Blood-brain barrier (BBB) toxicity and permeability assessment after L-(4-¹⁰Boronophenyl)alanine, a conventional B-containing drug for boron neutron capture therapy, using an in vitro BBB model.
Since brain tumours are the primary candidates for treatment by Boron Neutron Capture Therapy, one major challenge in the selective drug delivery to CNS is the crossing of the blood-brain barrier (BBB). The present pilot study investigated (i) the transport of a conventional B-containing product (i.e., L-(4-(10)Boronophenyl)alanine, L-(10)BPA), already used in medicine but still not fully characterized regarding its CNS interactions, as well as (ii) the effects of the L-(10)BPA on the BBB integrity using an in vitro model, consisting of brain capillary endothelial cells co-cultured with glial cells, closely mimicking the in vivo conditions. The multi-step experimental strategy (i.e. Integrity test, Filter study, Transport assay) checked L-(10)BPA toxicity at 80 µg Boron equivalent/ml, and its ability to cross the BBB, additionally by characterizing the cytoskeletal and TJ's proteins by immunocytochemistry and immunoblotting. In conclusion, a lack of toxic effects of L-(10)BPA was demonstrated, nevertheless accompanied by cellular stress phenomena (e.g. vimentin expression modification), paralleled by a low permeability coefficient (0.39 ± 0.01 × 10(-3)cm min(-1)), corroborating the scarce probability that L-(10)BPA would reach therapeutically effective cerebral concentration. These findings emphasized the need for novel strategies aimed at optimizing boron delivery to brain tumours, trying to ameliorate the compound uptake or developing new targeted products suitable to safely and effectively treat head cancer. Thus, the use of in vitro BBB model for screening studies may provide a useful early safety assessment for new effective compounds.
['Roda|E|E|', 'Nion|S|S|', 'Bernocchi|G|G|', 'Coccini|T|T|']
D000818:Animals D001812:Blood-Brain Barrier D001895:Boron D001896:Boron Compounds D001921:Brain D002199:Capillary Permeability D002417:Cattle D018920:Coculture Techniques D003599:Cytoskeleton D042783:Endothelial Cells D009457:Neuroglia D062793:Occludin D010649:Phenylalanine D010865:Pilot Projects D051381:Rats D019108:Tight Junctions D014746:Vimentin D062826:Zonula Occludens-1 Protein
In vitro Screening study Central nervous system Head tumours