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

doi:10.3390/biomedicines11082201

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

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

Authors

Affiliations

¹ Department of Organic Chemistry, Faculty of Chemistry, University of Plovdiv, 4000 Plovdiv, Bulgaria.
² Department of Bioorganic Chemistry, Faculty of Pharmacy, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria.
³ Department of Medical Physics and Biophysics, Faculty of Pharmacy, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria.
⁴ Department of Chemistry, Faculty of Science, University of Sistan and Baluchestan, Zahedan P.O. Box 98135-674, Iran.
⁵ Department of Analytical Chemistry and Computer Chemistry, Faculty of Chemistry, University of Plovdiv, 4000 Plovdiv, Bulgaria.
⁶ Department of Physical Chemistry, Faculty of Chemistry, University of Plovdiv, 4000 Plovdiv, Bulgaria.
⁷ Department of Microbiology, Technological Faculty, University of Food Technologies, 4002 Plovdiv, Bulgaria.
⁸ Laboratory of Experimental Chemotherapy, Department "Pharmacology, Pharmacotherapy and Toxicology", Faculty of Pharmacy, Medical University, 1431 Sofia, Bulgaria.
⁹ Department of Chemistry, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria.
¹⁰ Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., BI 9, 1113 Sofia, Bulgaria.
¹¹ University Hospital "Sveti Georgi" EAD, 4002 Plovdiv, Bulgaria.
¹² Department of Clinical Laboratory, Faculty of Pharmacy, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria.

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.

Keywords: anticoagulant; antimicrobial; cytotoxicity; density functional theory (DFT); galactose-assisted; phenindione (2-phenyl-1,3-indandione); silver nanoparticles; spasmolytic; thrombosis.

Grants and funding

This research and the APC were funded by the Bulgarian Ministry of Education and Science under the National Program “Young Scientists and Postdoctoral Students—2”. National Program “Young Scientists and Postdoctoral Students—2”.