验证基于透明质酸-琼脂的水凝胶作为玻璃体模拟物，用于体外药物和颗粒迁移评估。

Validation of hyaluronic acid-agar-based hydrogels as vitreous humor mimetics for in vitro drug and particle migration evaluations.

机构信息

Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand; School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.

Center for Nanomedicine, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA.

出版信息

Eur J Pharm Biopharm. 2020 Mar;148:118-125. doi: 10.1016/j.ejpb.2020.01.008. Epub 2020 Jan 22.

DOI:10.1016/j.ejpb.2020.01.008

PMID:31981693

Abstract

Artificial vitreous humor holds immense potential for use in in vitro intravitreal drug delivery assays. In this study, we investigated rheological properties and drug or nanoparticle migration in hyaluronic acid (HA) - agar based hydrogels and compared these characteristics with bovine vitreous humor. Gel compositions identified in literature containing HA (0.7-5.0 mg/ml) and agar (0.95-4.0 mg/ml) were classified as either high (VH), medium (VM) or low (VL) polymer load. Viscoelastic behavior was evaluated using oscillatory rheology, and migration of differently sized and charged polystyrene nanoparticles (NPs) through the different gels was determined via multiple particle tracking. Comparable rheological behaviour was observed between VL and bovine vitreous. Tracking evaluations revealed that increasing particle size and gel viscosity slowed NP migration. Additionally, 100 nm anionic NPs migrated slower than neutral NPs in VL and VM, while cationic NPs were immobile in all gels. Finally, distribution and clearance of sodium fluorescein was used to model drug mobility through the gels using a custom-built eye model. Flow and angular movement only influenced drug migration in VL and VM, but not VH. Finally, VL and VM demonstrated to have the most similar sodium fluorescein clearance to that of bovine vitreous humor. Together, these evaluations demonstrate that low viscosity HA-agar gels can be used to approximate nanoparticle and drug migration through biological vitreous humor.

摘要

人工玻璃体在体外玻璃体内药物输送测定中具有巨大的应用潜力。在这项研究中，我们研究了基于透明质酸（HA）-琼脂的水凝胶的流变特性和药物或纳米颗粒的迁移，并将这些特性与牛玻璃体进行了比较。文献中确定的含有 HA（0.7-5.0mg/ml）和琼脂（0.95-4.0mg/ml）的凝胶组成被归类为高（VH）、中（VM）或低（VL）聚合物负载。使用振荡流变学评估粘弹性行为，并通过多颗粒跟踪法确定不同大小和带电的聚苯乙烯纳米颗粒（NPs）在不同凝胶中的迁移情况。VL 和牛玻璃体之间观察到类似的流变行为。跟踪评估表明，增加颗粒大小和凝胶粘度会减缓 NP 迁移。此外，100nm 阴离子 NPs 在 VL 和 VM 中迁移速度比中性 NPs 慢，而阳离子 NPs 在所有凝胶中均不移动。最后，使用定制的眼睛模型，通过将荧光素钠的分布和清除来模拟药物通过凝胶的迁移。仅在 VL 和 VM 中，流动和角运动影响药物迁移，而在 VH 中则不影响。最后，VL 和 VM 表现出与牛玻璃体最相似的荧光素钠清除率。总之，这些评估表明，低粘度 HA-琼脂凝胶可用于模拟纳米颗粒和药物通过生物玻璃体的迁移。