A Platelet Substitute - the Plateletsome to Be Used in Transfusion Therapy
Abstract
This project was defined as a feasibility study to establish a foundation on which a liposome based platelet substitute could be developed. In the first year of this contract, platelet membrane glycoproteins (GP) and IIb- IIIa were isolated and incorporated into phospholipid vesicles as a heterodimer complex. GP Ib was purified by Triton solubilization of platelet membranes and affinity chromatography. The outside-out orientation of these glycoproteins in the liposomal vesicles, which were prepared by reverse-phase sonication, was confirmed by antibody and ligand binding studies. The calcium channel function of GPII-IIIa in liposomes and ligand binding inhibition of this channel were characterized with Fura-2 loaded liposomes. The ability of these GP bearing liposomes to form aggregates and to participate in platelet aggregate formation was confirmed. The expression of neoantigens on the surface of these liposomes was assessed. A model system was developed to evaluate the adhesive properties of glycoproteins bearing liposomes in vitro under gravity and shear conditions. It was determined that maximum adhesion occurred with a composite liposome preparation bearing multiple platelet membrane GP. A liposome preparation based on a composite preparation of 12 different platelet membrane GP caused significant amelioration of bleeding in animal models (42% reduction). (jg)
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 15, 1989
- Accession Number
- ADA217793
Entities
People
- Mary E. Rybak
Organizations
- University of Massachusetts