Methamphetamine enhances caveolar transport of therapeutic agents across the rodent blood-brain barrier
Jui-Hsien Chang, Chris Greene, Karen Frudd, Leonardo Araujo dos Santos, Clare E. Futter, Benjamin J. Nichols, Matthew Campbell, Patric Turowski
Abstract
. Notably, METH leaves tight junctions intact and induces transient leakage via caveolar transport, which is suppressed at 4°C and in caveolin-1 (CAV1) knockout mice. METH enhances brain penetration of both small therapeutic molecules, such as doxorubicin (DOX), and large proteins. Lastly, METH improves the therapeutic efficacy of DOX in a mouse model of glioblastoma, as measured by a 25% increase in median survival time and a significant reduction in satellite lesions. Collectively, our data indicate that caveolar transport at the adult BBB is agonist inducible and that METH can enhance drug delivery to the CNS.