Concurrent delivery of carmustine, irinotecan, and cisplatin to the cerebral cavity using biodegradable nanofibers: In vitro and in vivo studies

• We developed biodegradable anti-cancer drug-eluting nanofibers.
• Nanofibers provided concurrent and sustained drug delivery to the cerebral cavity.
• Nanofibers released high concentrations of drugs for more than 8 weeks.
• Histological examination showed no inflammatory reactions of the brain tissues.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, and the prognosis of patients afflicted with GBM has been dismal, exhibiting progressive neurologic impairment and imminent death. Even with the most active regimens currently available, chemotherapy achieves only modest improvement in the overall survival. New chemotherapeutic agents and novel approaches to therapy are required for improving clinical outcomes. In this study, we used an electrospinning technique and developed biodegradable poly[(d,l)-lactide-co-glycolide] nanofibrous membranes that facilitated a sustained release of carmustine (or bis-chloroethylnitrosourea, BCNU), irinotecan, and cisplatin. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vitro and in vivo release behaviors of pharmaceuticals from the nanofibrous membranes. The experimental results showed that the biodegradable, nanofibrous membranes released high concentrations of BCNU, irinotecan, and cisplatin for more than 8 weeks in the cerebral cavity of rats. A histological examination revealed progressive atrophy of the brain tissues without inflammatory reactions. Biodegradable drug-eluting nanofibrous membranes may facilitate sustained delivery of various and concurrent chemotherapeutic agents in the cerebral cavity, enhancing the therapeutic efficacy of GBM treatment and preventing toxic effects resulting from the systemic administration of chemotherapeutic agents.

The multiple chemotherepeutic agents loaded nanofibrous membranes were implanted into the brain surface after craniectomy. A biodegradable PLGA nanofibrous membrane provided sustainably high concentrations of BCNU, irinotecan, and cisplatin in the brain tissue lasting more than 8 weeks. By contrast, the drug concentrations in the blood were extremely low. Gross wound appearances and pathologic examinations revealed no inflammation response and chemotherapy induced brain atrophy (decrease in cellularity).Figure optionsDownload as PowerPoint slide