title: Site-specific delivery of dexamethasone from biodegradable implants reduces formation of pericardial adhesions in rabbits.
abstract: Repeated sternotomy often leads to serious complications in patients due to the formation of cardiac adhesions. In this study we characterized dexamethasone-loaded biodegradable poly(lactide)-poly(ethyleneglycol) copolymer films for site-specific drug delivery and examined their efficacy in the rabbit model of postoperative cardiac adhesions. Tritiated dexamethasone-loaded films were used to determine the in vitro release and in vivo drug distribution. Dexamethasone release in serum was biphasic with 69% drug released after 72 hr. The implants produced sustained drug levels at the implantation site with low distribution into the peripheral tissues. The matrices were implanted in rabbits between the epicardium and the sternum following sternotomy, pericardiectomy and epicardium abrasion, with the drug-releasing surface facing the epicardium. The tenacity and density of the adhesions was examined 21 days post procedure in comparison to both groups of untreated and rabbits implanted with blank matrices. Similarly tenacious and dense adhesions were observed in both control groups. In contrast, epicardial adhesions' formation was significantly reduced and the anatomy was preserved in the treated animals. It is concluded that local delivery of dexamethasone from biodegradable implants provides a promising approach for the prevention of pericardial adhesions while potentially minimizing the systemic adverse effects inherent to systemic therapy or high blood levels of the drug.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. chorny@email.chop.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Chorny
authors.forename: David
authors.initials: D
authors.lastname: Mishaly
authors.forename: Avshalom
authors.initials: A
authors.lastname: Leibowitz
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Domb
authors.forename: Gershon
authors.initials: G
authors.lastname: Golomb
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004343:Drug Implants; D023421:Models, Animal; D010490:Pericardial Effusion / Q000517:prevention & control*; D010496:Pericardium / Q000601:surgery; D011091:Polyesters; D011092:Polyethylene Glycols; D011183:Postoperative Complications; D011817:Rabbits; D000267:Tissue Adhesions / Q000517:prevention & control
chemical_list: D001672:Biocompatible Materials; D004343:Drug Implants; D011091:Polyesters; C507889:polylactide-polyethylene glycol-polylactide; D011092:Polyethylene Glycols; D003907:Dexamethasone