The goal of this research is to use liposomes to deliver their contents into the cytoplasm of cells, to characterize the mechanism of delivery and to exploit the low pH environment of the endosome or lysosome to catalyze delivery of liposomal contents into cytoplasm. One approach is to synthesize novel peptides that can undergo a low pH induced conformational change that results in the exposure of hydrophobic sequences that initiate membrane fusion. The peptide would be attached to the surface of the liposome in this application. A second approach is to synthesize prodrugs that can undergo either a pH dependent or enzymatic modification which permits their efflux from the lysosomal compartment. In either of these applications chemical and physical approaches are being used to design more efficient drug delivery systems and to determine the limitations to their use.
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