Concurrent and Sequential Chemotherapy of Glioblastoma Multiforme in Rats Using Biodegradable Drug-Eluting Nanofibers

Glioblastoma multiforme (GBM) is the most common and most aggressive malignant primary brain tumor in humans, and the prognosis of the patients afflicted with these tumors has been historically dismal, with progressive neurologic impairment and imminent death. Standard treatment consists of maximal surgical resection, radiotherapy, and concomitant and adjuvant chemotherapy. Despite 30 years of intensive efforts to find an effective chemotherapy regimen for GBM. In the first step, the biodegradable drug-eluting nanofibrous membrane will be implanted into the cerebral cavity of rat after craniectomy. In the concurrent group, the 50:50 PLGA membrane embedded three chemotherapy agents (Carmustin, Cisplantin and Irinotectan). And in the sequential group, 50:50 PLGA is embedded three chemotherapy agents (Carmustin, Cisplantin and Irinotectan) and added 75:25 PLGA is embedded anti-angiogenesis agent (Combrestatin). An eluting method and HPLC assay were employed to characterize the iv vitro and in vivo release behaviors of pharmaceuticals from the nanofibrous membrane. In the second step, we will create glioblastoma multiforme in rat brain via implanting C6 gliomal cell. All the rats accepted pre-treatment MRI examination to make sure the tumor was created. In the group A, the PLGA nanomembrane without drug will be implanted into tumor-bearing brain of tumor-bearing rats. In the group B, PLGA nanomembrane embedded Carmustin, Cisplantin and Irinotectan will be implanted and PLGA embedded Carmustin, Cisplantin,Irinotectan and Combrestatin will be implanted in the group C. MRI examinations will be followed regularly to observed the tumor progression. Histological examinations will be performed to observe the growth of tumor cell. The results to evaluate the potential of nanofibrous membranes for the long-term deliveries of combined chemotherapy agents to treatment GBM clinically.