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

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 (approximate to 10 kPa). TMZ release kinetic presented two phases: a linear burst release of 45% of TMZ during the first 24 h, 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 inmice brains nor increasedmicroglial activation. In vivo, the anti-tumor efficacy of TMZ-hydrogel was evaluated on xenograft U87MGtumor-bearing nude mice. The tumor weight of mice treated with the photopolymerized TMZ hydrogel drastically decreased comparedwith 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. (C) 2015 Elsevier B.V. All rights reserved.