GLYCOSYLATED PROTEOLIPOSOMES--A NEW DELIVERY VEHICLE

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The objective of this proposal is to examine the concept of the proteoliposome as an alternative to the liposome as a in vivo vehicle. The recent discovery of the spontaneous incorporation of integral membrane proteins into preformed unilamellar vesicles to form proteoliposomes allows, for the first time, the consideration of the proteoliposome as a feasible and economical alternative to the liposome for in vivo applications. The insertion of glycosylated integral membrane proteins derived from erythrocyte membranes, sialoglyco- and glyco-proteins, results in a stable modification of the surface of the vesicles potentially superior to that provided by the inclusion of glycolipids in liposomes; we hypothesize that the glycocalyx of these proteoliposomes can be "tailored" to result in a more persistent in vivo vehicle than that possible with a liposome composed of only lipids. It has already been shown that the proteoliposome is more stable in solution than similar liposomes; the initial aims of this study will be directed towards as examination of the relative stability of the proteoliposome versus the liposome with the components of blood. Subsequently, we will examine the intravascular persistence of various constructs of glycosylated proteoliposomes and determine whether the glycosylated proteoliposome can serve as a model for future drug delivery or hemoglobin carrier vehicles. The current aims are designed to test this concept in the most simple approach by using proteoliposomes prepared from erythrocyte integral membrane proteins derived from the same species as the recipient of the proteoliposome infusion (New Zealand rabbits), thereby avoiding most immunological complications. However, the long-term goal of this research is to construct an immunologically safe proteoliposome by synthesizing the simplest glycosylated hydrophobic (peptide) protein anchor required to provide a stable glycocalyx on the liposome by genetic engineering and/or organic synthesis.