Grafting of steroids to hyaluronan towards the design of delivery systems for antioxidants: The role of hydrophobic core

•Mixed anhydrides methodology allows the conjugation of steroids to hyaluronan.•Conjugates steroids and HA of degree of substitution up to 25% are water soluble.•The hydrophobicity of cholesterol increased encapsulation efficiency.•Encapsulation of antioxidants in the amphiphilic conjugates was demonstrated.•The turbidity of the solutions increases as a function of the degree of modification. In this work, amphiphilic hyaluronic acid (HA) was synthesized by the chemical bonding of steroids. Particularly, succinyl cholesterol (SCH), cholic acid (CA), deoxycholic acid (DOCA), and 18β-glycyrrhetinic acid (GA) were activated by benzoyl chloride towards the esterification reaction of HA in water. The degree of substitution can be controlled by varying the feed ratio of mixed anhydride to HA and up to 25% (mol/mol) can be obtained. Due to mild reaction conditions, no degradation of the polysaccharide was observed. The prepared amphiphilic polymers were characterized by NMR, infrared spectroscopy (FT-IR) and SEC/MALLS, as well as turbidity and size of the aggregates. The developed system is proposed for the delivery of hydrophobic drugs; for this purpose, curcumin, vitamin E and coenzyme Q10 were used as hydrophobic models; these molecules were loaded into the conjugates with high efficiency. The loading capacity was a function of degree of substitution. Furthermore, the biocompatibility of the derivatives and the cellular uptake of the delivery system enabled us to demonstrate the potential of the prepared delivery systems.