Local release of fibrinolytic agents for adhesion prevention.
Tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), and streptokinase were evaluated for their ability to reduce postsurgical adhesion formation in a rat uterine horn devascularization and serosal injury model in a blinded, randomized study. Small doses of tPA, uPA, or streptokinase were delivered over approximately a 4-day period either from a biodegradable hydrogel matrix or as four daily intraperitoneal injections. The hydrogel was formed upon the uterine horns by photopolymerization of an aqueous precursor solution containing dissolved drug. A control group that received no treatment had an average extent of adhesion formation of 72 +/- 15% (mean +/- SEM, percentage of the length of the uterine horns involved in adhesions). Application of this formulation of the hydrogel alone reduced the extent of adhesion formation to 22 +/- 10% by functioning as a mechanical barrier. When tPA was released from the hydrogel, adhesion formation was reduced to 4 +/- 3%, while when tPA was given by intraperitoneal injection, adhesion formation was only reduced to 49 +/- 8%. Local delivery of urokinase reduced adhesion formation to 6 +/- 6%, but intraperitoneal injection of urokinase did not reduce adhesion formation. Streptokinase did not reduce adhesion formation when administered by intraperitoneal injection and increased adhesion formation to 45 +/- 9% when locally released relative to the hydrogel alone. These results suggest that both tPA and uPA may be used to prevent adhesion formation when delivered locally.
Department of Biomedical and Chemical Engineering, University of Texas, Austin 78712, USA.
J L
JL
Hill-West
R C
RC
Dunn
J A
JA
Hubbell
D000818:Animals; D004343:Drug Implants; D005260:Female; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007274:Injections, Intraperitoneal; D011092:Polyethylene Glycols; D011183:Postoperative Complications / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013300:Streptokinase / Q000008:administration & dosage* / Q000494:pharmacology; D000267:Tissue Adhesions / Q000517:prevention & control; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage* / Q000494:pharmacology; D014591:Uterine Diseases / Q000517:prevention & control*; D014599:Uterus / Q000601:surgery*
D004343:Drug Implants; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D013300:Streptokinase; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator