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

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

Polyelectrolyte Microcapsules as a Tool to Enhance Photosensitizing Effect of Chlorin E6

Introduction: Photodynamic therapy is a promising method of tumors treatment using photosensitizers and light of a certain wavelength. PS modification improves and enhances the phototoxic effect with decreased dark cytotoxicity. Materials and Methods: We compared the photosensitizing effect of polyelectrolyte microcapsules with chlorin E6 (ClE6) and free ClE6 at equivalent concentrations on murine fibroblast culture L929 using in vitro tests. Microcapsules were prepared layer by layer, sequentially depositing oppositely charged polyelectrolytes onto spherical CaCO3 particles. Cellular uptake of capsules was assessed using confocal microscopy. MTT test was used for a study of cell viability, and the relative amount of ROS was determined by the fluorescent method. Results: Microcapsules with ClE6 (in all tested concentrations) after exposure to red light (660 nm) reduced cell viability from 20% to 5%, while these capsules did not have dark cytotoxicity. Free ClE6 at the same concentrations as in the capsules after irradiation reduced viability from 65% to 35%. The level of ROS in the group of cells with capsules was 2 times higher compared to the group with CLE6. Discussion: The most probable mechanism of toxicity increase is creation of a higher ROS concentration and effect localization in the area of microcapsule interaction with the cell membrane. ROS production activation may stem from capsules providing a higher local PS concentration in the cell or nearby than the drug’s free form. Conclusion: The inclusion of chlorin E6 in polymer capsules reduced dark toxicity and increased the photosensitizing effect compared to the free form of ClE6