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.
Hill-West
J L
JL
Department of Biomedical and Chemical Engineering, University of Texas, Austin 78712, USA.
Dunn
R C
RC
Hubbell
J A
JA
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