Adhesion prevention with ancrod released via a tissue-adherent hydrogel.
The objective of this investigation was to evaluate the effect of ancrod, a fibrinogenolytic protease from Malayan pit viper venom, locally delivered through a photopolymerized biodegradable hydrogel in preventing postoperative adhesions. The experimental model involved ischemic and serosal injury to the uterine horns of rats with measurement of adhesions 7 days after injury. Ancrod was delivered intravenously for 5 days preoperatively through 3 days postoperatively, intraperitoneally for 5 days preoperatively, intraperitoneally for 3 days postoperatively, and locally via the hydrogel formed upon the uterine horns by photopolymerization of an aqueous precursor solution. Systemic defibrinogenation by intravenous administration pre-through postoperatively reduced the extent of adhesions by 63% without dose sensitivity from 5 to 20 units/kg/day. Preoperative defibrinogenation by intraperitoneal administration reduced adhesion extent by up to 57%, while postoperative administration was more effective, reducing adhesions by up to 84% with a dose-dependent response from 5 to 20 units/kg/day. Administration of ancrod by local release from a tissue-adherent hydrogel was more effective than either the hydrogel alone or the same amount of ancrod administered by postoperative intraperitoneal injection. Adhesions were reduced by 82% at a local dose of 10 units/kg, compared to a reduction of 68% due to the barrier properties of the gel alone (P < 0.01) and of 19% due to the same amount of drug given at the time of surgery (P < 0.001). Local delivery of ancrod from a tissue-adherent hydrogel barrier thus provided an efficacious prevention to postoperative adhesions while permitting administration of a low total dose of the protease.
Chowdhury
S M
SM
Department of Chemical Engineering, University of Texas, Austin 78712, USA.
Hubbell
J A
JA
D000005:Abdomen / Q000601:surgery; D000721:Ancrod / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007274:Injections, Intraperitoneal; D007511:Ischemia / Q000150:complications; D011092:Polyethylene Glycols; D011182:Postoperative Care; D011183:Postoperative Complications / Q000517:prevention & control*; D011300:Preoperative Care; D051381:Rats; D017207:Rats, Sprague-Dawley; D000267:Tissue Adhesions / Q000209:etiology / Q000517:prevention & control*; D014014:Tissue Adhesives; D014599:Uterus / Q000098:blood supply / Q000293:injuries; D014947:Wounds and Injuries / Q000150:complications
D005343:Fibrinolytic Agents; D014014:Tissue Adhesives; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D000721:Ancrod