- The blood-brain barrier restrict the brain delivery of most currently active anticancer agents used in the treatment of brain tumours.
- The magnitude of this restriction is extremely large (50-200 fold) for some of the most commonly used agents cytotoxic agents (paclitaxel, doxorubicin, vinorelbine,) and newer molecularly-target agents.
- In only a very small subset (<5%) of brain metastases is the barrier sufficiently compromised to allow marked drug accumulation.
- This restriction was found in matching human brain metastases.
- This drug delivery compromise can be overcome in brain metastases using several approaches, including drug agents which show poor affinity for barrier active efflux transport, enhanced barrier passive permeability, elevated active efflux, or molecularly targeting mechanism, such as those in using LRP, transferrin, insulin receptor, or other mechanisms.
Stephen Buckley, Head of Department, Absorption and Biological MS, Novo Nordisk