A series of poly(ethylene glycol)-poly(dl-lactide) (PEG-PLA) block copolymers with varying molecular weights were synthesized. Drug-loaded micelles were prepared using amphotericin B (AmB) as the model drug. The PEG-PLA copolymers were freeze-dried to obtain long-term stable formulations. Saccharides at various concentrations including mannose, trehalose and glucose, Pluronic F68 and PEG were used as lyoprotectants, respectively. The protective effects of the various types of lyoprotectants on the particle size and size distribution during freeze-drying process and redispersion were investigated. The results indicated that the saccharides, Pluronic F68 and PEG all could stabilize the micellar particles in the lyophilization when the weight ratio of PLA block was smaller than that of PEG block. While the weight ratio of PLA block was bigger than that of PEG block, only steric stabilizers such as PEG and F68 were able to protect PEG-PLA micelles from the agglomeration in the freeze-drying procedure. The sustained in vitro release of AmB from PEG-PLA micelles was evidenced. The in vitro release behavior could be best described by the first order equation.

Key words: poly(ethylene glycol)-poly(dl-lactide), polymeric micelle, amphotericin B, lyophilization, in vitro release