗粒的吸收贡献随着溶质半径变大（扩散变慢）而显著增加。这是因为颗粒始终从前部区域移出，延迟吸收确保更多溶质被呼吸上皮覆盖的后部区域吸收。对喷雾药物吸收模型的改进进行了讨论。本研究的结果旨在建立一个基于CFD的鼻喷雾剂生物等效性评价模型。
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.
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影响因子：
3.7
作者：
Rygg, Alex;Hindle, Michael;Longest, P. Worth
通讯作者：
Longest, P. Worth
影响因子：
2.3
作者：
Abouali, Omid;Keshavarzian, Erfan;Bagheri, Mohammad Hadi
通讯作者：
Bagheri, Mohammad Hadi
影响因子：
3.4
作者：
Olmsted, SS;Padgett, JL;Cone, RA
通讯作者：
Cone, RA
DOI：
10.1089/jam.2006.19.301
发表时间：
2006-09-01
期刊：
JOURNAL OF AEROSOL MEDICINE-DEPOSITION CLEARANCE AND EFFECTS IN THE LUNG
影响因子：
--
作者：
Schroeter, Jeffry D.;Kimbell, Julia S.;Asgharian, Bahman
通讯作者：
Asgharian, Bahman
DOI：
10.1089/jamp.2015.1252
发表时间：
2016-10
影响因子：
3.4
作者：
Rygg A;Longest PW
通讯作者：
Longest PW