Photodynamic agents which exhibit virucidal activity have been investigated for use with cellular blood components, using platelets as a model cell system. The effect of the photosensitizer merocyanine 540 MC 540) on platelets and on marker viruses was examined in order to assess its potential in reducing virus transmission by blood products. The results of this study demonstrated several deleterious effects of the dye (4-24ug/mL) on platelet morphology and function in both the absence and presence of visible light (450-600nm). Platelets treated with MC 540 and light in the presence of concentration of albumin < 0.35% aggregated spontaneously without added thrombin (i.e., in the absence of agonist). A normal response of MC-treated platelets to thrombin was observed only upon addition of 5% albumin to the platelet suspension medium. Platelet activation by MC 540 and light was accompanied by serotonin release. Platelets treated with 15 ug MC 540/mL in albumin-free medium released 51% serotonin in the dark and 93% serotonin upon light exposure. Full protection against serotonin release was provided by 2.55 albumin in the medium. The antiviral activity of MC 540 and light was examined by using the lipid-containing viruses herpes simplex virus (HSV) and bacteriophages phi and PM2. Of the lipid-enveloped viruses, HSV was 25 times more sensitive to MC 540 and light than was phi 6. PM, with an internal lipid layer, was almost 300 times less sensitive to dye and light treatment than was HSV. Photoinactivation of phi 6 and PM2 was completely prevented by the addition of 5% albumin to the medium. Under identical conditions, HSV was still inactivated but was nearly 200 times less sensitive. Therefore, concentration of albumin which protect platelets form photodamage significantly reduce the antiviral activity of MC. Results of this study were published in the Transfusion 1991;31:415-422. A summary of procedures of viral inactivation including this work was published as an Editorial in Transfusion 1990;30:480-481. Also, these results were discussed in an invited presentation at the American Society for photobiology meeting in June, 1991 in San Antonio, TX. A manuscript will be published in Blood Cells.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Intramural Research (Z01)
Project #
1Z01BH001011-04
Application #
3804876
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Center Biologics Evaluation Research Hematology
Department
Type
DUNS #
City
State
Country
United States
Zip Code