Abstract
Amphotericin B (AmB), polyene macrolide antibiotics, has been used for the treatment of systemic fungal infections. It is necessary to administer at higher dosage to treat pulmonary aspergillosis, however, its clinical use is limited by toxic side effects. Liposomal formulation of AmB make it possible to reduce its toxicity and improve the therapeutic efficacy and recently, liposomal and lipid formulation of AmB have been developed and now on the market in USA, Europe and Japan. But, further improvements of the encapsulation of AmB into liposomes and therapeutic efficacy have still been required. Enhanced encapsulation of AmB in liposomes by complex formation between AmB and polyethylene glycol-lipid derivatives, DSPE-PEG, has clearly solved the problems, which have been investigated by us. Hydration by 9% sucrose solution and incorporation of DSPE-PEG were required for the high encapsulation efficacy. AmB-PEG liposomes showed not only high encapsulation of AmB but also high retention of AmB in liposomes in vitro and long-circulation property in vivo.
We also prepared the novel AmB encapsulating PEG-immunoliposomes carrying monoclonal antibodies at the distal ends of the PEG chains. AmB-PEG-immunoliposomes and AmB-encapsulating PEG liposomes also showed the higher therapeutic effects on murine model of pulmonary aspergillosis than that of commercially used liposomes.
