New amphiphilic hyaluronan derivatives based on modification with alkenyl and aryl succinic anhydrides

Hyaluronic acid (HA) of various molecular weights (4000, 14,000, 30,000, 100,000 and 850,000 g/mol) was modified with aryl and alkenyl succinic anhydrides (ASA). The modifications were conducted at pH 8.0–8.5 for 16 h at 25 or 60 °C. The 1H NMR spectrum of octenyl succinic anhydride modified HA (OSA-HA) was elucidated using 2D NMR (1H,1H g-COSY) spectroscopy. The modification was confirmed and the degree of substitution (DS) of 1.5–19% was determined using 1H NMR spectroscopy. Light scattering (SEC-MALLS-RI) showed that negligible degradation of HA had occurred during the modification procedure. Further, dynamic measurements of surface tension (γ) was done on 0.01–1% OSA-HA (Mw = 30,000 g/mol, DS = 19%) showing γ < 50 Nm/m. Titration of the surface tension was done with OSA-HA (DS = 19%, Mw = 30,000) in 0.1 M NaCl, giving a critical aggregation concentration (CAC) of 25 g/L, showing that ASA-HAs form micelles/aggregates above a certain concentration. The emulsifying properties of the ASA-HA derivatives were evaluated in a test formulation of 30% oil phase and 70% water phase (containing 0.1 M NaCl and 0.2% ASA-HA). The stability of the emulsions was evaluated by visual inspection after 24 h and 3 weeks after storage dark at ambient temperature. The ASA-HA stabilized emulsions better than non-modified HA due to their surface activity.