Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
Eur J Pharm Biopharm. 2017 Oct;119:125-136. doi: 10.1016/j.ejpb.2017.06.009. Epub 2017 Jun 8.
Intravitreal injection is the most common administration route for the treatment of retinal diseases. However, the vitreous and some of the retinal layers themselves act as significant barriers to efficient delivery of drugs administered intravitreally. This study aimed to improve the diffusive mobility of nanoparticles (NPs) in the vitreous and enhance their permeation across the retina after intravitreal injection by application of ultrasound (US). Ex vivo posterior bovine eye cups were used and the vitreous was either left intact or removed gently from the neural retina. Hyaluronic acid coated human serum albumin NPs were administered into the eye cups and continuous US with a frequency of 1MHz, an intensity of 0.5W/cm, and a duration of 30s was applied once or repeatedly via the transscleral route. After pre-determined time points, fluorescence intensities in the vitreous and the retina were analyzed. Short pulses of US significantly improved the diffusive mobility of NPs through the vitreous as well as their penetration across the neural retina into the retinal pigment epithelium and choroid without causing any detectable damage to the ocular tissues. Therefore, transscleral US could be a powerful and safe tool to enhance retinal delivery of intravitreally injected NPs.
玻璃体内注射是治疗视网膜疾病最常用的给药途径。然而，玻璃体和部分视网膜层本身是药物有效递送至玻璃体内的显著障碍。本研究旨在通过应用超声（US）来提高纳米颗粒（NPs）在玻璃体内的扩散迁移能力，并增强其在玻璃体内注射后的穿透视网膜能力。使用离体牛眼杯，玻璃体液要么保持完整，要么从神经视网膜轻轻去除。将透明质酸包覆的人血清白蛋白 NPs 注入眼杯中，并通过经巩膜途径单次或重复施加频率为 1MHz、强度为 0.5W/cm 和持续时间为 30s 的连续 US。在预定的时间点后，分析玻璃体内和视网膜中的荧光强度。短脉冲 US 显著改善了 NPs 通过玻璃体的扩散迁移能力，以及它们穿透神经视网膜进入视网膜色素上皮和脉络膜的能力，而不会对眼组织造成任何可检测的损伤。因此，经巩膜 US 可能是增强玻璃体内注射 NPs 视网膜递药的强大且安全的工具。
