Amphiphilic chitosan-polyaminoxyls loaded with daunorubicin: Synthesis, antioxidant activity, and drug delivery capacity.

Autor: Sen' VD; Institute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka 142432, Russian Federation; P.G. Demidov Yaroslavl State University, Yaroslavl 150000, Russian Federation. Electronic address: senvd@icp.ac.ru., Balakina AA; Institute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka 142432, Russian Federation., Stupina TS; Institute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka 142432, Russian Federation., Mumyatova VA; Institute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka 142432, Russian Federation., Kulikov AV; Institute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka 142432, Russian Federation., Tikhonov IV; P.G. Demidov Yaroslavl State University, Yaroslavl 150000, Russian Federation., Terent'ev AA; Institute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka 142432, Russian Federation; P.G. Demidov Yaroslavl State University, Yaroslavl 150000, Russian Federation., Pliss EM; P.G. Demidov Yaroslavl State University, Yaroslavl 150000, Russian Federation.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2021 Dec 15; Vol. 193 (Pt A), pp. 965-979. Date of Electronic Publication: 2021 Oct 30.
DOI: 10.1016/j.ijbiomac.2021.10.170
Abstrakt: 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 R h 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 (IC 50  > 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.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: