You Shuqi, Wu Suqian, Yang Shicheng, Zhao Zhenyang, Chen Wei, Chen Xiangwu, Wang Huan, Xia Qing, Xiong Jiawei, Zhou Hongsheng, Mo Xiaofen
Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.
Department of Ophthalmology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Transl Vis Sci Technol. 2025 Jan 2;14(1):7. doi: 10.1167/tvst.14.1.7.
The purpose of this study was to characterize whether pulsed ultrasound (PUS) affects transscleral drug delivery.
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.
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.
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.
Our study provides proof of concept for using PUS to enhance drug delivery to the posterior eye segment.
本研究旨在表征脉冲超声（PUS）是否影响经巩膜给药。
使用荧光素钠（NaF，376 Da）和异硫氰酸荧光素偶联的葡聚糖40（FD-40，40 kDa）作为模型药物。将人巩膜移植物置于改良的Franz扩散池中，并在各种条件下一次或多次接受PUS治疗（1兆赫兹[MHz]，0.71 W/cm²，占空比30%，施加时间5分钟），以评估渗透增强和储库效应。通过组织学和温度测量在离体人巩膜移植物和活体兔眼中评估PUS应用的安全性。
单次应用PUS可使FD-40的渗透率显著增加（P < 0.05）。重复应用PUS可进一步增强FD-40的渗透率，并显著促进NaF的渗透（超过8.51倍，P < 0.05）。PUS可暂时改变人巩膜的通透性，PUS应用期间巩膜通透性增加以及稳态时渗透系数不变证明了这一点。PUS应用还增强了人巩膜的储库效应。在PUS作用下检测到空化现象。PUS导致移植物温度略有升高（<1°C），未造成眼部损伤。
PUS是一种有效且安全的方法，可通过短暂增加巩膜通透性和改善储库效应来增强模型药物跨人巩膜的转运。这种增强与分子大小相关，并通过重复应用PUS进一步促进。
我们的研究为使用PUS增强药物向眼后段的递送提供了概念验证。
