Encapsulation of the thrombolytic enzyme, brinase, in photosensitized erythrocytes: a novel thrombolytic system based on photodynamic activation.
In order to circumvent many of the problems associated with the systemic administration of agents used in thrombolytic therapy, it was decided to investigate the possibility of using erythrocytes as carriers and delivery vehicles for these agents. The enzyme brinase, a fibrinolytic enzyme produced by Aspergillus oryzae, was loaded into rabbit erythrocytes using electroporation. The loading index for this enzyme was found to be 60% and incorporation appeared to be relatively stable over a period of 4 h. In order to facilitate the predetermined release of the loaded component from the erythrocytes, they were photosensitized using haematoporphyrin derivative (HPD) and release was demonstrated within 5 min of photoactivation. Inclusion of the loaded, photosensitized system into clotting blood and subsequent exposure to light demonstrated almost complete lysis of the clot. We believe that this system exhibits potential for use in thrombolytic therapy.
Flynn
G
G
Biotechnology Group, School of Applied Biological and Chemical Sciences, University of Ulster, Coleraine, Co. Londonderry, UK.
Hackett
T J
TJ
McHale
L
L
McHale
A P
AP
D000818:Animals; D001236:Aspergillus oryzae / Q000201:enzymology; D001954:Brinolase / Q000008:administration & dosage*; D002214:Capsules; D004337:Drug Carriers; D018274:Electroporation / Q000379:methods; D004912:Erythrocytes / Q000187:drug effects; D017324:Hematoporphyrin Derivative / Q000494:pharmacology*; D007700:Kinetics; D007834:Lasers; D011817:Rabbits; D015912:Thrombolytic Therapy / Q000379:methods*
D002214:Capsules; D004337:Drug Carriers; D017324:Hematoporphyrin Derivative; D001954:Brinolase