{"title":"合成黏液对3d打印SLA鼻腔模型喷雾沉积影响的定量研究。","authors":"Amr Seifelnasr, Xiuhua April Si, Jinxiang Xi","doi":"10.1007/s11095-025-03886-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>To quantify the deposition distribution of intranasally administered sprays in an anatomically accurate 3D-printed nasal model under varying conditions.</p><p><strong>Methods: </strong>A multipiece nasal cast was used to assess deposition under three head positions (upright, 22.5° backward tilt, and 45° backward tilt) and two airflow conditions (no flow and gentle sniff). Synthetic mucus coatings were prepared using saline-based xanthan gum (XG) solutions with two different XG concentrations: 0.25% w/v, representing a healthy state, and 1% w/v, representing a diseased state. Regional doses were quantified using salinity-based measurements for both uncoated and coated nasal casts.</p><p><strong>Results: </strong>The results demonstrate that synthetic mucus coatings significantly altered intranasal spray dosimetry, promoting broader spreading and deeper translocation compared to dry-wall models. In the middle turbinate region, the highest mean deposition occurred under sniff airflow at a 45° backward tilt with a 1% XG coating (76 ppm), representing a 244% increase over the dry condition (22 ppm). For the posterior nasal cavity, the most effective mean deposition was achieved at a 22.5° backward tilt with sniff airflow and a 0.25% XG coating (63 ppm vs. 0 ppm dry). The mucus viscosity can significantly alter regional distribution. A 0.25% XG coating facilitated deeper translocation to the posterior nasal cavity, while 1% XG enhanced retention in the middle turbinate region.</p><p><strong>Conclusions: </strong>These findings highlight the importance of incorporating synthetic mucus in in vitro nasal models to improve physiological relevance and provide insights for optimizing intranasal drug delivery techniques.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Quantitative Investigation of Synthetic Mucus Effects on Spray Deposition in a 3D-Printed SLA Nasal Cavity Model.\",\"authors\":\"Amr Seifelnasr, Xiuhua April Si, Jinxiang Xi\",\"doi\":\"10.1007/s11095-025-03886-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>To quantify the deposition distribution of intranasally administered sprays in an anatomically accurate 3D-printed nasal model under varying conditions.</p><p><strong>Methods: </strong>A multipiece nasal cast was used to assess deposition under three head positions (upright, 22.5° backward tilt, and 45° backward tilt) and two airflow conditions (no flow and gentle sniff). Synthetic mucus coatings were prepared using saline-based xanthan gum (XG) solutions with two different XG concentrations: 0.25% w/v, representing a healthy state, and 1% w/v, representing a diseased state. Regional doses were quantified using salinity-based measurements for both uncoated and coated nasal casts.</p><p><strong>Results: </strong>The results demonstrate that synthetic mucus coatings significantly altered intranasal spray dosimetry, promoting broader spreading and deeper translocation compared to dry-wall models. In the middle turbinate region, the highest mean deposition occurred under sniff airflow at a 45° backward tilt with a 1% XG coating (76 ppm), representing a 244% increase over the dry condition (22 ppm). For the posterior nasal cavity, the most effective mean deposition was achieved at a 22.5° backward tilt with sniff airflow and a 0.25% XG coating (63 ppm vs. 0 ppm dry). The mucus viscosity can significantly alter regional distribution. A 0.25% XG coating facilitated deeper translocation to the posterior nasal cavity, while 1% XG enhanced retention in the middle turbinate region.</p><p><strong>Conclusions: </strong>These findings highlight the importance of incorporating synthetic mucus in in vitro nasal models to improve physiological relevance and provide insights for optimizing intranasal drug delivery techniques.</p>\",\"PeriodicalId\":20027,\"journal\":{\"name\":\"Pharmaceutical Research\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-06-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmaceutical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11095-025-03886-4\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11095-025-03886-4","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
摘要
目的:量化不同条件下鼻内喷雾剂在解剖学上准确的3d打印鼻模型中的沉积分布。方法:采用多片鼻铸型在三种头位(直立、向后倾斜22.5°和向后倾斜45°)和两种气流条件(无气流和轻嗅)下评估沉积。用盐基黄原胶(XG)溶液制备合成黏液包被,XG浓度为0.25% w/v,代表健康状态,1% w/v代表患病状态。对未涂覆和涂覆鼻铸型采用基于盐度的测量来量化区域剂量。结果:结果表明,与干壁模型相比,合成黏液涂层显著改变了鼻内喷雾剂量测定,促进了更广泛的扩散和更深的易位。在中鼻甲区域,在45°向后倾斜的吸气气流和1% XG涂层(76 ppm)下,最高的平均沉积发生,比干燥条件(22 ppm)增加244%。对于后鼻腔,最有效的平均沉积是在向后倾斜22.5°,鼻腔气流和0.25%的XG涂层(63 ppm vs 0 ppm干燥)下实现的。黏液粘度可显著改变区域分布。0.25%的XG涂层促进了更深的后鼻腔易位,而1%的XG涂层增强了中鼻甲区域的保留。结论:这些发现强调了在体外鼻模型中加入合成粘液的重要性,以提高生理相关性,并为优化鼻内给药技术提供见解。
Quantitative Investigation of Synthetic Mucus Effects on Spray Deposition in a 3D-Printed SLA Nasal Cavity Model.
Purpose: To quantify the deposition distribution of intranasally administered sprays in an anatomically accurate 3D-printed nasal model under varying conditions.
Methods: A multipiece nasal cast was used to assess deposition under three head positions (upright, 22.5° backward tilt, and 45° backward tilt) and two airflow conditions (no flow and gentle sniff). Synthetic mucus coatings were prepared using saline-based xanthan gum (XG) solutions with two different XG concentrations: 0.25% w/v, representing a healthy state, and 1% w/v, representing a diseased state. Regional doses were quantified using salinity-based measurements for both uncoated and coated nasal casts.
Results: The results demonstrate that synthetic mucus coatings significantly altered intranasal spray dosimetry, promoting broader spreading and deeper translocation compared to dry-wall models. In the middle turbinate region, the highest mean deposition occurred under sniff airflow at a 45° backward tilt with a 1% XG coating (76 ppm), representing a 244% increase over the dry condition (22 ppm). For the posterior nasal cavity, the most effective mean deposition was achieved at a 22.5° backward tilt with sniff airflow and a 0.25% XG coating (63 ppm vs. 0 ppm dry). The mucus viscosity can significantly alter regional distribution. A 0.25% XG coating facilitated deeper translocation to the posterior nasal cavity, while 1% XG enhanced retention in the middle turbinate region.
Conclusions: These findings highlight the importance of incorporating synthetic mucus in in vitro nasal models to improve physiological relevance and provide insights for optimizing intranasal drug delivery techniques.
期刊介绍:
Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to:
-(pre)formulation engineering and processing-
computational biopharmaceutics-
drug delivery and targeting-
molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)-
pharmacokinetics, pharmacodynamics and pharmacogenetics.
Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.