The objective of the proposed research is to investigate several important factors which can influence the release of liposome- associated materials (via encapsulation and/or covalent conjugation) within macrophages. The program is geared to develop some novel methods of liposome formulation and to apply the technique of gamma-ray perturbed angular correlation for investigating the rate and extent of release of liposome- associated materials within macrophages. The focus is on investigating the kinetic aspects of the release of liposome- associated materials within macrophages, such that the results of proposed basic study will lead to a rational approach to """"""""fine tune"""""""" the regimen of using activated tumoricidal macrophages for combating cancer. The goal of the proposed research will encompass the following specific studies: 1. How the lamellae of multilamellar liposomes affect the macrophage-mediate release or (i) small, water soluble molecules entrapped in liposomes and (ii) small molecules covalently bound to the surface of liposomes; 2. What the rate and extent of macrophage-mediate release of liposome-associated materials from the """"""""multivesicular"""""""" liposomes are; 3. The pharmacological effects of the """"""""cytoplasmic"""""""" liposome- associated muramyldi-peptide (MDP) on macrophage activation; and 4. The fate of liposomes which are in the cytoplasm of macrophages.
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