Abstract: According to drug retention, diameter change, glass-transition temperature (Tg) of lyophilized liposomes and the interaction of phospholipid and carbohydrates, the protective effects and mechanisms by trehalose and hyaluronic acid (HA) were examined. Bilayer fusion and drug leakage induced by lyophilization are inhibited by trehalose, lactose, sucrose, HA and the combination of trehalose and HA. The capacity of HA alone to protect liposomes is low, however, the combination of trehalose and HA is more effective than the two additives used alone. There is interaction between trehalose and phospholipid after lyophilization. This interaction is formed between -OH groups of trehalose and PO2- groups of phospholipid by hydrogen bonding. Trehalose and HA offer complementary properties when the two types of additives are used together. The combination of "water replacement" produced by trehalose and "glassy state" produced by HA results in the optimal protective effects.

Key words: trehalose, hyaluronic acid, membrane lipid bilayer, protective effect