Hydrogel-mediated delivery of chemotherapeutic agents to the brain after tumour resection

Glioblastoma recurrence poses a substantial challenge in clinical treatment. One promising strategy involves the use of injectable hydrogels loaded with chemotherapeutic agents, which can be applied directly to the post-surgical resection cavity to enable sustained drug release targeting residual tumour cells that evade initial interventions. However, the therapeutic efficacy of this approach remains constrained, primarily due to a lack of understanding of optimal drug selection and the underlying transport mechanisms. In this study, a mathematical modelling framework is employed to evaluate the transport dynamics and accumulation profiles of seven chemotherapeutic agents, including fluorouracil, temozolomide, carmustine, cisplatin, methotrexate, doxorubicin, and paclitaxel. Simulations are conducted using a 3D postoperative brain geometry reconstructed from patient magnetic resonance imaging data. The results reveal that paclitaxel exhibits continuous accumulation in brain tissue over the course of a week, whereas the other agents are substantially reduced within the same timeframe. Drug transport is primarily influenced by elimination mechanisms, including bioreaction, physical degradation, and clearance via blood drainage, followed by interstitial diffusion and convection driven by interstitial fluid flow. Among the evaluated agents, methotrexate and temozolomide demonstrate a wider distribution during the early phase, despite their concentrations declining rapidly thereafter. In contrast, cisplatin demonstrates a relatively slower temporal response in transport. This results in a more gradual reduction in its coverage following peak distribution, thereby allowing it to maintain therapeutic efficacy over time. Paclitaxel, on the other hand, displays a continuously expanding spatial distribution throughout the observation period and achieves the highest cumulative drug exposure. These findings provide valuable insights to inform the selection of chemotherapeutic agents and the optimisation of hydrogel-based delivery systems for improving treatment efficacy and reducing the likelihood of glioblastoma recurrence.