感染症とＤＤＳ リポソームによる抗菌薬製剤設計

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. Several kinds of carrier system, such as liposomes, microsphere and polymer micelles, have been developed to resolve the problems. Liposomal formulations of AmB, which make it possible to reduce its toxicity and improve the therapeutic efficacy, have been developed and now on the market in USA and Europe. But, further improvements of the encapsulation of AmB in 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 are required for the high encapsulation efficacy. AmB-encapsulating 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-PEG liposomes showed the higher therapeutic effects on murine model of pulmonary aspergillosis than that of commercially used liposomes. Many experiments on the encapsulation of antimicrobial agents in liposomes have been demonstrated, but there are not so much drugs-carrier system applied for therapy. Determination of the optimum functional carrier system should be important for the practical uses.