title: Embolization biomaterial reinforced with nanotechnology for an in-situ release of anti-angiogenic agent in the treatment of hyper-vascularized tumors and arteriovenous malformations.
abstract: A polymer based material was developed to act as an embolic agent and drug reservoir for the treatment of arteriovenous malformations (AVM) and hyper vascularized solid tumors. The aim was to combine the blocking of blood supply to the target region and the inhibition of the embolization-stimulated angiogenesis. The material is composed of an ethanolic solution of a linear acrylate based copolymer and acrylate calibrated microparticles containing nanospheres loaded with sunitinib, an anti-angiogenic agent. The precipitation of the linear copolymer in aqueous environment after injection through microcatheter results in the formation of an in-situ embolization gel whereas the microparticles serve to increase the cohesive properties of the embolization agent and to form a reservoir from which the sunitinib-loaded nanospheres are released post-embolization. The swollen state of the microparticles in contact with aqueous medium results in the release of the nanospheres out of microparticles macromolecular structure. After the synthesis, the formulation and the characterization of the different components of the material, anti-angiogenic activity was evaluated in vitro using endothelial cells and in vivo using corneal neovascularization model in rabbit. The efficiency of the arterial embolization was tested in vivo in a sheep model. Results proved the feasibility of this new system for vascular embolization in association with an in situ delivery of anti-angiogenic drug. This combination is a promising strategy for the management of arteriovenous malformations and solid tumors.
authors.affiliation: Université Paris Sud, EA401, IFR 141-ITFM, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France. Electronic address: emile.jubeli@u-psud.fr.
authors.forename: E
authors.initials: E
authors.lastname: Jubeli
authors.affiliation: Université Paris Sud, EA401, IFR 141-ITFM, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France.
authors.forename: N
authors.initials: N
authors.lastname: Yagoubi
authors.affiliation: AP-HP and INRA, Center for Research of Interventional Imaging (CR2i), 78352 Jouy en Josas, France.
authors.forename: F
authors.initials: F
authors.lastname: Pascale
authors.affiliation: Occlugel, Archimed, 12 rue Charles de Gaulle, 78350 Jouy en Josas, France.
authors.forename: L
authors.initials: L
authors.lastname: Bédouet
authors.affiliation: Université Paris Sud, UMR CNRS 8612, IFR 141-ITFM, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France; AP-HP Hôpital Lariboisière, Department of Interventional Neuroradiology, 2 rue Ambroise Paré, 75475 Paris, France.
authors.forename: K
authors.initials: K
authors.lastname: Slimani
authors.affiliation: Université Paris Sud, UMR CNRS 8612, IFR 141-ITFM, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France.
authors.forename: D
authors.initials: D
authors.lastname: Labarre
authors.affiliation: AP-HP Hôpital Lariboisière, Department of Interventional Neuroradiology, 2 rue Ambroise Paré, 75475 Paris, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Saint-Maurice
authors.affiliation: AP-HP and INRA, Center for Research of Interventional Imaging (CR2i), 78352 Jouy en Josas, France; Occlugel, Archimed, 12 rue Charles de Gaulle, 78350 Jouy en Josas, France; AP-HP Hôpital Lariboisière, Department of Interventional Neuroradiology, 2 rue Ambroise Paré, 75475 Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Laurent
authors.affiliation: Université Paris Sud, UMR CNRS 8612, IFR 141-ITFM, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France.
authors.forename: L
authors.initials: L
authors.lastname: Moine
mesh_terms: D000179:Acrylates / Q000009:adverse effects / Q000737:chemistry; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001165:Arteriovenous Malformations / Q000188:drug therapy; D001672:Biocompatible Materials / Q000009:adverse effects / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003315:Cornea / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000009:adverse effects; D004621:Embolization, Therapeutic / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D005782:Gels; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D007366:Intercostal Muscles / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D054118:Nanospheres / Q000009:adverse effects / Q000737:chemistry*; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control*; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D011897:Random Allocation; D034561:Sheep, Domestic; D000077210:Sunitinib
chemical_list: D000179:Acrylates; D020533:Angiogenesis Inhibitors; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D005782:Gels; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: Anti-angiogenic; Arteriovenous malformation; Embolization; Gelling solution; Sunitinib