DOI: 10.3390/biomedicines11082201 ISSN: 2227-9059

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

Stoyanka Nikolova, Miglena Milusheva, Vera Gledacheva, Mehran Feizi-Dehnayebi, Lidia Kaynarova, Deyana Georgieva, Vassil Delchev, Iliyana Stefanova, Yulian Tumbarski, Rositsa Mihaylova, Emiliya Cherneva, Snezhana Stoencheva, Mina Todorova
  • General Biochemistry, Genetics and Molecular Biology
  • Medicine (miscellaneous)

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.

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