The composite gel can be injected directly into the postresection cavity after tumor bulk excision to achieve local drug delivery. The tissue adhesive property of the gel makes it more adaptable to the surgical cavity and capable of delivering the therapeutic agents to the infiltrative glioma tissue.
High-grade gliomas are aggressive brain tumors with poor prognosis, largely because even after surgical removal, infiltrative residual tumor cells often regrow during the latency before radiotherapy, leading to recurrence. The standard chemoradiotherapy only modestly improves survival. A crucial window of vulnerability arises post‑surgery, before radiotherapy begins, where residual tumor cells are not well addressed by systemic chemotherapy.
Prof. Feng-Huei Lin and Dr. Jason Lin from National Taiwan University have designed a local post‑surgical gel packing with sequential delivery of platinum agents that could maintain therapeutic drug concentrations intracranially and synergize with subsequent radiotherapy to eliminate glioma tissue. The study is published in Chemical Engineering Journal.
Novel Drug Delivery Gel for Glioma Treatment
A cutting-edge drug-delivery gel has been developed that can be directly injected into the surgical cavity following tumor resection. This gel provides sustained local delivery of platinum-based anticancer agents, ensuring effective eradication for residual glioma tissue that remain after surgery. The gel is designed to maximize the therapeutic impact while minimizing systemic exposure.
Sequential Platinum Delivery System
The gel utilizes a sequential delivery system to maximize its effectiveness. The first stage involves the immediate release of carboplatin, a platinum-based chemotherapy drug, which suppresses remaining glioma cells right after surgery. The second stage involves platinum-doped calcium carbonate (CaCO₃:Pt) particles, which release platinum agents more gradually. This delayed release occurs intracellularly through endocytosis, ensuring that the therapeutic effect continues over time before subsequent radiotherapy.
Composite Gel Induces Glioma Cell Death via DNA Damage
It was demonstrated that the gel induces significant apoptosis in glioma cells by causing substantial DNA damage (DNA double strand break), which is the critical mechanism for combating cancer.
When tested in orthotopic brain tumor models, where tumors are implanted directly into the brain, the gel, combined with radiotherapy, significantly suppressed tumor relapse. This combination treatment approach enhances the efficacy of radiotherapy while ensuring that the chemotherapy agents are delivered directly to the tumor site.
Reducing Radiation Dose While Enhancing Effectiveness
One of the most promising aspects of this composite gel is its ability to reduce the required dose of radiotherapy. By enhancing the local effectiveness of the chemotherapy and improving the sensitivity of tumor cells to radiation, the gel allows for the use of lower doses of radiotherapy.
Research scientist Dr. Jason Lin from Department of Biomedical Engineering, National Taiwan University, the study’s first author, said, “This approach not only boosts treatment efficacy but also minimizes the side effects associated with higher doses of radiation, ultimately leading to a safer and more effective treatment regimen.”
Principal investigator Prof. Feng-Huei Lin from Department of Biomedical Engineering, National Taiwan University, said, “Our findings show that the postoperatively injected gel, designed for sequential delivery of platinum-based agents, can significantly enhance radiotherapy outcomes and effectively reduce the risk of high-grade glioma relapse.”
Prof. Feng-Huei Lin's email address: [email protected]
