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载三氯醋酸曲安奈德 PLGA-壳聚糖纳米粒经眼部给药治疗眼内炎症。

Nanodelivery of triamcinolone acetonide with PLGA-chitosan nanoparticles for the treatment of ocular inflammation.

机构信息

Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Artif Cells Nanomed Biotechnol. 2021 Dec;49(1):308-316. doi: 10.1080/21691401.2021.1895184.

Abstract

Triamcinolone acetonide (TA) is widely indicated in the treatment of several ocular disorders, but the free drug suspension limits its clinical benefits and commercial compositions cause adverse ocular effects. In this study, TA was formulated in poly(d,l-lactide-co-glycolide) (PLGA)-chitosan (PLC) nanoparticles (NPs) for the treatment of ocular inflammatory diseases. TA-loaded PLC NPs exhibited excellent anti-inflammatory activity against human corneal epithelial (HCE) cells and significantly reduced the secretion of interleukin (IL)-6 in tumour necrosis factor (TNF)-α activated cells. In a rabbit model, TA-loaded PLC NPs did not show any typical clinical signs of eye inflammation and significantly alleviated inflammatory signs, compared with free TA suspension, at 24 h after a single dose. TA-loaded PLC NPs exhibited a greater aqueous humour transparency (%AHT), compared with that of normal saline (NS) or free TA suspension, indicating reduction in anterior chamber fogginess. Pharmacokinetic analysis of rabbit eyes revealed that TA-loaded PLC NPs peaked at 6 h. Substantial concentrations of TA were observed until 24 h, indicating the superiority of this PLC-based nanocarrier system. Overall, PLC-based NP formulations offer a new approach for the treatment of ocular inflammatory diseases.

摘要

曲安奈德(TA)广泛应用于多种眼部疾病的治疗,但游离药物混悬剂限制了其临床应用,且商业制剂会引起眼部不良反应。本研究将 TA 制成聚(DL-丙交酯-共-乙交酯)(PLGA)-壳聚糖(PLC)纳米粒(NPs),用于治疗眼部炎症性疾病。TA 负载的 PLC NPs 对人角膜上皮(HCE)细胞表现出优异的抗炎活性,并显著降低 TNF-α 激活细胞中白细胞介素(IL)-6 的分泌。在兔模型中,与游离 TA 混悬剂相比,单剂量给药 24 h 后,TA 负载的 PLC NPs 未显示任何眼部炎症的典型临床迹象,明显缓解了炎症迹象。与生理盐水(NS)或游离 TA 混悬剂相比,TA 负载的 PLC NPs 具有更高的房水透明度(%AHT),表明前房混浊减轻。兔眼的药代动力学分析显示,TA 负载的 PLC NPs 在 6 h 时达到峰值。直到 24 h 仍观察到大量 TA,表明该基于 PLC 的纳米载体系统具有优越性。总之,基于 PLC 的 NPs 制剂为眼部炎症性疾病的治疗提供了一种新方法。

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