Table 1.

BBB regulation strategies and related advantages and disadvantages.

BBB Modulation Targets	Strategies	Advantages	Disadvantages
Tight junctions	Osmotic disruption	Transient and reversible	Nonselective, uncontrolled flow, invasive, anesthesia, and side effects
	Radiation-mediated disruption	Disease-specific	Unclear mechanisms and acute, subacute, and chronic dose-dependent toxicity
	Activating bradykinin B2 receptor	Disease-specific, rapid and transient	Limited application to only brain tumor and peripheral side effects
	Direct interference	Transient and reversible	Peripheral side effects
Active efflux	Direct Inhibition	Transient and reversible…	Tolerability concerns of the inhibitor, and side effects to both brain and peripheral tissues
	Targeting regulatory pathways	Disease-specific	Slow and side effects
Transcytosis	Upregulation of LRP1	Drug-specific	Slow and possible LRP1-associated side effects
	Inhibition of Mfsd2a	Transient and reversible	Possible Mfsd2a-associated side effects
	Upregulation of GLUT1	Efficient	Fasting-associated poor compliance