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Use of Liposomes for Directed Drug Delivery against Entamoeba Histolytica
Final rept. 1 Jul 1988-30 Dec 1991
MOREHOUSE COLL ATLANTA GA
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The overall goal of this research has been to determine the feasibility and develop conditions for use of recognition specific liposomes as a means for targeted drug delivery against the intestinal parasite, Entamoeba histolytica. The specific research objectives were to identify lipid molecules of mammalian target cell membranes that stimulate phagocytosis by E. histolytica construct chemically defined liposomes that are selectively phagocytized by the parasite determine the ability of recognition specific liposomes to deliver drugs and kill E. histolytica trophozoites in culture and protect cultured mammalian cells from destruction by the parasite develop an animal model and use this to test the ability of drug loaded liposomes to eliminate the parasite in situ. Significant progress has been made on all but the last of three objectives. Two manuscripts of this work have been published and a third is in preparation. The results of this research is summarized below. The ability of purified glycosphingolipids to enhance liposome stimulated Entamoeba histolytica actin polymerization was assessed as a means to define the specificity of mammalian cell membrane lipid glycan recognition by this parasite. Synthetic liposomes containing a variety of individual glycosphingolipids bearing neutral, straight chain oligomeric glycans with galactose or N-acetylgalactosamine termini stimulated rapid 90 sec polarization of amoeba actin. Glycans with terminal N-acetylglucosamine residues were not, or only weakly, stimulatory. Glycans with glucose, N- acetylglucosamine, galactose and N-acetylgalactosamine as the penultimate residue were recognized.
APPROVED FOR PUBLIC RELEASE