Matteo Tollemeto , Lasse H.E. Thamdrup , Nikos S. Hatzakis , Claus-Michael Lehr , Jan van Hest , Anja Boisen
{"title":"纳米颗粒穿过粘膜屏障:用单颗粒跟踪区分粘膜粘附和粘膜穿透","authors":"Matteo Tollemeto , Lasse H.E. Thamdrup , Nikos S. Hatzakis , Claus-Michael Lehr , Jan van Hest , Anja Boisen","doi":"10.1016/j.jconrel.2025.114268","DOIUrl":null,"url":null,"abstract":"<div><div>Mucus is a viscoelastic, selectively permeable barrier that protects epithelial surfaces throughout the body. Its complex structure presents a major challenge for nanoparticle-based drug delivery, requiring a balance between mucoadhesion, to prolong residence time, and mucopenetration, to access underlying tissues. These processes vary by anatomical site due to differences in mucus turnover and composition.</div><div>Current methods often fail to clearly distinguish between mucoadhesion and mucopenetration. Here, we highlight single-particle tracking (SPT) as a powerful approach to address this gap. By capturing the trajectories of individual nanoparticles in mucus, SPT offers high-resolution insight into their diffusion behavior and interaction dynamics. Notably, particle behavior observed in <em>ex vivo</em> mucus has shown good correlation with <em>in vivo</em> outcomes, making SPT a promising tool for translational research.</div><div>Despite its advantages, SPT remains underutilized in mucosal drug delivery, largely due to a lack of standardized protocols and benchmark materials. We advocate for the development of a nanoparticle test set with well-defined surface properties (<em>e.g.</em>, charge, hydrophobicity) and the routine reporting of key parameters such as diffusion coefficients and mean squared displacement. These steps are essential to improve reproducibility, support cross-study comparisons, and accelerate progress in mucosal nanomedicine.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"388 ","pages":"Article 114268"},"PeriodicalIF":11.5000,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Nanoparticles across mucosal barriers: Differentiating mucoadhesion from mucopenetration using single particle tracking\",\"authors\":\"Matteo Tollemeto , Lasse H.E. Thamdrup , Nikos S. Hatzakis , Claus-Michael Lehr , Jan van Hest , Anja Boisen\",\"doi\":\"10.1016/j.jconrel.2025.114268\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Mucus is a viscoelastic, selectively permeable barrier that protects epithelial surfaces throughout the body. Its complex structure presents a major challenge for nanoparticle-based drug delivery, requiring a balance between mucoadhesion, to prolong residence time, and mucopenetration, to access underlying tissues. These processes vary by anatomical site due to differences in mucus turnover and composition.</div><div>Current methods often fail to clearly distinguish between mucoadhesion and mucopenetration. Here, we highlight single-particle tracking (SPT) as a powerful approach to address this gap. By capturing the trajectories of individual nanoparticles in mucus, SPT offers high-resolution insight into their diffusion behavior and interaction dynamics. Notably, particle behavior observed in <em>ex vivo</em> mucus has shown good correlation with <em>in vivo</em> outcomes, making SPT a promising tool for translational research.</div><div>Despite its advantages, SPT remains underutilized in mucosal drug delivery, largely due to a lack of standardized protocols and benchmark materials. We advocate for the development of a nanoparticle test set with well-defined surface properties (<em>e.g.</em>, charge, hydrophobicity) and the routine reporting of key parameters such as diffusion coefficients and mean squared displacement. These steps are essential to improve reproducibility, support cross-study comparisons, and accelerate progress in mucosal nanomedicine.</div></div>\",\"PeriodicalId\":15450,\"journal\":{\"name\":\"Journal of Controlled Release\",\"volume\":\"388 \",\"pages\":\"Article 114268\"},\"PeriodicalIF\":11.5000,\"publicationDate\":\"2025-09-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Controlled Release\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0168365925008806\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Controlled Release","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0168365925008806","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Nanoparticles across mucosal barriers: Differentiating mucoadhesion from mucopenetration using single particle tracking
Mucus is a viscoelastic, selectively permeable barrier that protects epithelial surfaces throughout the body. Its complex structure presents a major challenge for nanoparticle-based drug delivery, requiring a balance between mucoadhesion, to prolong residence time, and mucopenetration, to access underlying tissues. These processes vary by anatomical site due to differences in mucus turnover and composition.
Current methods often fail to clearly distinguish between mucoadhesion and mucopenetration. Here, we highlight single-particle tracking (SPT) as a powerful approach to address this gap. By capturing the trajectories of individual nanoparticles in mucus, SPT offers high-resolution insight into their diffusion behavior and interaction dynamics. Notably, particle behavior observed in ex vivo mucus has shown good correlation with in vivo outcomes, making SPT a promising tool for translational research.
Despite its advantages, SPT remains underutilized in mucosal drug delivery, largely due to a lack of standardized protocols and benchmark materials. We advocate for the development of a nanoparticle test set with well-defined surface properties (e.g., charge, hydrophobicity) and the routine reporting of key parameters such as diffusion coefficients and mean squared displacement. These steps are essential to improve reproducibility, support cross-study comparisons, and accelerate progress in mucosal nanomedicine.
期刊介绍:
The Journal of Controlled Release (JCR) proudly serves as the Official Journal of the Controlled Release Society and the Japan Society of Drug Delivery System.
Dedicated to the broad field of delivery science and technology, JCR publishes high-quality research articles covering drug delivery systems and all facets of formulations. This includes the physicochemical and biological properties of drugs, design and characterization of dosage forms, release mechanisms, in vivo testing, and formulation research and development across pharmaceutical, diagnostic, agricultural, environmental, cosmetic, and food industries.
Priority is given to manuscripts that contribute to the fundamental understanding of principles or demonstrate the advantages of novel technologies in terms of safety and efficacy over current clinical standards. JCR strives to be a leading platform for advancements in delivery science and technology.