title: Anti-angiogenic drug delivery from hydrophilic resorbable embolization microspheres: an in vitro study with sunitinib and bevacizumab.
abstract: Anti-angiogenic (AA) drugs are proposed as novel agents for targeted therapies in hepatocellular carcinoma (HCC). Loading of AA drugs into drug delivery systems for local delivery would reduce their side effects. The present study investigated the loading and the delivery of two AA drugs, sunitinib and bevacizumab, from one day-resorbable embolization microspheres (REM). REM were prepared with 10 or 20% of methacrylic acid (MA) as active drug binding monomer. Sterilized beads (100-300 μm) were analyzed for cytotoxicity, AA loading and in vitro release. REM modified with MA were not cytotoxic and extemporaneous drug loading was significantly higher on REM containing 20% of MA. The drug release in saline buffer was sustained for several hours before complete REM degradation. MA content had low effect on drug release profile. When eluted from REM, sunitinib and bevacizumab reduced viability of tumoral VX2 cells, and proliferation of human endothelial cells, respectively. Deliverability of REM via microcatheter was not impaired by the loaded drugs. As conclusion, the loading values of sunitinib and bevacizumab on REM were close to those achieved for cytotoxic drugs onto non-degradable MS used in chemoembolization of HCC. Transcatheter delivery to liver tumors of anti-angiogenics could be achieved with REM.
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: Occlugel S.A.S., 12 Rue Charles de Gaulle, 78350 Jouy en Josas, France; ArchimMed S.A.R.L., 12 Rue Charles de Gaulle, 78350 Jouy en Josas, France.
authors.forename: Valentin
authors.initials: V
authors.lastname: Verret
authors.affiliation: Occlugel S.A.S., 12 Rue Charles de Gaulle, 78350 Jouy en Josas, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Louguet
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: ArchimMed S.A.R.L., 12 Rue Charles de Gaulle, 78350 Jouy en Josas, France.
authors.forename: Florentina
authors.initials: F
authors.lastname: Pascale
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: UPAC & C (Unité de préparation des anticancéreux et contrôle), Hôpital Saint-Antoine, Hôpitaux Universitaires Est Parisien, AP-HP, 184 Rue du Faubourg Saint-Antoine, 75012 Paris, France.
authors.forename: Minh-Tâm
authors.initials: MT
authors.lastname: Baylatry
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: 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: AP-HP hôpital Lariboisière, Department of Neuroradiology, Université Paris 7 - Denis Diderot, Faculté de medicine, 2 Rue Ambroise Paré, 75010 Paris, France; Laboratoire Matières et Systèmes Complexes, CNRS 7057, Université Paris 7, Bâtiment Condorcet, 10 Rue Alice Domon et Léonie Duquet, 75205 Paris Cedex 13, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Laurent
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002460:Cell Line; D016503:Drug Delivery Systems / Q000379:methods*; D004621:Embolization, Therapeutic / Q000379:methods*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007211:Indoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008863:Microspheres; D011758:Pyrroles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077210:Sunitinib; D014407:Tumor Cells, Cultured
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; D000068258:Bevacizumab; D000077210:Sunitinib
keywords: Bevacizumab; Chemoembolization; Drug delivery; Microspheres; Resorbable; Sunitinib