Kazuhito Hiratani

A newly developed immunoliposome — an egg phosphatidylcholine liposome coated with pullulan bearing both a cholesterol moiety and an IgMs fragment

An improved methodology for providing a more stable and targetable drug carrier has been developed. This method involves the synthesis of a newly designed immunoliposome by coating the outermost surface of large oligolamellar vesicles of egg phosphatidylcholine with the polysaccharide pullulan, modified to carry both cholesterol, as the hydrophobic anchor, and the monoclonal antibody fragment (anti-sialosyl Lewis X, IgMs) as the sensory device. Compared with the binding of pullulan-coated liposomes, that of this immunoliposome to specific cells in vitro was significantly increased by factors of 447 to PC-9 and 295 to KATO-III, but only by a factor of 148 to the less specific cell, 3LL. This strong and specific binding of the immunoliposome to the cell surface of PC-9 was also confirmed by a fluorescence-microscopic investigation using the immunoliposome, which bore the hydrophobic fluorescent probe, terbium trisacetylacetonate, in the liposomal membrane.

Targeting Cancer therapy in Mice by Use of Newly Developed Immunoliposomes Bearing Adriamycin

AbstractPolysaccharide-coated liposomes have been developed to improve the stability of conventional liposomes against biochemical and physicochemical stimuli. Pullulan (MW 5 × 104) was used as the polysaccharide. the mouse IgM monoclonal antibody (CSLEX 1) recognizes a sialosylated Lex, which is a tumor-specific antigen in athymic mice. the IgM antibody was reduced with cysteine to obtain the subunit (IgMs) that remained biologically active. the IgMs was accumulated in an antigen-positive tumor in vivo. Subsequently, it was conjugated with the pullulan-coated liposome to form an immunoliposome.Tissue distribution studies demonstrated that immunoliposomes were more efficiently targeted to an implanted tumor than to the polysaccharide-coated liposomes. This is accompanied by a drastic decrease in liver uptake of the immunoliposomes. Furthermore, adriamycin-encapsulated immunoliposomes in-hibited the growth of the implanted tumor more effectively than did the simple pulluian-coated liposomes.