Journal
PHARMACEUTICAL RESEARCH
Volume 20, Issue 5, Pages 714-719Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1023/A:1023421232689
Keywords
folic acid; choroid plexus; folate receptor; fluorescein; blood CSF barrier
Funding
- NCI NIH HHS [CA89581] Funding Source: Medline
Ask authors/readers for more resources
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)-In-111, 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 I-125-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available