TARGETED LIPOSOMES AND METHODS FOR LIPOSOME-PROTEIN COUPLING

摘要

This invention relates to a method for synthesizing a substantially pure reactive lipid including, for example, N--4-(p-maleimidophenyl)-butyryl!phosphitadiylethanolamine (MPB-PE) and related compositions. The compositions of the present invention are useful as coupling agents and may be incorporated into liposomes and subsequently coupled to proteins, cofactors and a number of other molecules. A preferred coupling method is also disclosed as are protein conjugates. The present invention also relates to a general method for producing sized protein-liposome conjugates exhibiting enhanced blood circulation times. The present invention also relates to the sized protein-liposome conjugates compositions produced by the method of the present invention. The protein-liposome conjugates of the present invention preferably range in size from about 75 nm to about 200 nm. The liposomes of the invention may have a trans-membrane potential across their membranes, and may be dehydrated. In addition, the composition may contain ionizable bioactive agents, such as antineoplastic agents, and may be used in diagnostic assays.