SCIDOT-25. ENHANCING THE EFFICACY OF DRUG RELEASED FROM LOADED FIBRIN GLUE BY PHOTOCHEMICAL INTERNALIZATION (PCI)

Although gross total resection of gliomas is often possible with current available techniques, almost all tumors recur due to the infiltrative nature of these tumors. Infiltrative tumor cells in normal brain are consequently protected by the blood brain barrier (BBB), greatly reducing the efficacy of chemotherapy. Localized per-operative methods of slow-release drug delivery, that bypass the BBB altogether, are therefore of considerable interest. Fibrin glue (FG) is a FDA approved compound often used during surgery. FG loaded with drugs has been studied as a localized controlled release vehicle but the quantity and release kinetics attainable for some drugs using FG are often inadequate. Photochemical internalization (PCI) has been demonstrated to significantly enhance the efficacy of several chemo-theraputic agents such as bleomycin (BLM) and doxorubicin (DOX). In particular PCI of BLM has been shown to be effective in sterilizing the tumor bed after marginal cytoreductive surgery. We have evaluated the ability of PCI to enhance the ability of BLM and DOX, released from loaded FG, to inhibit the growth of multi-cell glioma spheroids in vitro. Spheroid growth was monitored for 14 days. The results of the present study show that drug was released for up to 72 hours. The growth inhibition caused by either BLM or DOX was significantly enhanced by PCI. The photosensitizer AlPcS2a could also be loaded and released from FG allowing local delivery at the tumor site.