Investigating the structural integrity of nanocarriers in vivo is vital for exploring the fate of nanocarriers from ocular surface to the posterior segment of the eye. Most of the published studies adopted the structural integrity ratio of nanocarriers to determine the fate of them, which lacked scientific support. In this study, two methods were used to explore the factors which affected the structural integrity of liposomes. A new method with the standard curve of FRET fluorescence intensity and carbocyanine 7 (Cy7) content was drawn for the first time. Secondly, we used the traditional method of drawing the standard curve of FRET fluorescence efficiency and structural integrity ratios. The results showed that liposomes with particle size about 120 nm, positively charged, polyethyleneglycol5000 (PEG5000) and glycine sarcosine (GS) modified had the highest Cy7 content in rabbit tissues. When the dosage of Cy7 was 25 μg, at 60 min, the content of Cy7 in intact liposomes and the structural integrity ratio of liposomes in sclera was 210.5 ± 14.9 ng and 19.8 ± 5.3 %, respectively. Compared with the structural integrity ratio, the Cy7 content in the intact carrier could better estimate the fate of nanocarriers in vivo scientifically. On this basis, the fate of dual-carrier nanocomposites and the inner cyclodextrin complexes in vivo was investigated. The intact cyclodextrin complexes could reach choroid-retina with the protection of outer liposomes. The structural integrity ratios of liposomes were also studied after crossing human conjunctival epithelial cells (HConEpiC) monolayer, but in vitro cellular experiments could not simulate the real situation in vivo. Finally, the tissue distribution of nanocomposites was studied in rabbit eyes. The concentration of dexamethasone (Dex) in choroid-retina was 158 ± 23 ng/g after 3 h, which exhibited better drug delivery ability compared with our previous study. Overall, the present study provides a new scientific method to estimate the structural integrity in vivo, which is beneficial for the rational design of drug delivery systems with more structural integrity in vivo and higher drug delivery efficiency.

中文翻译：

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基于 FRET 的脂质体和 cyclodextrin@liposome 纳米复合材料从眼表到眼后段的命运分析


研究体内纳米载体的结构完整性对于探索纳米载体从眼表到眼后段的命运至关重要。大多数已发表的研究采用纳米载体的结构完整性比率来确定它们的命运，这缺乏科学支持。在本研究中，使用了两种方法来探索影响脂质体结构完整性的因素。首次绘制了 FRET 荧光强度和羰花青 7 （Cy7） 含量标准曲线的新方法。其次，我们采用传统方法绘制 FRET 荧光效率和结构完整性比的标准曲线。结果表明，粒径约为 120 nm、带正电荷、聚乙二醇 5000 （PEG5000） 和甘氨酸肌氨酸 （GS） 修饰的脂质体在兔组织中 Cy7 含量最高。当 Cy7 的用量为 25 μg 时，在 60 min 时，完整脂质体中 Cy7 的含量和巩膜中脂质体的结构完整性比分别为 210.5 ± 14.9 ng 和 19.8 ± 5.3 %。与结构完整性比相比，完整载体中的 Cy7 含量可以更好地科学地估计纳米载体在体内的命运。在此基础上，研究了双载流子纳米复合材料和体内环糊精复合物的命运。完整的环糊精复合物可以在外脂质体的保护下到达脉络膜视网膜。在穿过人结膜上皮细胞 （HConEpiC） 单层后，也研究了脂质体的结构完整性比值，但体外细胞实验无法模拟体内真实情况。最后，研究了纳米复合材料在兔眼中的组织分布。 3 h后脉络膜视网膜中地塞米松（Dex）浓度为158 ± 23 ng/g，与我们之前的研究相比表现出更好的药物递送能力。综上所述，本研究提供了一种新的科学方法来估计体内结构完整性，有利于合理设计具有更多体内结构完整性和更高药物递送效率的药物递送系统。