title: Tunable delivery of niflumic acid from resorbable embolization microspheres for uterine fibroid embolization.
abstract: Uterine arteries embolization (UAE) is a recent technique that aims, by means of particles injected percutaneously, to stifle fibroids (leiomyomas). This treatment is non-invasive, compared with uterine ablation, but generates pelvic pain for a few days. A strategy to reduce the post-embolization pain would be to use calibrated embolization microspheres preloaded with a non-steroidal inflammatory drug (NSAID). In this study, we first compared four drugs, all active at low concentration on cyclooxygenase-2, i.e. ketoprofen, sodium diclofenac, flurbiprofen and niflumic acid (NFA), for their capacity to be loaded on resorbable embolization microspheres (REM) 500-700μm. NFA had the highest capacity of loading (5mg/mL) on resorbable microspheres. Then, we evaluated in vitro the NFA release profiles from REM having various degradation times of one, two or five days. NFA release was biphasic, with an initial burst (about 60% of the loading) followed by a sustained release that correlated significantly to REM's hydrolysis (rho=0.761, p<0.0001). For each group of beads, the size distribution was not modified by the loading of NFA and their delivery through microcatheter was not impaired by the drug. NFA eluted from REM inhibited the synthesis of prostaglandin E2 from rabbit uterus explants. In summary, NFA is loadable on REM in significant amount and its delivery can be tuned according to the degradation rate of REM to provide an antalgic effect for a few days after UAE.
authors.affiliation: Occlugel S.A.S., 12 Rue Charles de Gaulle, 78350 Jouy en Josas, France. Electronic address: l.bedouet@hotmail.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bédouet
authors.affiliation: Université Paris-Sud, Institut Galien Paris-Sud, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France; CNRS UMR 8612, Institut Galien Paris-Sud, LabEx LERMIT, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Moine
authors.affiliation: Occlugel S.A.S., 12 Rue Charles de Gaulle, 78350 Jouy en Josas, France.
authors.forename: Emeline
authors.initials: E
authors.lastname: Servais
authors.affiliation: Occlugel S.A.S., 12 Rue Charles de Gaulle, 78350 Jouy en Josas, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Beilvert
authors.affiliation: Université Paris-Sud, Institut Galien Paris-Sud, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France; CNRS UMR 8612, Institut Galien Paris-Sud, LabEx LERMIT, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Labarre
authors.affiliation: Assistance Publique Hôpitaux de Paris ⿿ Hôpital Lariboisière, Département de Neuroradiologie, 2rue Ambroise Paré, 75010 Paris, France; CNRS UMR 7057, Laboratoire Matières et Systèmes Complexes, Université Paris 7, 10 rue Alice Domon et Léonie Duquet, 75205 Paris Cedex 13, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Laurent
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D005260:Female; D007889:Leiomyoma / Q000378:metabolism / Q000628:therapy; D008863:Microspheres; D009544:Niflumic Acid / Q000008:administration & dosage*; D011817:Rabbits; D055357:Uterine Artery Embolization / Q000379:methods*; D014594:Uterine Neoplasms / Q000378:metabolism / Q000628:therapy; D014599:Uterus / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism
chemical_list: D009544:Niflumic Acid
keywords: Embolization; Fibroid; Microsphere; NSAIDs; Niflumic acid; Resorbable