Cardiff University, School of Optometry & Vision Sciences, Cardiff, UK.
Cardiff University, School of Dentistry, Cardiff, UK.
J Control Release. 2024 Aug;372:209-220. doi: 10.1016/j.jconrel.2024.06.029. Epub 2024 Jun 22.
Retinal diseases are the leading cause of blindness, resulting in irreversible degeneration and death of retinal neurons. One such cell type, the retinal ganglion cell (RGC), is responsible for connecting the retina to the rest of the brain through its axons that make up the optic nerve and is the primary cell lost in glaucoma and traumatic optic neuropathy. To date, different therapeutic strategies have been investigated to protect RGCs from death and preserve vision, yet currently available strategies are restricted to treating neuron loss by reducing intraocular pressure. A major barrier identified by these studies is drug delivery to RGCs, which is in large part due to drug stability, short duration time at target, low delivery efficiency, and undesired off-target effects. Therefore, a delivery system to deal with these problems is needed to ensure maximum benefit from the candidate therapeutic material. Extracellular vesicles (EV), nanocarriers released by all cells, are lipid membranes encapsulating RNAs, proteins, and lipids. As they naturally shuttle these encapsulated compounds between cells for communicative purposes, they may be exploitable and offer opportunities to overcome hurdles in retinal drug delivery, including drug stability, drug molecular weight, barriers in the retina, and drug adverse effects. Here, we summarize the potential of an EV drug delivery system, discussing their superiorities and potential application to target RGCs.
视网膜疾病是导致失明的主要原因,导致视网膜神经元的不可逆转的退化和死亡。其中一种细胞类型,视网膜神经节细胞(RGC),通过其构成视神经的轴突将视网膜与大脑的其余部分连接起来,是青光眼和创伤性视神经病变中主要丢失的细胞。迄今为止,已经研究了不同的治疗策略来保护 RGC 免受死亡并保持视力,但目前可用的策略仅限于通过降低眼内压来治疗神经元损失。这些研究确定的一个主要障碍是将药物递送到 RGC 中,这在很大程度上是由于药物稳定性、在靶标处的短持续时间、低递药效率和不理想的脱靶效应。因此,需要一种输送系统来解决这些问题,以确保从候选治疗材料中获得最大益处。细胞外囊泡(EV)是所有细胞释放的纳米载体,是包裹 RNA、蛋白质和脂质的脂质膜。由于它们自然地将这些包裹的化合物在细胞之间穿梭用于通讯目的,因此它们可能是可利用的,并提供了克服视网膜药物输送中的障碍的机会,包括药物稳定性、药物分子量、视网膜中的障碍和药物不良反应。在这里,我们总结了 EV 药物输送系统的潜力,讨论了它们的优势和潜在的应用,以靶向 RGC。