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Immunoliposomes As Drug Delivery System
Abstract
Summary:
Substances which have immunological properties are recently being used to define target cells and non-target cells, with drug delivery systems. Among these drug delivery systems, liposomes are the most promising ones. Because, the similarity between the cell membrane and bilayer structure of liposomes is an important advantage for the liposomes. As an other advantage, liposomes can be combined with immunoglobuniles, so that they are put on target more spesifically.
In this review article, spesification of immunoliposomes used as drug delivery system both in the form of liposome and immunoglobuline separately, in vivo-in vitro studies about this subject, developments in their therapeutic usage and the points must be studied moreover had been reviewed. Immunoliposomes seem to be promising in treatment of blood diseases such as lenfoma, leucemia and thalasemia, decreasing the toxic levels of drugs in circulatory system, development of gama scintigraphy studies. Development of immunoliposomes as drug delivery system, administration of different immunoliposomes in different pathologic situations will be the points which is going to determine the future of immunoliposomes.
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Two rat monoclonal antibodies, 34A and 201B, which specifically bind to a surface glycoprotein (gp112) of the pulmonary endothelial cell surface, have been coupled to unilamellar liposomes of approximately 0.25 microns in diameter. The 34A- and 201B-liposomes (monoclonal antibodies 273-34A and 411-201B, respectively), but not antibody-free liposomes and liposomes coupled to 14, a nonspecific monoclonal antibody, accumulate efficiently (approximately 30% injected dose) in the lung of mice which have been injected via the tail vein. Immunoliposome targeting to lung is demonstrated both by using a 125I-labeled lipid marker and an entrapped water-soluble marker. Lung accumulation of 34A-liposomes is completely blocked by a preincubation of free antibody 34A, but not antibody 14, indicating that the immunoliposome accumulation at the target site is immunospecific. Time course studies have revealed that 34A-liposomes bind to lung antigens within 1 min after injection, indicating that the target binding takes place during the first few passages of immunoliposomes through the lung capillary bed. Unbound immunoliposomes are taken up by liver and spleen within 3-5 min after injection. The level of lung accumulation increases significantly as the protein:lipid ratio of the immunoliposome increases. Approximately 50% of injected dose is accumulated in lung for 34A-liposomes, with an average of 935 antibody molecules per liposome. Immunoliposomes of larger size accumulate in lung more significantly than those of smaller size. Injection with higher doses also enhances the level of lung accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
The modern concept of liposomes as models of lipid bilayers of cell membranes was established in a landmark paper by Bangham et al (8). Shortly thereafter, starting in 1968, a related field was established that dealt with a specialized area of liposome research that has been loosely referred to as“immunologic aspects of liposomes.” Based on an analysis of the literature through 1980 it was projected that the publication rate in the field of immunology of liposomes would reach 200 papers per year in 1983 (4). Extrapolation of the growth rate published in 1983 now leads to the further prediction that if growth were maintained at the same rate 670 papers would appear in 1987 and 910 papers in 1988.
Antibody-bearing or control liposomes were injected intravenously into mice which expressed a determinant recognized by the antibody, or control mice lacking the determinant. Antibody-bearing liposomes in mice lacking the determinant circulated for the same period as control liposomes, but antibody-bearing liposomes in mice expressing the targeted determinant rapidly disappeared from the plasma. The rate at which liposomes were cleared was related to the number of cells expressing the target determinant. Multiple injections of antibody-bearing liposomes failed to induce an anti-idiotypic response in mice, though a strong response was elicited in mice injected with the antibody in complete Freund's adjuvant. The circulation of control and antibody-bearing liposomes in mice immunized several times with liposomes bearing the same antibody was similar to that of uninjected mice.
The current status of efforts to target cytotoxic agents to tumor cells using antitumor antibodies and particulate drug carriers such as liposomes and microspheres is reviewed. Emphasis is given to the role of anatomic and physiologic factors in determining the disposition, fate, and therapeutic efficacy of targeted drug delivery systems and to the importance of tumor cell heterogeneity as a major obstacle to effective cancer therapy.