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首页> 外文期刊>Investigative ophthalmology & visual science >Extended Intravitreal Rabbit Eye Residence of Nanoparticles Conjugated With Cationic Arginine Peptides for Intraocular Drug Delivery: In Vivo Imaging
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Extended Intravitreal Rabbit Eye Residence of Nanoparticles Conjugated With Cationic Arginine Peptides for Intraocular Drug Delivery: In Vivo Imaging

机译：与阳离子精氨酸肽共轭的眼内药物传递的纳米粒子的玻璃体内兔眼驻留的扩展：体内成像。

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Purpose : Drug delivery by intravitreal injection remains problematic, small agents and macromolecules both clearing rapidly. Typical carriers use microparticles (2 μm), with size-related liabilities, to slow diffusion. We recently described cationic nanoparticles (NP) where conjugated Arg peptides prolonged residence in rat eyes, through ionic interaction with vitreal poly-anions. Here we extended this strategy to in vivo tracking of NP-conjugate (NPC) clearance from rabbit eyes. Relating tsub1/2/sub to zeta potential, and varied dose, we estimated the limits of this charge-based delivery system. Methods : NPC carried covalently attached PEGsub8/sub-2Arg or PEGsub8/sub-3Arg pentapeptides, having known sequences from human eye proteins. Peptides were conjugated (61–64 per NPC); each NP/NPC also carried a cyanine7 tag (1/2/sub of 7 days and 17 days respectively, unconjugated NP tsub1/2/sub was 8/sub-2Arg NPC were compared. The lower doses showed dose-proportional day-10 concentration, and similar clearance. Higher early loss was seen with a 360-μg dose, exceeding rabbit vitreal binding capacity. No inflammation was observed. Conclusions : This type of cationic NPC can safely increase residence tsub1/2/sub in a 1 to 3-week range, with dose 100 μg per mL vitreous. Human drug load may then range from 10 to 100 μg/eye, usefulness depending on individual drug potency and release rate, superimposed on extended intravitreal residence.
机译：目的：玻璃体内注射给药仍然有问题，小分子药物和大分子都可以快速清除。典型的载体使用具有尺寸相关性的微粒（> 2μm）来减缓扩散。我们最近描述了阳离子纳米颗粒（NP），其中结合的Arg肽通过与玻璃体聚阴离子的离子相互作用延长了在大鼠眼中的停留时间。在这里，我们将这种策略扩展到体内跟踪兔眼中NP-共轭物（NPC）的清除率。将t 1/2 与zeta电位相关，并改变剂量，我们估算了这种基于电荷的递送系统的局限性。方法：NPC带有共价结合的PEG 8 -2Arg或PEG 8 -3Arg五肽，其人眼蛋白序列已知。肽被缀合（每个NPC 61-64）;每个NP / NPC还带有一个cyanine7标签（分别为7天和17天的1/2 ，比较未结合的NP t 1/2 为8 Arg 2 NPC）。较低的剂量显示剂量与剂量成正比的第10天浓度，清除率相似;以360μg的剂量观察到较高的早期损失，超过了兔子对玻璃体的结合能力，未观察到炎症反应。 t 1/2 在1至3周的范围内，剂量<100μg/ mL玻璃体，然后人眼载药量可能在10至100μg/眼之间，其有效性取决于各个药物的功效和释放速率，与延长的玻璃体内停留时间叠加。

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