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. 2018 Jul 3;8:239. doi: 10.3389/fonc.2018.00239

Table 3.

Techniques to overcome the blood:brain barrier (BBB).

Technique PK advantage Disadvantage
High-dose systemic chemotherapy Higher Cmax in circulation may result in higher Cmax in central nervous system (CNS) (assuming linear increase in BBB penetration)

  • Toxicity

  • if threshold for BBB penetration is reached, toxicity is increased without increasing chance of benefit

  • If no drug penetrates at low dose, unlikely to achieve drug penetration at higher doses
BBB disruption Temporary increase in BBB penetration into CNS

  • Toxicity

  • Not tumor specific

  • Unknown exposure (adequate concentration over adequate time periods)
Inhibition of drug efflux transporters Block drug efflux from BBB allowing increased CNS penetration

  • Toxicity

  • Results in increased plasma drug levels due to decreased drug clearance (P-glycoprotein inhibitors not specific for BBB)
Intraarterial delivery Higher drug concentrations in region supplied by artery ONLY during first pass through tumor

  • Streaming effect, inhomogeneous delivery (toxicity, insufficient delivery)

  • Unable to reach tumor cells outside of area supplied by artery

  • Once drug enters systemic circulation, no longer any PK advantage
Convection-enhanced delivery Bypasses BBB; direct installation into tumor bed

  • Invasive procedure

  • Difficult to reach all tumor cells

  • Need to ensure adequate exposure of active agent for a long enough period of time but difficult to evaluate PK