Amlodipine Ocular Delivery Restores Ferning Patterns and Reduces Intensity of Glycosylated Peak of Carrageenan-Induced Tear Fluid: An InSilico Flexible Docking with IL-Β1

IF 2.8 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Ashirbad Nanda, Rudra Narayan Sahoo, Mahendra Gour, Sandeep Kumar Swain, Debajyoti Das, Amit Kumar Nayak, Subrata Mallick
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Abstract

Background: The tear ferning test can be an easy clinical procedure for the evaluation and characterization of the ocular tear film Objective: The objective of this study was to examine the restoration of tear ferning pattern and reduction of glycosylation peak after amlodipine application in carrageenan-induced conjunctivitis. Methods: At the rabbit’s upper palpebral region, carrageenan was injected for cytokine-mediated conjunctivitis. Ferning pattern and glycosylation of the tear fluid were characterized using various instrumental analyses. The effect of amlodipine was also examined after ocular instillation and flexible docking studies. Results: Optical microscopy showed a disrupted ferning of the tear collected from the inflamed eye. FTIR of the induced tear fluid exhibited peaks within 1000-1200 cm-1 , which might be due to the protein glycosylation, which was absent in the normal tear spectrogram. The glycosylation peak reduced significantly in the tear sample collected from the amlodipine-treated group. Corresponding energy dispersive analysis showed the presence of sulphur, indicating protein leakage from the lacrimal gland in the induced group. The disappearance of sulphur from the treated group indicated its remedial effect. The flexible docking studies revealed a stronger binding mode of amlodipine with Interleukin-1β (IL-1β). The reduction in the intensity of the glycosylated peak and the restoration offering is probably due to suppression of IL-1β. Conclusion: This study may be helpful in obtaining primary information for drug discovery to be effective against IL-1β and proving tear fluid as a novel diagnostic biomarker.
氨氯地平眼部给药恢复蕨类植物模式并降低卡拉胶诱导泪液糖基化峰强度:与IL的硅柔性对接-Β1
目的:本研究旨在探讨氨氯地平应用于卡拉胶性结膜炎后泪蕨形态的恢复和糖基化峰的降低。方法:在家兔上睑区注射卡拉胶治疗细胞因子介导的结膜炎。泪液的蕨类模式和糖基化用各种仪器分析表征。在眼滴注和柔性对接研究后也检查了氨氯地平的效果。结果:光学显微镜显示从发炎的眼睛收集的泪液的蕨类植物被破坏。诱导泪液的FTIR在1000-1200 cm-1范围内显示出峰值,这可能是由于正常泪液谱图中不存在的蛋白质糖基化所致。氨氯地平组泪液中糖基化峰明显降低。相应的能量色散分析显示有硫的存在,提示诱导组泪腺有蛋白质渗漏。治疗组中硫的消失说明其治疗效果。柔性对接研究显示氨氯地平与白细胞介素-1β (IL-1β)的结合模式更强。糖基化峰强度的降低和恢复提供可能是由于IL-1β的抑制。结论:本研究为开发抗IL-1β药物提供了初步信息,并证明泪液是一种新的诊断性生物标志物。
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来源期刊
Current drug delivery
Current drug delivery PHARMACOLOGY & PHARMACY-
CiteScore
5.10
自引率
4.20%
发文量
170
期刊介绍: Current Drug Delivery aims to publish peer-reviewed articles, research articles, short and in-depth reviews, and drug clinical trials studies in the rapidly developing field of drug delivery. Modern drug research aims to build delivery properties of a drug at the design phase, however in many cases this idea cannot be met and the development of delivery systems becomes as important as the development of the drugs themselves. The journal aims to cover the latest outstanding developments in drug and vaccine delivery employing physical, physico-chemical and chemical methods. The drugs include a wide range of bioactive compounds from simple pharmaceuticals to peptides, proteins, nucleotides, nucleosides and sugars. The journal will also report progress in the fields of transport routes and mechanisms including efflux proteins and multi-drug resistance. The journal is essential for all pharmaceutical scientists involved in drug design, development and delivery.
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