Table 1. Drug targeting to the central nervous system.

Method & Key References	Rationale	Limitations
In vitro barrier systems 61– 64	Potential for high-throughput screening	In vitro transformation of cell properties. Only limited gene expression of in vivo characteristics
Receptor- or adsorptive- mediated transcytosis 60, 108	Uses known receptors (e.g. Tf, insulin) & cellular mechanisms	Not restricted to brain; only about 15% reaches brain. Limited capacity
Influx transporters
SLC transporters 109	Naturally occurring transporters that also transport wide range of drugs	Many of the transporters are ubiquitously expressed, widespread effects likely. Limited transport capacity. Drugs may also be substrates for ABC efflux transporters
Efflux transporters
Inhibition of efflux transporters 110	ABC transporters are major reason for drugs not reaching brain	Not restricted to brain, widespread side effects likely from both drug entry into other organs and entry of other xenobiotics that may be present
Modulation of integrity of the blood-brain barrier
See Table 2
Bypassing the barriers
Convection-enhanced delivery 111	Localized delivery to site of pathology	Invasive. Potential damaging effect not yet fully evaluated
Injection into CSF 112	Bypasses barriers	Invasive, requires repeated administration or infusion, not targeted to sites of pathology