CROSS-LINKING OF HYALURONIC-ACID WITH WATER-SOLUBLE CARBODIIMIDE

Hyaluronic acid (HA) was chemically crosslinked with a water-soluble c arbodiimide (WSC) to produce low-water-content films when brought into contact with water. The crosslinking reaction was performed in two di fferent ways; one was by using HA films and the other by casting HA so lutions. Both methods produced water-insoluble HA films. The lowest wa ter content of the crosslinked KA films subjected to swelling with wat er was 60 wt % at 37 degrees C, which was lower than any reported valu es. Infrared spectra of the crosslinked films suggested that intermole cular formation of ester bonds between the hydroxyl and carboxyl group s belonging to different polysaccharide molecules led to crosslinking. For comparison, pectin which possesses hydroxyl and carboxyl groups i n one molecule, similar to HA, was subjected to crosslinking with WSC. The finding on pectin also supported ester formation between differen t polysaccharide molecules. The crosslinking of HA film with WSC in th e presence of L-lysine methyl ester prolonged the in vivo degradation of HA film, probably because of amide bond formation as the crosslink. (C) 1997 John Wiley & Sons, Inc.