Ethylenediamine-modified alginate - A hemocompatible platform for polymer-drug conjugates.

The study is dedicated to the synthesis, rheological properties, hemocompatibility, and further modification of water-soluble derivatives of sodium alginate containing fragments of ethylenediamine (Alg-EDA). Alg-EDA with an equal ratio of amide/amine groups and varying degrees of substitution were synthesized by the carbodiimide method. The influence of the molecular weight of Alg-EDA on the attachment of bioactive molecules such as hydroxybenzoic and ferulic acids was determined. Modification of alginate with ethylenediamine fragments leads to a reduction in dynamic viscosity and sensitivity to Ca ions (internal gelation method). Alg-EDA derivatives, with differ in molecular weight and degree of substitution with phenolic acids, are characterized by high hemocompatibility (in vitro tests: erythrocyte hemolysis, blood recalcification time, activated partial thromboplastin time). Antioxidant properties of the synthesized alginate derivatives were characterized using models of varying complexity (including cellular models). It was found that Alg-EDA, at a concentration of 0.5 mg/mL, had a statistically significant membrane-protective activity under conditions of acute oxidative stress induced by both HO and AAPH. Derivatives with lower molecular weight were more effective than high molecular weight ones. Modification of polysaccharides by the fragments of phenolic acids into the structure contributed to the enhancement of antioxidant properties. The hemocompatible macromolecular antioxidants synthesized in this study are promising for further in-depth investigation for the creation of biomedical materials.