Manipulating blood-brain barrier permeability for CNS drug delivery
Pharmaceutical intervention in the CNS is hampered by the shielding function of the blood-brain barrier (BBB). We found that the volatile anesthetics increase BBB permeability in a dose-dependent manner. Mechanistically isoflurane disturbs the organization of membrane lipid nanodomains and triggers caveolar transport across the BBB. In a therapeutic glioblastoma trial in mice, simultaneous exposure to isoflurane and cytotoxic agent improves efficacy of chemotherapy.
Fig. 1: Increased size of membrane lipid nanodomains in primary endothelial cells after isoflurane exposure.
Fig. 2: Increased density of caveolar profiles in brain capillaries after isoflurane exposure.
Fig. 3: Working model. Anesthesia triggers drug delivery to experimental glioma in mice by hijacking caveolar transport (Anesthesia triggers drug delivery to experimental glioma in mice by hijacking caveolar transport | Neuro-Oncology Advances | Oxford Academic (oup.com))