Glioblastoma (GBM) is the most common primary brain tumor. Even with the current standard of care, which includes surgical resection, radiation, and chemotherapy, the median survival for GBM patients’ remains 12 - 15 months. Because approximately 90% of tumors recur within 2 cm of the original tumor, implanting drug loaded scaffolds after surgical resection remains a promising strategy to delay or prevent local GBM recurrence. The only FDA-approved polymer implant for interstitial drug delivery for GBM, Gliadel, has afforded minimal improvement in combatting GBM recurrence, in part due to its poor drug release profile. Here we explored the use of acetalated dextran (Ace-DEX), a polymer with tunable degradation rates, as a drug delivery platform for optimizing interstitial therapy to combat GBM. Ace-DEX scaffolds with wide range of drug release rates were fabricated by tuning parameters such as drug loading, solvent system, and Ace-DEX degradation rate. Scaffolds were then evaluated in two clinically relevant murine models of GBM: (1) GBM surgical resection and recurrence to replicate the positive tumor margins often left behind during surgery and (2) a contralateral hemisphere model, which allowed us to evaluate therapeutic effect of drug penetration to tumor deposits more distant from the resection cavity. We found that optimal release rate differed depending on tumor location. In the GBM model of resection and recurrence, a combination of scaffolds with fast and slow drug release rates resulted in significantly improved survival compared to individual release rates of fast and slow. However, in the contralateral hemisphere model, the fast drug releasing scaffold outperformed slow. These results highlight the substantial impact of scaffold parameters on therapeutic efficacy in interstitial GBM therapy.

Drug-loaded polymer scaffold parameters on treatment of postsurgical glioblastoma

2019 Fall National Meeting

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