This study employed superficial ultrasound exposure of good ocular safety and a drug-loaded hydrogel of long residence time to enable transscleral delivery. First, we designed an acoustic adaptor to limit the ultrasound exposure depth to 1.59 mm to protect the posterior eye segments. Then, we optimized the alginate/polyacrylamide ratio (3:7) of a dual-crosslinked hydrogel to enable ultrasound-triggered release of model drug (70-kDa fluorescein isothiocyanate-conjugated dextran). Using fluorescence imaging to quantify the drug release, we showed that the developed method resulted in enhanced transscleral delivery in both ex vivo porcine scleras (2.6-fold) and in vivo rabbit scleras (2.2-fold). We also demonstrated that the method increased the drug penetration depth to the whole thickness of the sclera. In particular, the drug release efficiency increased with increasing ultrasound exposure time (1 and 3 min) and intensity (8, 19, 36, and 61 mW/cm²). Using scanning electron microscopy, we revealed that ultrasound exposure resulted in rougher surfaces and microscale rupture of the hydrogel. Moreover, Masson staining of scleral slices showed that the integrity of the top scleral fibers was disturbed by ultrasound exposure, and this disturbance recovered 3 days later. Our work demonstrates that the developed method holds great potential for mediating ocular drug delivery.

这项研究采用了具有良好眼部安全性的表面超声暴露和具有长停留时间的载药水凝胶来实现经巩膜递送。首先，我们设计了一个声学适配器，将超声暴露深度限制为 1.59 mm，以保护眼后段。然后，我们优化了双交联水凝胶的藻酸盐/聚丙烯酰胺比例（3:7），以实现模型药物（70-kDa 荧光素异硫氰酸酯缀合葡聚糖）的超声触发释放。使用荧光成像来量化药物释放，我们表明所开发的方法可增强离体猪巩膜（2.6 倍）和体内兔巩膜（2.2 倍）的经巩膜递送。我们还证明该方法将药物渗透深度增加到巩膜的整个厚度。特别是，药物释放效率随着超声暴露时间（1和3分钟）和强度（8、19、36和61 mW/cm ² ）的增加而增加。使用扫描电子显微镜，我们发现超声波暴露导致水凝胶表面更粗糙和微尺度破裂。此外，巩膜切片的马森染色显示，顶部巩膜纤维的完整性受到超声波照射的干扰，并且这种干扰在3天后恢复。我们的工作表明，所开发的方法在介导眼部药物输送方面具有巨大的潜力。