INTRODUCTION: Chemotherapeutic drug-eluting beads (DEBs) are microspheres that are in clinical use for intraarterial chemoembolisation of liver cancer. Here we report on the biocompatibility and anti-tumour efficacy of DEBs after intratumoral application in a rat BT4Ca glioma model. METHODS AND RESULTS: Doxorubicin and irinotecan-eluting DEBs were suspended in a Ca(2+)-free aqueous alginate solution that provides a sol-gel transition when injected into the Ca(2+) rich brain tissue. In this way the DEBs are immobilised at the implantation site. Forced elution studies in vitro using a USP-4 flow-through apparatus demonstrated that the alginate excipient helped to reduce the burst effect and rate the elution from the beads. From the in vivo evaluation, doxorubicin DEBs demonstrated a significant local toxicity, while irinotecan-loaded DEBs showed good local tissue compatibility. Doxorubicin at higher concentrations and irinotecan-loaded DEBs were found to decrease tumour volume, increase survival time and decrease the Ki67 proliferation index of the tumour. Doxorubicin was shown by fluorescent microscopy to diffuse into the peritumoral tissue, but also penetrates along white matter tracts, to more distant areas. DISCUSSION: We conclude that the alginate suspension of irinotecan DEBs can be considered safe and effective in a clinical setting.
INTRODUCTION: Chemotherapeutic drug-eluting beads (DEBs) are microspheres that are in clinical use for intraarterial chemoembolisation of liver cancer. Here we report on the biocompatibility and anti-tumour efficacy of DEBs after intratumoral application in a rat BT4Ca glioma model. METHODS AND RESULTS:Doxorubicin and irinotecan-eluting DEBs were suspended in a Ca(2+)-free aqueous alginate solution that provides a sol-gel transition when injected into the Ca(2+) rich brain tissue. In this way the DEBs are immobilised at the implantation site. Forced elution studies in vitro using a USP-4 flow-through apparatus demonstrated that the alginate excipient helped to reduce the burst effect and rate the elution from the beads. From the in vivo evaluation, doxorubicinDEBs demonstrated a significant local toxicity, while irinotecan-loaded DEBs showed good local tissue compatibility. Doxorubicin at higher concentrations and irinotecan-loaded DEBs were found to decrease tumour volume, increase survival time and decrease the Ki67 proliferation index of the tumour. Doxorubicin was shown by fluorescent microscopy to diffuse into the peritumoral tissue, but also penetrates along white matter tracts, to more distant areas. DISCUSSION: We conclude that the alginate suspension of irinotecan DEBs can be considered safe and effective in a clinical setting.
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