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

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.

Substituted p-hydroquinones as inhibitors of lipid peroxidation.

The technique based on monitoring oxygen consumption was applied to study 12 alkyl- and methoxy-substituted p-hydroquinones (QH(2)) as a chain-breaking antioxidant during the oxidation of styrene and methyl linoleate (ML) in bulk as well as ML oxidation in micellar solution of sodium dodecyl sulfate (SDS) at 37 degrees C. The antioxidant activities of QH(2) were characterized by two parameters: the rate constant k(1) for reaction of QH(2) with the peroxy radical LO(2)*: QH(2)+LO(2)*-->QH*+LOOH and the stoichiometric factor of inhibition, f, which shows how many kinetic chains may be terminated by one molecule of QH(2). In the case of styrene and ML oxidation in bulk, f values never exceed two; for the majority of QH(2), f was found to be significantly less than two due to the interaction of QH* with molecular oxygen. In the absence of superoxide dismutase (SOD), all the studied QH(2) displayed a very moderate if any antioxidant capability during ML oxidation in SDS micelles. When 20U/ml SOD was added, the majority of QH(2) showed a pronounced ability to inhibit ML oxidation, f parameter being ca. one. The features of QH(2) as an antioxidant in aqueous environment are suggested to associate with the reactivity of semiquinone (Q*(-)). Q*(-) reacts readily with molecular oxygen with formation of superoxide (O(2)*(-)); further reactions of O(2)*(-) result in fast depleting QH(2) and chain propagation. The addition of SOD results in purging a reaction mixture from O(2)*(-) and, as a corollary, in depressing undesirable reactions with the participation of O(2)*(-). With all the oxidation models, QH(2) were found to be very reactive to LO(2)*. The rate constants k(1) decreased progressively when going from the oxidation of styrene to ML oxidation in bulk and further to ML oxidation in SDS micelles.