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Targeting anticancer drugs to the brain. I: Enhanced brain delivery of oxantrazole following administration in magnetic cationic microspheres.

A magnetic cationic microsphere delivery system, prepared from the polysaccharide chitosan and containing oxantrazole (OX), was examined for its ability to enhance brain delivery of OX compared to administration of OX in solution (OX-S). Magnetic chitosan microspheres containing OX (MCM-OX) and OX-S were administered intraarterially to male Fischer 344 rats at OX doses of 0.1 mg/kg and 0.5 mg/kg with a magnetic field of 6000 G applied to the brain for 30 min. Animals were sacrificed at 30 min and 120 min after MCM-OX and OX-S treatments, and multiple tissues were collected and analyzed for OX by HPLC. A statistical analysis of the effects of treatment, OX dose, and time on total OX in each sampled tissue was made. MCM-OX significantly increased OX brain concentrations compared to those achieved with OX-S treatments, concentrations after MCM-OX being a minimum of 100-fold greater. Within the MCM-OX treatment groups, ipsilateral OX concentrations were much greater, indicating target organ selectivity. A most interesting finding was that OX brain concentrations were similar at 120 min and 30 min after MCM-OX treatment. Thus, even in the absence of the magnetic field, MCM-OX were retained in the brain, possibly through cationic-anionic interactions with the blood-brain barrier.