A Platelet Substitute: The Plateletsome to be Used in Transfusion Therapy
Abstract
The goal of this project is to establish a foundation on which to develop a liposome-based platelet substitute in transfusion therapy. Platelet membrane glycoproteins IIb and IIIa isolated and incorporated into phospholipid vesicles as a heterodimer complex. Glycoprotein Ib was also purified by Triton solubilization of platelet membranes and affinity chromatography. The out-side out orientation of these glycoproteins in the liposomal vesicles, which were prepared by reverse-phase/sonication, was confirmed by antibody binding, ligand binding, and monoclonal antibody binding. The expression of neoantigens on the surface of these liposomes was assessed. None could be detected by immune lysis assay in rabbit immunized with IIb-IIIa liposomes of soluble liposomes. GP IIb- IIIa liposomes did not activate humoral coagulation and did not induce platelet aggregation in vitro. In addition, no activation of coagulation in vivo could be detected. A model system was developed to evaluate the adhesive function of GP- liposomes in vitro under gravity and shear conditions. GP IIb-IIIa lipsomes were shown to adhere effectively to de-endothelialized aorta and surfaces coated with vWF and fibrinogen. A thrombocytopenic rat model was developed to be utilized in in vivo studies of hemostatic efficacy of various liposome preparations in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 25, 1988
- Accession Number
- ADA202549
Entities
People
- Mary E. Rybak
Organizations
- University of Massachusetts