PDF(Pubmed)
Abstract：
Nanomedicine has the potential to increase the biostability of drugs to treat retinal diseases, improving their performance and decreasing the required number of intravitreal injections. However, accurate pharmacokinetic studies of these nanoparticle-drug conjugates, nanoparticle motion across the vitreous humour and interaction with the retinal cell layers still need to be investigated. Existing nanoparticle tracking techniques require fluorescent labels, which can impact cytotoxicity, nanoparticles\' motion, protein interactions, and cell internalization. In this study, a real-time label-free tracking technology, for single nanoparticles in an optical microscope based on the optical phenomena of caustics, was used to characterise the diffusion of nanoparticles in agar-hyaluronic acid hydrogels, previously validated as vitreous humour substitutes for in vitro models. The results demonstrated that the diffusion of nanoparticles through these hydrogels was heterogeneous, and that nanoparticle size had an important role in nanoparticle distribution across and within in vitro vitreous substitutes. These findings suggest that nanoparticle diameter is a critical parameter for designing novel therapeutics for retinal diseases. Moreover, nanoparticle charge did not affect nanoparticle diffusion or distribution in these synthetic hydrogels. The use of caustics in optical microscopy has been demonstrated to be a reproducible, inexpensive technique for screening novel therapeutics in eye in vitro models.
摘要：
纳米医学有可能增加治疗视网膜疾病的药物的生物稳定性，改善其性能并减少所需的玻璃体内注射次数。然而,这些纳米颗粒-药物偶联物的准确药代动力学研究，纳米颗粒在玻璃体液中的运动以及与视网膜细胞层的相互作用仍需要研究。现有的纳米粒子跟踪技术需要荧光标记，会影响细胞毒性，纳米粒子的运动，蛋白质相互作用，和细胞内化。在这项研究中,实时无标签跟踪技术，对于基于焦散光学现象的光学显微镜中的单个纳米颗粒，用于表征纳米颗粒在琼脂-透明质酸水凝胶中的扩散，先前验证为体外模型的玻璃体液替代品。结果表明，纳米粒子通过这些水凝胶的扩散是异质的，纳米粒子的大小对纳米粒子在体外玻璃体替代品中的分布具有重要作用。这些发现表明纳米颗粒直径是设计用于视网膜疾病的新疗法的关键参数。此外，纳米粒子电荷不影响纳米粒子在这些合成水凝胶中的扩散或分布。在光学显微镜中使用焦散已被证明是可重复的，在眼体外模型中筛选新疗法的廉价技术。
