脉冲超声通过人体巩膜介导的药物传递增强。

IF 2.6 3区 医学 Q2 OPHTHALMOLOGY
Shuqi You, Suqian Wu, Shicheng Yang, Zhenyang Zhao, Wei Chen, Xiangwu Chen, Huan Wang, Qing Xia, Jiawei Xiong, Hongsheng Zhou, Xiaofen Mo
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引用次数: 0

摘要

目的:本研究的目的是表征脉冲超声(PUS)是否影响经巩膜给药。方法:以荧光素钠(NaF, 376 Da)和荧光素异硫氰酸酯缀合葡聚糖40 (FD-40, 40 kDa)为模型药物。将人巩膜移植物置于改良的Franz扩散细胞中,在不同条件下用1兆赫(MHz), 0.71 W/cm2,占空比30%,施用时间5分钟的PUS处理一次或多次,评估渗透增强和储层效应。通过组织和温度测量评估体外人巩膜移植和兔眼活体应用脓液的安全性。结果:单次应用脓液可显著增加FD-40的通透性(P)。结论:脓液可瞬间增加巩膜通透性,提高贮药库效应,是一种有效、安全的增强模型药物跨巩膜转运的方法。这种增强与分子大小有关,并因反复使用PUS而进一步增强。翻译相关性:我们的研究证明了使用脓液增强后眼段药物输送的概念。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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来源期刊
Translational Vision Science & Technology
Translational Vision Science & Technology Engineering-Biomedical Engineering
CiteScore
5.70
自引率
3.30%
发文量
346
审稿时长
25 weeks
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.
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