Penetration of the blood-brain barrier: enhancement of drug delivery and imaging by bacterial glycopeptides.
The blood-brain barrier restricts the passage of many pharmacological agents into the brain parenchyma. Bacterial glycopeptides induce enhanced blood-brain barrier permeability when they are present in the subarachnoid space during meningitis. By presenting such glycopeptides intravenously, blood-brain barrier permeability in rabbits was enhanced in a reversible time- and dose-dependent manner to agents < or = 20 kD in size. Therapeutic application of this bioactivity was evident as enhanced penetration of the antibiotic penicillin and the magnetic resonance imaging contrast agent gadolinium-diethylene-triamine-pentaacetic acid into the brain parenchyma.
Spellerberg
B
B
Laboratory of Molecular Infectious Diseases, Rockefeller University, New York 10021, USA.
Prasad
S
S
Cabellos
C
C
Burroughs
M
M
Cahill
P
P
Tuomanen
E
E
D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000033:anatomy & histology / Q000648:ultrastructure; D003287:Contrast Media; D019786:Gadolinium DTPA; D006020:Glycopeptides / Q000494:pharmacology*; D006193:Haemophilus influenzae / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008969:Molecular Sequence Data; D009942:Organometallic Compounds; D010406:Penicillins / Q000493:pharmacokinetics*; D004369:Pentetic Acid / Q000031:analogs & derivatives; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000737:chemistry
D001426:Bacterial Proteins; D003287:Contrast Media; D006020:Glycopeptides; D009942:Organometallic Compounds; D010406:Penicillins; D004369:Pentetic Acid; D019786:Gadolinium DTPA