title: Release of ibuprofen from beads for embolization: in vitro and in vivo studies.
abstract: Ibuprofen (IBU) loaded polyvinyl alcohol-based hydrogel beads (IBU-BB) were designed to alleviate side effects such as inflammation and pain following uterine artery embolization for the treatment of leiomyomata. The present in vitro and in vivo study examines whether IBU-BB provide a sustained-release of the drug. In vitro release studies of IBU from IBU-BB (10, 50, 100 mg/mL), IBU solution (PEDEA) and IBU powder were compared using the T apparatus and the beaker method. The pharmacokinetic profile of IBU release was examined in vivo, following sheep uterine artery embolization with 100 mg/mL IBU-BB or after intra-arterial injection of IBU solution. IBU-BB can deliver high concentrations of the drug over time. The in vitro release from IBU-BB was markedly slower compared to IBU solution. Increasing the concentration of loaded IBU from 10 to 100 mg/mL decreased the rate of release. IBU release from the T apparatus was slower than the release in the beaker. In vivo, the release of the drug was progressive, without the early peak observed with IBU solution. A high level of correlation was obtained between in vivo and in vitro (T apparatus) results. Theoretically, IBU-BB could sustainably release high concentrations of IBU at the site of the uterine fibroids, which makes it a promising approach for the control of post-embolization pain.
authors.affiliation: Laboratoire Matière et Systèmes complexes, UMR CNRS 7057, Université Paris 7, 2, place Jussieu, 75006 Paris, France. Tatiana.borovac@brs.aphp.fr
authors.forename: T
authors.initials: T
authors.lastname: Borovac
authors.forename: J P
authors.initials: JP
authors.lastname: Pelage
authors.forename: A
authors.initials: A
authors.lastname: Kasselouri
authors.forename: P
authors.initials: P
authors.lastname: Prognon
authors.forename: G
authors.initials: G
authors.lastname: Guiffant
authors.forename: A
authors.initials: A
authors.lastname: Laurent
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D004621:Embolization, Therapeutic; D005069:Evaluation Studies as Topic; D005079:Excipients / Q000737:chemistry; D005260:Female; D007052:Ibuprofen / Q000737:chemistry / Q000493:pharmacokinetics*; D007700:Kinetics; D007889:Leiomyoma / Q000628:therapy; D008863:Microspheres; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011208:Powders; D012756:Sheep; D012995:Solubility; D012996:Solutions; D014599:Uterus / Q000098:blood supply*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D005079:Excipients; D011208:Powders; D012996:Solutions; C062364:polyvinyl alcohol hydrogel; D011142:Polyvinyl Alcohol; D007052:Ibuprofen