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 16h at 25 or 60 degrees C. The (1)H NMR spectrum of octenyl succinic anhydride modified HA (OSA-HA) was elucidated using 20 NMR ((1)H,(1)H g-COSY) spectroscopy. The modification was confirmed and the degree of substitution (DS) 01 1.5-19% was determined using (1)H 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 (gamma) was done on 0.01-1% OSA-HA (M(w) = 30,000 g/mol, DS = 19%) showing gamma < 50 Nm/m. Titration of the surface tension was done with OSA-HA (DS = 19%, M(w) = 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 24h and 3 weeks after storage dark at ambient temperature. The ASA-HA stabilized emulsions better than non-modified HA due to their surface activity. (C) 2011 Elsevier Ltd. All rights reserved.