DDEL-03. ASSESSING THE DEPTH OF DRUG PENETRATION INTO BRAIN PARENCHYMA FROM LOCAL DRUG DELIVERY SYSTEMS IN AN ORTHOTOPIC HIGH GRADE GLIOMA ALLOGRAFT USING ORBITRAP-SECONDARY ION MASS SPECTROMETRY

Abstract Local intracranial drug delivery for high-grade glioma has been developed over the last two decades with chemotherapeutic agents administered immediately adjuvant to neurosurgery overcome poor blood brain barrier permeability. In addition this, incorporation of nanoparticles (NPs) into local systems (DDS) can result in increased penetration chemotherapeutics through parenchyma, transporting further from administration site than by molecule diffusion alone.Here we adopted model DDS containing NPs compare depth parenchyma. Approach one consisted a thermosensitive situ assembling polymer matrix loaded polymer-doxorubicin conjugated which line resection cavity walls, while approach drug-loaded (etoposide and olaparib) poly(lactic acid)-poly(ethylene glycol) polymeric held within bioadhesive pectin hydrogel delivered via spray device.We assessed efficacy both at preventing recurrence an orthotopic rat 9L gliosarcoma following surgical resection. monitoring long-term survival, effect each was measured histologically H&E caspase-1 (inflammatory response) ki67 (cell proliferation) immunostaining staining. Depth evaluated on post-sacrificial sections using Orbitrap-Secondary Ion Mass Spectroscopy (OrbiSIMS) fluorescent microscopy. vivo data suggests that mechanism affects DDS, whereby survival observed rats treated sprayed olaparib/etoposide NP formulation, relative where simply pipetted cavity. OrbiSIMS confirmed presence doxorubicin, olaparib etoposide tissue. Our work encourages consideration mass spectrometry modalities complement studies, as analytical tool assess distribution systemically drugs, or localised drugs released biomaterial-based DDS.