Design of Biopolymer-Based Interstitial Therapies for the Treatment of Glioblastoma

Glioblastoma multiforme (GBM) is a highly aggressive brain cancer with a poor 5-year survival rate of approximately 5.6%. The standard of care—surgical resection followed by radiation and chemotherapy—is frequently undermined by the tumor's invasive nature and the blood-brain barrier (BBB), which limits the efficacy of systemic drugs. Interstitial therapy addresses these challenges by delivering chemotherapeutics directly into the resection cavity, bypassing the BBB and minimizing systemic toxicity.

Interstitial therapy typically involves implanting a drug-loaded, biodegradable polymer directly into the brain during tumor resection. This approach allows for sustained, local drug release as the polymer degrades, maintaining therapeutic concentrations at the site where recurrence is most likely. The primary advantage is the ability to tailor the release profile to the specific needs of the patient or the drug, potentially overcoming drug resistance and improving therapeutic indices.

Gliadel, the only FDA-approved interstitial therapy for GBM, consists of carmustine (BCNU) loaded into a polyanhydride wafer. While it has demonstrated clinical benefits, its impact remains modest due to factors such as rapid drug clearance, the development of drug resistance, and a release rate that was not fully optimized for maximum efficacy. The authors emphasize that future advancements require a more sophisticated understanding of how polymer degradation—whether through surface or bulk erosion—interacts with drug physicochemical properties.

To improve outcomes, research is shifting toward patient-specific combination therapies. Designing the next generation of implants requires careful selection of polymers that are biocompatible, biodegradable into non-toxic metabolites, and capable of providing controlled, sustained release. The authors argue that the future of GBM treatment lies in developing a library of devices where the polymer, drug, and formulation method are rationally engineered to address the high intratumoral heterogeneity of glioblastoma.