title: Temozolomide-loaded photopolymerizable PEG-DMA-based hydrogel for the treatment of glioblastoma.
abstract: Glioblastoma is the most frequent primary malignant brain tumor in adults. Despite treatments including surgery, radiotherapy and chemotherapy by oral Temozolomide (TMZ), the prognosis of patients with glioblastoma remains very poor. We hypothesized that a polyethylene glycol dimethacrylate (PEG-DMA) injectable hydrogel would provide a sustained and local delivery of TMZ. The hydrogel photopolymerized rapidly (<2min) and presented a viscous modulus (≈10kPa). TMZ release kinetic presented two phases: a linear burst release of 45% of TMZ during the first 24h, followed by a logarithmic release of 20% over the first week. The in vivo tolerability study showed that the unloaded hydrogel did not induce apoptosis in mice brains nor increased microglial activation. In vivo, the anti-tumor efficacy of TMZ-hydrogel was evaluated on xenograft U87MG tumor-bearing nude mice. The tumor weight of mice treated with the photopolymerized TMZ hydrogel drastically decreased compared with all other groups. Higher apoptosis (located at the center of the tumor) was also observed. The present study demonstrates the potential of a photopolymerizable TMZ-loaded hydrogel to treat glioblastoma.
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier, 73, B1 73.12, 1200 Brussels, Belgium.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Fourniols
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier, 73, B1 73.12, 1200 Brussels, Belgium.
authors.forename: Luc D
authors.initials: LD
authors.lastname: Randolph
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier, 73, B1 73.12, 1200 Brussels, Belgium.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Staub
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier, 73, B1 73.12, 1200 Brussels, Belgium.
authors.forename: Kevin
authors.initials: K
authors.lastname: Vanvarenberg
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier, 73, B1 73.12, 1200 Brussels, Belgium.
authors.forename: Julian G
authors.initials: JG
authors.lastname: Leprince
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier, 73, B1 73.12, 1200 Brussels, Belgium.
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier, 73, B1 73.12, 1200 Brussels, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: des Rieux
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier, 73, B1 73.12, 1200 Brussels, Belgium. Electronic address: fabienne.danhier@uclouvain.be.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Danhier
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000528:radiation effects / Q000627:therapeutic use; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000528:radiation effects / Q000627:therapeutic use; D016503:Drug Delivery Systems; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects / Q000627:therapeutic use; D008027:Light; D008689:Methacrylates / Q000737:chemistry / Q000528:radiation effects; D008819:Mice, Nude; D017628:Microglia / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry / Q000528:radiation effects; D000077204:Temozolomide; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003692:Delayed-Action Preparations; D020100:Hydrogels; D008689:Methacrylates; C421283:poly(ethylene glycol)-dimethacrylate; D011092:Polyethylene Glycols; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Glioblastoma; PEG-DMA; Photopolymerizable hydrogel; Polymeric micelles; Temozolomide