en
Scientific article
English

Temozolomide-loaded photopolymerizable PEG-DMA-based hydrogel for the treatment of glioblastoma

Published inJournal of controlled release, vol. 210, p. 95-104
Publication date2015-07-28
First online date2015-05-15
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.

eng
Keywords
  • Glioblastoma
  • PEG-DMA
  • Photopolymerizable hydrogel
  • Polymeric micelles
  • Temozolomide
  • Animals
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / chemistry
  • Antineoplastic Agents, Alkylating / radiation effects
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Apoptosis / drug effects
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dacarbazine / administration & dosage
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / chemistry
  • Dacarbazine / radiation effects
  • Dacarbazine / therapeutic use
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / radiation effects
  • Delayed-Action Preparations / therapeutic use
  • Drug Delivery Systems
  • Female
  • Glioblastoma / drug therapy
  • Glioblastoma / pathology
  • Humans
  • Hydrogels / administration & dosage
  • Hydrogels / chemistry
  • Hydrogels / radiation effects
  • Hydrogels / therapeutic use
  • Light
  • Methacrylates / chemistry
  • Methacrylates / radiation effects
  • Mice, Nude
  • Microglia / drug effects
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / radiation effects
  • Tumor Burden / drug effects
Affiliation Not a UNIGE publication
Citation (ISO format)
FOURNIOLS, Thibaut et al. Temozolomide-loaded photopolymerizable PEG-DMA-based hydrogel for the treatment of glioblastoma. In: Journal of controlled release, 2015, vol. 210, p. 95–104. doi: 10.1016/j.jconrel.2015.05.272
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Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal0168-3659
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