The objective of the proposed research is the characterization of the multiple pathways of the uptake and degradation of liposomes in the liver at the cellular level. The program is geared to apply the method of centrifugal elutriation for fractionating liver cells, the technique of gamma ray perturbed angular correlation, and other bioanalytical methods for investigating the influence of the dose of liposomal lipid and other properties of liposomes on various pathways of uptake and degradation of liposomes and their entrapped contents in the liver. The focus is on studying various approaches of regulating the pathways of uptake and degradation of liposomes in tissue culture systems, in the system of a perfused liver, and in rats and mice in vivo.
The specific aims of the proposed research program are directed toward the following two main areas: (1) to investigate how the delivery of liposomes and their content to the lysosomal and the cytoplasmic compartment of the parenchymal cells, and to the endothelial and Kupffer cells are regulated by the presence of terminated-galactose glycolipids and lipophilic insulin derivatives in liposomes under various formulating and dosing conditions. (2) to study how the rate and extent of release of liposomal content are regulated by where and how the liposomes are degraded at various cellular sites of uptake.
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