title: Poly(ethylene glycol) methacrylate hydrolyzable microspheres for transient vascular embolization.
abstract: Poly(ethylene glycol) methacrylate (PEGMA) hydrolyzable microspheres intended for biomedical applications were readily prepared from poly(lactide-co-glycolide) (PLGA)-poly(ethylene glycol) (PEG)-PLGA crosslinker and PEGMA as a monomer using a suspension polymerization process. Additional co-monomers, methacrylic acid and 2-methylene-1,3-dioxepane (MDO), were incorporated into the initial formulation to improve the properties of the microspheres. All synthesized microspheres were spherical in shape, calibrated in the 300-500 μm range, swelled in phosphate-buffered saline (PBS) and easily injectable through a microcatheter. Hydrolytic degradation experiments performed in PBS at 37 °C showed that all of the formulations tested were totally degraded in less than 2 days. The resulting degradation products were a mixture of low-molecular-weight compounds (PEG, lactic and glycolic acids) and water-soluble polymethacrylate chains having molecular weights below the threshold for renal filtration of 50 kg mol(-1) for the microspheres containing MDO. Both the microspheres and the degradation products were determined to exhibit minimal cytotoxicity against L929 fibroblasts. Additionally, in vivo implantation in a subcutaneous rabbit model supported the in vitro results of a rapid degradation rate of microspheres and provided only a mild and transient inflammatory reaction comparable to that of the control group.
authors: Occlugel S.A.S., 12 Rue Charles de Gaulle, 78350 Jouy en Josas, France.
authors: Stéphanie
authors: S
authors: Louguet
authors: 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: Valentin
authors: V
authors: Verret
authors: Occlugel S.A.S., 12 Rue Charles de Gaulle, 78350 Jouy en Josas, France.
authors: Laurent
authors: L
authors: Bédouet
authors: Occlugel S.A.S., 12 Rue Charles de Gaulle, 78350 Jouy en Josas, France.
authors: Emeline
authors: E
authors: Servais
authors: Archimmed S.A.R.L., 12 Rue Charles de Gaulle, 78350 Jouy en Josas, France.
authors: Florentina
authors: F
authors: Pascale
authors: AP-HP hôpital Lariboisière, Department of Pathology, University of Paris 7 - Denis Diderot, Faculty of Medicine, 2 rue Ambroise Paré, 75010 Paris, France.
authors: Michel
authors: M
authors: Wassef
authors: 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: Denis
authors: D
authors: Labarre
authors: AP-HP hôpital Lariboisière, Department of Pathology, University of Paris 7 - Denis Diderot, Faculty of Medicine, 2 rue Ambroise Paré, 75010 Paris, France; "Laboratoire Matières et Systèmes Complexes", CNRS 7057, University of Paris 7, Bâtiment Condorcet, 10 rue Alice Domon et Léonie Duquet, 75205 Paris Cedex 13, France.
authors: Alexandre
authors: A
authors: Laurent
authors: 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. Electronic address: laurence.moine@u-psud.fr.
authors: Laurence
authors: L
authors: Moine
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology; D004621:Embolization, Therapeutic; D006868:Hydrolysis; D020007:Implants, Experimental; D019344:Lactic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008689:Methacrylates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008863:Microspheres; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D017550:Spectroscopy, Fourier Transform Infrared; D040521:Subcutaneous Tissue / Q000187:drug effects
chemical_list: D008689:Methacrylates; C524499:polyethylene glycol methacrylate; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Degradable; Embolization; Hydrolyzable crosslinker; Microsphere; PEG-based hydrogel