Red blood cells covalently bound with polymers
Living cells modified at their surface with specially selected polymers are disclosed. A simple method to covalently attach specially selected PEG derivatives to the surface of RBC in aqueous media under mild conditions is a preferred example. The selected PEG-modification dramatically reduced aggregation and low shear viscosity of RBC resuspended in autologous plasma, and inhibited RBC agglutination by blood group-specific antibodies. The morphology and deformability of the PEG-treated cells were unaltered. The PEG coating of the RBC surface is applicable to the treatment of a variety of diseases characterized by vaso-occlusion or impaired blood flow, e.g., myocardial infarction, shock, and sickle cell disease.
1. A physiologically compatible solution for infusion comprising:
red blood cells covalently labelled with a copolymer of oxyethylene and oxypropylene.
2. The solution of claim 1 wherein the copolymer has a molecular weight between approximately 2,000 and 50,000.
3. The solution of claim 1 wherein the copolymer is a block copolymer.
4. The solution of claim 1 wherein the copolymer is a tri-block copolymer.
5. The solution of claim 4 wherein the tri-block copolymer is a poloxamer.
6. The solution of claim 5 wherein the poloxamer is poloxamer 108.
7. The solution of claim 5 wherein the poloxamer is poloxamer 188.
8. The solution of claim 5 wherein the poloxamer is poloxamer 288.
9. A physiologically compatible solution for infusion comprising:
red blood cells covalently labelled with a copolymer of oxyethylene and oxybutylene.
10. The solution of claim 9 wherein said copolymer is a block copolymer.
11. The solution of claim 10 wherein said copolymer is a tri-block copolymer.
12. The solution of claim 11 wherein said tri-block copolymer has a molecular weight between approximately 4,000 and 50,000.
13. A method to treat a pathological condition comprising:
identifying a disorder treatable by altering blood viscosity, and
altering blood viscosity by administering the composition of any of claims 1 - 12 .
14. The method of claim 13 wherein the condition is selected from the group consisting of sickle cell disease, myocardial infarction, shock, ischemic vascular disorder, a peripheral vascular disease.
15. The method of claim 14 further comprising administering a thrombolytic agent.