Fibrin targeting of tissue plasminogen activator-loaded echogenic liposomes.
We recently reported entrapment of tissue-plasminogen activator (tPA) into echogenic liposomes (ELIP) with retention of echogenicity and thrombolytic effect. Integral to the potential of this agent for ultrasound-detectable local drug delivery is the specific binding of tPA-ELIP to clots. tPA contains fibrin-binding sites; we hypothesized that tPA when associated with ELIP, will maintain fibrin binding properties, rendering further manipulation for targeting of the tPA-ELIP unnecessary. We demonstrated strong fibrin binding of the ELIP-associated tPA. Fibrin binding for ELIP-associated tPA was twice that of free tPA. This strong affinity for fibrin was confirmed using echogenicity analysis of porcine clots in vitro. Both objective (mean gray scale analysis) and subjective (visual estimation by two experienced echocardiographers) evaluation of the clots showed enhanced highlighting of clots treated with tPA-ELIP when compared to control. The findings in this study represent new approaches for fibrin-targeted, ultrasound-directed and enhanced local delivery of a thrombolytic agent.
Tiukinhoy-Laing
Susan D
SD
Division of Cardiology, Department of Internal Medicine, University of Texas at Houston, 6431 Fannin Street, MSB 1.246, Houston, TX 77030, USA. susan.t.laing@uth.tmc.edu
Buchanan
Kyle
K
Parikh
Devang
D
Huang
Shaoling
S
MacDonald
Robert C
RC
McPherson
David D
DD
Klegerman
Melvin E
ME
D000818:Animals; D004337:Drug Carriers; D005340:Fibrinogen / Q000378:metabolism*; D008081:Liposomes; D013552:Swine; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000378:metabolism
D004337:Drug Carriers; D008081:Liposomes; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator