Pharmaceutical research · 2003
Evaluation of folate conjugate uptake and transport by the choroid plexus of mice.
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Kennedy Michael D, Jallad Karim N, Lu June, Low Philip S, Ben-Amotz Dor
Аннотация
PURPOSE: Because the choroid plexus (CP) is enriched in cell surface folate receptors, an investigation was initiated to evaluate whether folate receptor-mediated transcytosis might be exploited to deliver folate conjugates into the brain.
METHODS: Balb/c mice were injected with radioactive and fluorescent conjugates of folate to measure and image their uptake by the CP.
RESULTS: Retention of a radioactive folate conjugate, folate-diethylenetriaminepentaacetic acid (DTPA)-111In, into the brain of balb/c mice was observed, although repeated injections or prolonged release via an osmotic pump of the compound did not result in increased brain uptake. Uptake of an 125I-labeled anti-folate receptor antibody into the brain was very low, and no competition was observed with unlabeled antibody. Imaging of brain thin-sections and whole brain tissue from a mouse injected with folate-fluorescein revealed strong fluorescence in the CP, but virtually no where else in the brain.
CONCLUSIONS: Both fluorescence and radioimaging results demonstrate specific uptake of small molecular weight folate conjugates into CP cells of the murine brain, but no significant transport of the molecules across the CSF. Furthermore, no uptake of larger folate-linked proteins by choroid plexus cells is observed, suggesting folate conjugate size may strongly influence access to CP folate receptors.
METHODS: Balb/c mice were injected with radioactive and fluorescent conjugates of folate to measure and image their uptake by the CP.
RESULTS: Retention of a radioactive folate conjugate, folate-diethylenetriaminepentaacetic acid (DTPA)-111In, into the brain of balb/c mice was observed, although repeated injections or prolonged release via an osmotic pump of the compound did not result in increased brain uptake. Uptake of an 125I-labeled anti-folate receptor antibody into the brain was very low, and no competition was observed with unlabeled antibody. Imaging of brain thin-sections and whole brain tissue from a mouse injected with folate-fluorescein revealed strong fluorescence in the CP, but virtually no where else in the brain.
CONCLUSIONS: Both fluorescence and radioimaging results demonstrate specific uptake of small molecular weight folate conjugates into CP cells of the murine brain, but no significant transport of the molecules across the CSF. Furthermore, no uptake of larger folate-linked proteins by choroid plexus cells is observed, suggesting folate conjugate size may strongly influence access to CP folate receptors.