Fibrin glue as a local drug and photosensitizer delivery system for photochemical internalization: Potential for bypassing the blood-brain barrier.

Abstract

Chemotherapy has had disappointing results in the treatment of glioblastoma multiforme (GBM). This is in part due to limited systemic drug penetration through the blood-brain barrier. This limitation can be overcome by implantation of drug-loaded hydrogels, such as fibrin glue (FG), directly into the tumor resection cavity. Photochemical internalization (PCI) has been shown to enhance the efficacy of a large number of chemotherapeutic agents, including bleomycin (BLM). This study examined the ability of loaded FG to release BLM and photosensitizer to enable PCI-induced growth inhibition of glioma spheroids in vitro. FG layers, loaded with drug and photosensitizer, were formed in wells of a 24-well plate. Supernatants covering the FG layers were harvested after 48h. F98 glioma spheroids were co-incubated with harvested supernatants for 24h, followed by light exposure. Spheroid growth was monitored for an additional 14 days. 100% of the drug bleomycin and 90% of the photosensitizer (AlPcS2a) was released from the FG over a 48h interval. Spheroid growth was significantly inhibited or completely suppressed by PCI of released drug and photosensitizer in many of the concentration combinations tested. PCI-induced growth inhibition increased with increasing light levels. The results demonstrate that both drug and photosensitizer were loaded into and released in a non-degraded form for an extended time period. The growth inhibition caused by FG-released BLM was significantly enhanced by FG-released AlPcS2a-mediated PCI.