School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Department of Ophthalmology, Emory University, Atlanta, GA, USA.
Transl Vis Sci Technol. 2023 Mar 1;12(3):31. doi: 10.1167/tvst.12.3.31.
Methods of injection into the suprachoroidal space (SCS) have been developed for larger animals and humans, but reliable administration to the SCS of rodents remains challenging given their substantially smaller eyes. Here, we developed microneedle (MN)-based injectors for SCS delivery in rats and guinea pigs.
We optimized key design features, including MN size and tip characteristics, MN hub design, and eye stabilization, to maximize injection reliability. Performance of the injection technique was characterized in rats (n = 13) and guinea pigs (n = 3) in vivo using fundoscopy and histological examinations to validate targeted SCS delivery.
To enable SCS injection across the thin rodent sclera, the injector featured an ultrasmall, hollow MN measuring 160 µm in length for rats and 260 µm for guinea pigs. To control MN interaction with the scleral surface, we incorporated a three-dimensional (3D) printed needle hub to restrict scleral deformation at the injection site. A MN tip outer diameter of 110 µm and bevel angle of 55° optimized insertion without leakage. Additionally, a 3D printed probe was used to secure the eye by applying gentle vacuum. Injection by this technique took 1 minute to perform, was conducted without an operating microscope, and yielded a 100% success rate (19 of 19) of SCS delivery determined by fundoscopy and histology. A 7-day safety study revealed no notable adverse ocular effects.
We conclude that this simple, targeted, and minimally invasive injection technique can enable SCS injection in rats and guinea pigs.
This MN injector for rats and guinea pigs will expand and expedite preclinical investigations involving SCS delivery.
已经开发出用于巩膜上腔（SCS）注射的方法，这些方法适用于较大的动物和人类，但由于啮齿动物的眼睛小得多，可靠地将药物递送至 SCS 仍然具有挑战性。在这里，我们开发了基于微针（MN）的注射器，用于在大鼠和豚鼠中进行 SCS 给药。
我们优化了关键设计特征，包括 MN 的大小和尖端特征、MN 管座设计以及眼睛稳定，以最大限度地提高注射的可靠性。通过眼底镜检查和组织学检查在大鼠（n=13）和豚鼠（n=3）体内对注射技术的性能进行了表征，以验证靶向 SCS 给药。
为了能够在薄的啮齿动物巩膜上进行 SCS 注射，注射器采用了一种超小的空心 MN，其长度为 160 µm，适用于大鼠，260 µm 适用于豚鼠。为了控制 MN 与巩膜表面的相互作用，我们采用了 3D 打印的针座，以限制注射部位的巩膜变形。MN 尖端的外径为 110 µm，斜角为 55°，优化了插入而不会发生泄漏。此外，使用 3D 打印探头通过施加轻微的真空来固定眼睛。通过该技术进行注射需要 1 分钟的时间，无需手术显微镜即可进行，并且眼底镜和组织学检查确定 19 次中有 19 次（100%）成功进行了 SCS 给药。7 天的安全性研究表明，没有明显的眼部不良影响。
我们得出结论，这种简单、靶向和微创的注射技术可以在大鼠和豚鼠中进行 SCS 注射。
张可馨
