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        Antibody Conjugation Methods for Active Targeting of Liposomes

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        1709
        Liposomes are useful drug delivery vehicles since they may protect encapsulated drugs from enzymatic degradation and rapid clearance in vivo, or alter biodistribution, potentially leading to reduced toxicities (1 ,2 ). A major limitation to the development of many specialized applications is the problem of directing liposomes to tissues where they would not normally accumulate. Consequently, a great deal of effort has been made over the years to develop liposomes that have targeting vectors attached to the bilayer surface. These vectors have included ligands such as oligosaccharides (3 ,4 ), peptides (5 ,6 ), proteins (7 ,8 ) and vitamins (9 ). Most studies have focused on antibody conjugates since procedures for producing highly specific monoclonal antibodies (MAbs) are well established. In principle it should be possible to deliver liposomes to any cell type as long as the cells are accessible to the carrier. In practice it is usually not this simple since access to tissue, competition, and rapid clearance are formidable obstacles. It has also been shown that antibodies become immunogenic when coupled to liposomes (10 ,11 ), although in similar experiments with ovalbumin we have demonstrated that immunogenicity can be suppressed by formulating the liposomes with the cytotoxic drug doxorubi-cin (12 ). Such issues as these suggest that the development of antibody-targeted liposomes for in vivo applications will present difficult challenges.
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