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药物递送银纳米颗粒:苯茚二酮作为抗凝剂的新视角。

Drug-Delivery Silver Nanoparticles: A New Perspective for Phenindione as an Anticoagulant.

作者信息

Nikolova Stoyanka, Milusheva Miglena, Gledacheva Vera, Feizi-Dehnayebi Mehran, Kaynarova Lidia, Georgieva Deyana, Delchev Vassil, Stefanova Iliyana, Tumbarski Yulian, Mihaylova Rositsa, Cherneva Emiliya, Stoencheva Snezhana, Todorova Mina

机构信息

Department of Organic Chemistry, Faculty of Chemistry, University of Plovdiv, 4000 Plovdiv, Bulgaria.

Department of Bioorganic Chemistry, Faculty of Pharmacy, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria.

出版信息

Biomedicines. 2023 Aug 4;11(8):2201. doi: 10.3390/biomedicines11082201.

Abstract

Anticoagulants prevent the blood from developing the coagulation process, which is the primary cause of death in thromboembolic illnesses. Phenindione (PID) is a well-known anticoagulant that is rarely employed because it totally prevents coagulation, which can be a life-threatening complication. The goal of the current study is to synthesize drug-loaded Ag NPs to slow down the coagulation process. Methods: A rapid synthesis and stabilization of silver nanoparticles as drug-delivery systems for phenindione (PID) were applied for the first time. Results: Several methods are used to determine the size of the resulting Ag NPs. Additionally, the drug-release capabilities of Ag NPs were established. Density functional theory (DFT) calculations were performed for the first time to indicate the nature of the interaction between PID and nanostructures. DFT findings supported that galactose-loaded nanostructure could be a proper delivery system for phenindione. The drug-loaded Ag NPs were characterized in vitro for their antimicrobial, cytotoxic, and anticoagulant activities, and ex vivo for spasmolytic activity. The obtained data confirmed the drug-release experiments. Drug-loaded Ag NPs showed that prothrombin time (PT, sec) and activated partial thromboplastin time (APTT, sec) are approximately 1.5 times longer than the normal values, while PID itself stopped coagulation at all. This can make the PID-loaded Ag NPs better therapeutic anticoagulants. PID was compared to PID-loaded Ag NPs in antimicrobial, spasmolytic activity, and cytotoxicity. All the experiments confirmed the drug-release results.

摘要

抗凝剂可防止血液发生凝血过程,而凝血过程是血栓栓塞性疾病的主要死亡原因。苯茚二酮(PID)是一种知名的抗凝剂,但很少使用,因为它会完全阻止凝血,这可能是一种危及生命的并发症。本研究的目的是合成载药银纳米颗粒以减缓凝血过程。方法:首次将银纳米颗粒作为苯茚二酮(PID)的药物递送系统进行快速合成和稳定化处理。结果:使用了几种方法来测定所得银纳米颗粒的尺寸。此外,还确定了银纳米颗粒的药物释放能力。首次进行密度泛函理论(DFT)计算以表明PID与纳米结构之间相互作用的性质。DFT结果支持载半乳糖的纳米结构可能是苯茚二酮的合适递送系统。对载药银纳米颗粒的抗菌、细胞毒性和抗凝活性进行了体外表征,并对其解痉活性进行了离体表征。获得的数据证实了药物释放实验。载药银纳米颗粒显示凝血酶原时间(PT,秒)和活化部分凝血活酶时间(APTT,秒)比正常值长约1.5倍,而PID本身则完全停止了凝血。这可使载PID的银纳米颗粒成为更好的治疗性抗凝剂。将PID与载PID的银纳米颗粒在抗菌、解痉活性和细胞毒性方面进行了比较。所有实验均证实了药物释放结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6750/10452578/4fffe8410d67/biomedicines-11-02201-sch001.jpg

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