Temozolomide and Carmustine biodegradable wafer for the treatment of brain cancer

Tovi Furman ¹ Riccardo Serra ² Awanish Kumar ¹ Henry Brem ^2,3,4 Betty Tyler ² Avi Domb ¹

¹Medicinal Chemistry, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel
²Department of Neurosurgery, Johns Hopkins University, Baltimore, USA
³Department of Oncology, Johns Hopkins University, Baltimore, USA
⁴Department of Biomedical Engineering, Johns Hopkins University, Baltimore, USA

Glioblastoma (GBM), the most aggressive and common brain tumor in adults, is uniquely resistant to therapies and is highly invasive. Requirements for local delivery of anti tumor therapeutics for extended time period should increase intratumoral concentration of cytotoxic agents and improve activity. A PLGA based wafers loaded with bis-chloroethylnitrosourea (BCNU) and temozolomide (TMZ) were prepared and tested in vivo.

Wafers were loaded with varying amount (%W/W) of the drugs in poly(lactic acid-co-glycolic acid) (PLGA). The drug loaded wafers showed a reliable in vitro release of a high dose of TMZ for a period of 4 weeks.

In vivo study in rats bearing brain tumors were treated with BCNU and TMZ loaded wafers resulted in a significant increase in median survival as compared to controls. No evidence of local or systemic toxicity was recorded.