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Injectable Hydrogels for Localized Chemotherapy and Radiotherapy in Brain Tumors
Pilar de la Puente1, Nicole Fettig2, Micah J Luderer1
1Department of Radiation Oncology, Washington University in Saint Louis School of Medicine, St. Louis, Missouri 63110.
Abstract:
Overall survival of patients with newly diagnosed glioblastoma (GBM) remains dismal at 16 months with state-of-the-art treatment that includes surgical resection, radiation, and chemotherapy. GBM tumors are highly heterogeneous, and mechanisms for overcoming tumor resistance have not yet fully been elucidated. An injectable chitosan hydrogel capable of releasing chemotherapy (temozolomide [TMZ]) while retaining radioactive isotopes agents (iodine, [131I]) was used as a vehicle for localized radiation and chemotherapy, within the surgical cavity. Release from hydrogels loaded with TMZ or 131I was characterized in vitro and in vivo and their efficacy on tumor progression and survival on GBM tumors was also measured. The in vitro release of 131I was negligible over 42 days, whereas the TMZ was completely released over the first 48 h. 131I was completely retained in the tumor bed with negligible distribution in other tissues and that when delivered locally, the chemotherapy accumulated in the tumor at 10-fold higher concentrations than when delivered systemically. We found that the tumors were significantly decreased, and survival was improved in both treatment groups compared to the control group. Novel injectable chemo-radio-hydrogel implants may potentially improve the local control and overall outcome of aggressive, poor prognosis brain tumors.
Insights
Injectable hydrogels delivering localized chemotherapy (temozolomide) and radiation (iodine-131) improved survival in glioblastoma models. This novel approach offers a promising strategy for treating aggressive brain tumors.
Area of Science:
- Biomedical Engineering
- Oncology
- Materials Science
Background:
- Glioblastoma (GBM) has a poor prognosis with current treatments.
- Tumor heterogeneity and resistance mechanisms limit therapeutic efficacy.
- Localized drug and radiation delivery can improve treatment outcomes.
Purpose of the Study:
- To develop and evaluate an injectable chitosan hydrogel for localized delivery of chemotherapy and radiotherapy.
- To assess the in vitro and in vivo release kinetics and efficacy of the chemo-radio-hydrogel in GBM models.
Main Methods:
- An injectable chitosan hydrogel was formulated to co-deliver temozolomide (TMZ) and iodine-131 (131I).
- In vitro and in vivo release studies were performed to characterize drug and isotope release.
- Efficacy was evaluated by measuring tumor progression and overall survival in GBM-bearing animal models.
Main Results:
- The hydrogel demonstrated sustained release of TMZ over 48 hours and negligible release of 131I over 42 days.
- 131I was retained within the tumor bed with minimal systemic distribution.
- Local delivery resulted in 10-fold higher chemotherapy concentration in the tumor compared to systemic delivery.
- Both chemo-hydrogel and radio-hydrogel treatments significantly reduced tumor size and improved survival compared to controls.
Conclusions:
- Injectable chemo-radio-hydrogel implants are effective for localized treatment of GBM.
- This approach enhances local tumor control and improves survival outcomes for aggressive brain tumors.
