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

Author:

Nikolova Stoyanka1ORCID,Milusheva Miglena12ORCID,Gledacheva Vera3ORCID,Feizi-Dehnayebi Mehran4ORCID,Kaynarova Lidia5ORCID,Georgieva Deyana5ORCID,Delchev Vassil6,Stefanova Iliyana3ORCID,Tumbarski Yulian7,Mihaylova Rositsa8,Cherneva Emiliya910ORCID,Stoencheva Snezhana1112,Todorova Mina1ORCID

Affiliation:

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.

Funder

the Bulgarian Ministry of Education and Science under the National Program “Young Scientists and Postdoctoral Students—2”

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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