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Curr Pharm Des. 2002;8(6):441-54.
Pharmaceutical design of the liposomal antimicrobial agents for infectious disease.
Moribe K, Maruyama K.
School of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa, Japan.
From the point of view of pharmaceutical design, development of carrier system of antimicrobial agents with functional properties should be required. We introduced here the development-process of liposomal formulations of polyene macrolide antibiotics, amphotericin B (AmB) and nystatin as injectable dosage forms. Both development of the effective encapsulation method of these drugs in liposomes and investigation of the encapsulation mechanism and the molecular states of them are important to determine the optimum lipid composition for therapeutic uses. Enhanced encapsulation of these hydrophobic drugs, long-circulation in blood and high targetability are the required functional properties for the carrier system. Low encapsulation of AmB in liposomes has been overcome by the incorporation of polyethylene glycol-lipid derivatives, DSPE-PEG. Both the hydration with 9% sucrose solution and the complex formation between AmB and DSPE-PEG contribute not only to the enhanced encapsulation of AmB in liposomes but also to the stability and long-circulation properties in blood. Encapsulation mechanism and the molecular states of AmB in liposomes were also investigated by several methods. AmB-encapsulating PEG liposomes (PEG-L-AmB) with optimum lipid composition also showed reduced toxicity and higher therapeutic efficacy on murine model of pulmonary aspergillosis than that of conventionally used AmB formulations. Further enhanced therapeutic effects was observed by using AmB-encapsulating PEG immunoliposomes (34A-PEG-L-AmB) carrying monoclonal antibodies at the distal ends of the PEG chains. On the contrary to AmB, encapsulation characteristics of nystatin were apparently different from that of AmB, though the chemical structure is very similar. Self-association of nystatin with sterol-free lipid membrane dominantly influences on the encapsulation characteristics. Many experiments about the encapsulation of antimicrobial agents in liposomes have been demonstrated by many researchers, but there are not so much drugs developed for commercially used. Optimization of the formulation of functional drug-carrier system should be important for the practical uses.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12069381&dopt=Abstract [PubMed - in process]
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