{"title":"脉冲超声通过人体巩膜介导的药物传递增强。","authors":"Shuqi You, Suqian Wu, Shicheng Yang, Zhenyang Zhao, Wei Chen, Xiangwu Chen, Huan Wang, Qing Xia, Jiawei Xiong, Hongsheng Zhou, Xiaofen Mo","doi":"10.1167/tvst.14.1.7","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to characterize whether pulsed ultrasound (PUS) affects transscleral drug delivery.</p><p><strong>Methods: </strong>Fluorescein sodium (NaF, 376 Da) and fluorescein isothiocyanate-conjugated dextran 40 (FD-40, 40 kDa) were used as model drugs. Human sclera grafts were placed in modified Franz diffusion cells and were treated by PUS (1 megahertz [MHz], 0.71 W/cm2, duty cycle 30%, application time 5 minutes) once or repeatedly under various conditions to assess permeation enhancement and reservoir effect. The safety of PUS application was assessed on human sclera grafts ex vivo and rabbit eyes in vivo by histology and temperature measurements.</p><p><strong>Results: </strong>Single PUS application yielded a significant increase in FD-40 permeation (P < 0.05). Repeated PUS applications led to a further enhancement in FD-40 permeation and also significantly promoted NaF permeation (more than 8.51-fold, P < 0.05). The human scleral permeability was temporarily modified by PUS, as evidenced by the increased scleral permeability during PUS application and the unchanged permeability coefficients at steady state. The reservoir effect of human sclera was also enhanced by PUS application. Cavitation was detected under PUS. A minor increase in graft temperature rise (<1°C) and no ocular damage was caused by PUS.</p><p><strong>Conclusions: </strong>PUS is an efficient and safe method to enhance model drugs to transport across human sclera by increasing the scleral permeability transiently and improving the reservoir effect. The enhancement was correlated with the molecule size and further promoted by the repeated PUS application.</p><p><strong>Translational relevance: </strong>Our study provides proof of concept for using PUS to enhance drug delivery to the posterior eye segment.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 1","pages":"7"},"PeriodicalIF":2.6000,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734544/pdf/","citationCount":"0","resultStr":"{\"title\":\"Pulsed Ultrasound-Mediated Drug Delivery Enhancement Through Human Sclera.\",\"authors\":\"Shuqi You, Suqian Wu, Shicheng Yang, Zhenyang Zhao, Wei Chen, Xiangwu Chen, Huan Wang, Qing Xia, Jiawei Xiong, Hongsheng Zhou, Xiaofen Mo\",\"doi\":\"10.1167/tvst.14.1.7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>The purpose of this study was to characterize whether pulsed ultrasound (PUS) affects transscleral drug delivery.</p><p><strong>Methods: </strong>Fluorescein sodium (NaF, 376 Da) and fluorescein isothiocyanate-conjugated dextran 40 (FD-40, 40 kDa) were used as model drugs. Human sclera grafts were placed in modified Franz diffusion cells and were treated by PUS (1 megahertz [MHz], 0.71 W/cm2, duty cycle 30%, application time 5 minutes) once or repeatedly under various conditions to assess permeation enhancement and reservoir effect. The safety of PUS application was assessed on human sclera grafts ex vivo and rabbit eyes in vivo by histology and temperature measurements.</p><p><strong>Results: </strong>Single PUS application yielded a significant increase in FD-40 permeation (P < 0.05). Repeated PUS applications led to a further enhancement in FD-40 permeation and also significantly promoted NaF permeation (more than 8.51-fold, P < 0.05). The human scleral permeability was temporarily modified by PUS, as evidenced by the increased scleral permeability during PUS application and the unchanged permeability coefficients at steady state. The reservoir effect of human sclera was also enhanced by PUS application. Cavitation was detected under PUS. A minor increase in graft temperature rise (<1°C) and no ocular damage was caused by PUS.</p><p><strong>Conclusions: </strong>PUS is an efficient and safe method to enhance model drugs to transport across human sclera by increasing the scleral permeability transiently and improving the reservoir effect. The enhancement was correlated with the molecule size and further promoted by the repeated PUS application.</p><p><strong>Translational relevance: </strong>Our study provides proof of concept for using PUS to enhance drug delivery to the posterior eye segment.</p>\",\"PeriodicalId\":23322,\"journal\":{\"name\":\"Translational Vision Science & Technology\",\"volume\":\"14 1\",\"pages\":\"7\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-01-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734544/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational Vision Science & Technology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1167/tvst.14.1.7\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"OPHTHALMOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Vision Science & Technology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1167/tvst.14.1.7","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
Pulsed Ultrasound-Mediated Drug Delivery Enhancement Through Human Sclera.
Purpose: The purpose of this study was to characterize whether pulsed ultrasound (PUS) affects transscleral drug delivery.
Methods: Fluorescein sodium (NaF, 376 Da) and fluorescein isothiocyanate-conjugated dextran 40 (FD-40, 40 kDa) were used as model drugs. Human sclera grafts were placed in modified Franz diffusion cells and were treated by PUS (1 megahertz [MHz], 0.71 W/cm2, duty cycle 30%, application time 5 minutes) once or repeatedly under various conditions to assess permeation enhancement and reservoir effect. The safety of PUS application was assessed on human sclera grafts ex vivo and rabbit eyes in vivo by histology and temperature measurements.
Results: Single PUS application yielded a significant increase in FD-40 permeation (P < 0.05). Repeated PUS applications led to a further enhancement in FD-40 permeation and also significantly promoted NaF permeation (more than 8.51-fold, P < 0.05). The human scleral permeability was temporarily modified by PUS, as evidenced by the increased scleral permeability during PUS application and the unchanged permeability coefficients at steady state. The reservoir effect of human sclera was also enhanced by PUS application. Cavitation was detected under PUS. A minor increase in graft temperature rise (<1°C) and no ocular damage was caused by PUS.
Conclusions: PUS is an efficient and safe method to enhance model drugs to transport across human sclera by increasing the scleral permeability transiently and improving the reservoir effect. The enhancement was correlated with the molecule size and further promoted by the repeated PUS application.
Translational relevance: Our study provides proof of concept for using PUS to enhance drug delivery to the posterior eye segment.
期刊介绍:
Translational Vision Science & Technology (TVST), an official journal of the Association for Research in Vision and Ophthalmology (ARVO), an international organization whose purpose is to advance research worldwide into understanding the visual system and preventing, treating and curing its disorders, is an online, open access, peer-reviewed journal emphasizing multidisciplinary research that bridges the gap between basic research and clinical care. A highly qualified and diverse group of Associate Editors and Editorial Board Members is led by Editor-in-Chief Marco Zarbin, MD, PhD, FARVO.
The journal covers a broad spectrum of work, including but not limited to:
Applications of stem cell technology for regenerative medicine,
Development of new animal models of human diseases,
Tissue bioengineering,
Chemical engineering to improve virus-based gene delivery,
Nanotechnology for drug delivery,
Design and synthesis of artificial extracellular matrices,
Development of a true microsurgical operating environment,
Refining data analysis algorithms to improve in vivo imaging technology,
Results of Phase 1 clinical trials,
Reverse translational ("bedside to bench") research.
TVST seeks manuscripts from scientists and clinicians with diverse backgrounds ranging from basic chemistry to ophthalmic surgery that will advance or change the way we understand and/or treat vision-threatening diseases. TVST encourages the use of color, multimedia, hyperlinks, program code and other digital enhancements.