Amylase-Sensitive Polymeric Nanoparticles Based on Dextran Sulfate and Doxorubicin with Anticoagulant Activity

• Main Authors: Nikolay A. Pyataev, Pavel S. Petrov, Olga V. Minaeva, Mikhail N. Zharkov, Oleg A. Kulikov, Axeksandr V. Kokorev, Ekaterina P. Brodovskaya, Ivan A. Yurlov, Ilya V. Syusin, Andrey V. Zaborovskiy, Larisa A. Balykova
• Format: Article
• Language: English
• Published: MDPI AG 2019-05-01
• Series: Polymers
• Subjects: doxorubicin; dextran sulfate; nanoparticles; amylase; cytotoxicity; ascitic hepatoma; heparin-like effect
• Online Access: https://www.mdpi.com/2073-4360/11/5/921

This study looked into the synthesis and study of Dextrane Sulfate−Doxorubicin Nanoparticles (DS−Dox NP) that are sensitive to amylase and show anticoagulant properties. The particles were obtained by the method of solvent replacement. They had a size of 305 ± 58 nm, with a mass ratio of DS:Dox = 3.3:1. On heating to 37 °C, the release of Dox from the particles was equal to 24.2% of the drug contained. In the presence of amylase, this ratio had increased to 42.1%. The study of the biological activity of the particles included an assessment of the cytotoxicity and the effect on hemostasis and antitumor activity. In a study of cytotoxicity on the L929 cell culture, it was found that the synthesized particles had less toxicity, compared to free doxorubicin. However, in the presence of amylase, their cytotoxicity was higher than the traditional forms of the drug. In a study of the effect of DS−Dox NP on hemostasis, it was found that the particles had a heparin-like anticoagulant effect. Antitumor activity was studied on the model of ascitic Zaidel hepatoma in rats. The frequency of complete cure in animals treated with the DS−Dox nanoparticles was higher, compared to animals receiving the traditional form of the drug.