Purpose: The trans-ocular barrier is a key factor limiting the therapeutic efficacy of triamcinolone acetonide. We developed a poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) surface modified respectively with 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD), chitosan oligosaccharide and trehalose. Determination of the drug/nanoparticles interactions, characterization of the nanoparticles, in vivo ocular compatibility tests, comparisons of their corneal permeability and their pharmacokinetics in aqueous humor were carried out.
Methods: All PLGA NPs were prepared by the single emulsion and evaporation method and the drug-nanoparticle interaction was studied. The physiochemical features and in vitro corneal permeability of NPs were characterized while the aqueous humor pharmacokinetics was performed to evaluate in vivo corneal permeability of NPs. Ocular compatibility of NPs was investigated through Draize and histopathological test.
Results: The PLGA NPs with lactide/glycolide ratio of 50:50 and small particle size (molecular weight 10 kDa) achieved optimal drug release and corneal permeability. Surface modification with different oligosaccharides resulted in uniform particle sizes and similar drug-nanoparticle interactions, although 2-HP-β-CD/PLGA NPs showed the highest entrapment efficiency. In vitro evaluation and aqueous humor pharmacokinetics further revealed that 2-HP-β-CD/PLGA NPs had greater trans-ocular permeation and retention compared to chitosan oligosaccharide/PLGA and trehalose/PLGA NPs. No ocular irritation in vivo was detected after applying modified/unmodified PLGA NPs to rabbit’s eyes.
Conclusion: 2-HP-β-CD/PLGA NPs are a promising nanoplatform for localized ocular drug delivery through topical administration.

Keywords: ocular drug delivery, PLGA nanoparticle, ocular barrier, oligosaccharide, local bioavailability, triamcinolone acetonide, eye drop administration


中文翻译：

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PLGA纳米粒子平台用于跨眼屏障增强药物递送：基于寡糖在载体外膜中应用的比较研究

目的：经眼屏障是限制曲安奈德治疗效果的关键因素。我们开发了分别用 2-羟丙基-β-环糊精 (2-HP-β-CD)、壳聚糖寡糖和海藻糖进行表面修饰的聚乳酸-乙醇酸共聚物纳米粒子 (PLGA NPs)。进行了药物/纳米粒子相互作用的测定、纳米粒子的表征、体内眼相容性试验、它们的角膜渗透性和它们在房水中的药代动力学的比较。
方法：所有PLGA NPs均采用单乳液蒸发法制备，并研究了药物-纳米颗粒的相互作用。表征了 NPs 的理化特征和体外角膜通透性，同时进行房水药代动力学以评估 NPs 的体内角膜通透性。通过 Draize 和组织病理学测试研究了 NPs 的眼部相容性。
结果：丙交酯/乙交酯比为 50:50 和小粒径（分子量 10 kDa）的 PLGA NPs 实现了最佳的药物释放和角膜渗透性。尽管 2-HP-β-CD/PLGA NPs 显示出最高的包封效率，但用不同的寡糖进行表面改性会导致粒径均匀且药物-纳米粒子相互作用相似。体外评估和房水药代动力学进一步表明，与壳寡糖/PLGA 和海藻糖/PLGA NPs 相比，2-HP-β-CD/PLGA NPs 具有更大的经眼渗透和保留。将修饰/未修饰的 PLGA NPs 应用于兔子的眼睛后，未检测到体内眼部刺激。
结论： 2-HP-β-CD/PLGA NPs 是一种很有前途的纳米平台，用于通过局部给药进行局部眼部药物递送。

关键词：眼部给药，PLGA纳米颗粒，眼屏障，寡糖，局部生物利用度，曲安奈德，滴眼给药