Effect of blood-brain barrier and blood-tumor barrier modification on central nervous system liposomal uptake.
In this study of 25 central nervous system (CNS) tumor-bearing rats, the CNS biodistribution of intravenously administered, indium-labeled liposomes was investigated. In 16 animals, the blood-brain barrier and blood-tumor barrier were modified using intracarotid administration of etoposide. In control animals, analysis by autoradiography and well-counting experiments demonstrated uptake of liposomes in the tumor-bearing hemisphere (% injected dose/g tissue = 0.135) with minimal uptake in the non-tumor-bearing hemisphere (% injected dose/g tissue = 0.007), p < 0.01. Unilateral intracarotid etoposide administration enhanced liposome uptake in both hemispheres-0.215 and 0.023 (tumor-bearing and nontumor-bearing), respectively. The presence of meningeal tumor involvement in nontumor-implanted hemispheres increased liposomal uptake 10-fold. These findings may have clinical applicability in designing therapeutic protocols for the treatment of CNS tumors.
Gennuso
R
R
Division of Neurosurgery, New Jersey's Neuroscience Institute, JFK Medical Center, New York, New York.
Spigelman
M K
MK
Chinol
M
M
Zappulla
R A
RA
Nieves
J
J
Vallabhajosula
S
S
Alberto Paciucci
P
P
Goldsmith
S J
SJ
Holland
J F
JF
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D002199:Capillary Permeability / Q000187:drug effects; D002279:Carcinoma 256, Walker / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D008081:Liposomes / Q000493:pharmacokinetics*; D009368:Neoplasm Transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley
D007205:Indium Radioisotopes; D008081:Liposomes; D005047:Etoposide