Sapino Simona, Chindamo Giulia, Peira Elena, Chirio Daniela, Foglietta Federica, Serpe Loredana, Vizio Barbara, Gallarate Marina
Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy.
Department of Medical Sciences, University of Turin, Via Genova 3, 10126 Turin, Italy.
Pharmaceutics. 2023 Oct 16;15(10):2472. doi: 10.3390/pharmaceutics15102472.
Repeated intravitreal (IVT) injections in the treatment of retinal diseases can lead to severe complications. Developing innovative drug delivery systems for IVT administration is crucial to prevent adverse reactions, but requires extensive investigation including the use of different preclinical models (in vitro, ex vivo and in vivo). Our previous work described an in vitro tricompartmental ocular flow cell (TOFC) simulating the anterior and posterior cavities of the human eye. Based on promising preliminary results, in this study, a collagen scaffold enriched with human retinal pigmented epithelial cells (ARPE-19) was developed and introduced into the TOFC to partially mimic the human retina. Cells were cultured under dynamic flow conditions to emulate the posterior segment of the human eye. Bevacizumab was then injected into the central compartment of the TOFC to treat ARPE-19 cells and assess its effects. The results showed an absence of cytotoxic activity and a significant reduction in VEGF fluorescent signal, underscoring the potential of this in vitro model as a platform for researching new ophthalmic formulations addressing the posterior eye segment, eventually decreasing the need for animal testing.
反复玻璃体内(IVT)注射用于治疗视网膜疾病可能会导致严重并发症。开发用于IVT给药的创新药物递送系统对于预防不良反应至关重要,但需要进行广泛研究,包括使用不同的临床前模型(体外、离体和体内)。我们之前的工作描述了一种模拟人眼前房和后房的体外三室眼流动池(TOFC)。基于有前景的初步结果,在本研究中,开发了一种富含人视网膜色素上皮细胞(ARPE-19)的胶原支架,并将其引入TOFC以部分模拟人视网膜。细胞在动态流动条件下培养以模拟人眼后段。然后将贝伐单抗注入TOFC的中央隔室以处理ARPE-19细胞并评估其效果。结果显示没有细胞毒性活性,并且VEGF荧光信号显著降低,这突出了这种体外模型作为研究针对眼后段的新眼科制剂的平台的潜力,最终减少了动物试验的需求。