Amphiphilic chitosan–polyaminoxyls loaded with daunorubicin: Synthesis, antioxidant activity, and drug delivery capacity
| Autor: | Victoriya A. Mumyatova, A. A. Balakina, E. M. Pliss, Tatyana S. Stupina, Vasily D. Sen, Alexander V. Kulikov, I. V. Tikhonov, A. A. Terent’ev |
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| Rok vydání: | 2021 |
| Předmět: |
Cell Survival
Daunorubicin Biochemistry Micelle Antioxidants Chitosan chemistry.chemical_compound Sulfation Structural Biology Cell Line Tumor Amphiphile medicine Humans Cytotoxicity Molecular Biology Micelles Drug Carriers Antibiotics Antineoplastic Chemistry General Medicine Combinatorial chemistry Solubility Critical micelle concentration Drug delivery medicine.drug |
| Zdroj: | International Journal of Biological Macromolecules. 193:965-979 |
| ISSN: | 0141-8130 |
| Popis: | The binding of aminoxyls to polymers extends their potential use as antioxidants and EPR-reporting groups and opens up new horizons for tailoring new smart materials. In this work, we synthesized and characterized non-sulfated and N-sulfated water-soluble amphiphilic chitosans with a critical micelle concentration of 0.02–0.05 mg/mL that contain 13–18% of aminoglycosides bound with various aminoxyls. Chitosan–polyaminoxyls (CPAs) formed micelles with hydrodynamic radii Rh of ca. 100 nm. The EPR spectra of CPAs were found to depend on the rigidity of the aminoxyl–polymer bond and structural changes caused by sulfation. CPAs demonstrated antioxidant capacity/activity in three tests against reactive oxygen species (ROS) of various nature. The charge of micelles and structure of aminoxyls significantly affected their antioxidant properties. CPAs were low toxic against tumor (HepG2, HeLa, A-172) and non-cancerous (Vero) cells (IC50 > 0.8 mM of aminoglycosides). Sulfated CPAs showed better water solubility and the ability of binding and retaining the anti-tumor antibiotic daunorubicin (DAU). DAU-loaded micelles of CPAs (CPAs–DAU) demonstrated a 1.5–4-fold potentiation of DAU cytotoxicity against several cell lines. CPAs–DAU micelles were found to affect the cell cycle in a manner markedly different from that of free DAU. Our results demonstrated the ability of CPAs to act as bioactive drug delivery vehicles. |
| Databáze: | OpenAIRE |
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