|
|
Extensive Distribution of Liposomes in
Rodent Brains and Brain Tumors Following Convection-Enhanced Delivery
Christoph Mamot, John B. Nguyen, Micheal Pourdehnad,
Piotr Hadaczek, Ryuta Saito, John R. Bringas, Daryl C. Drummond, Keelung Hong,
Dmitri B. Kirpotin, Tracy McKnight, Mitchel S. Berger, John W. Park, Krys S.
Bankiewicz
Division
of Hematology-Oncology (C.M.,
J.W.P.), Department of Neurosurgery, Brain Tumor Research Center (J.B.N.,
M.P., P.H., R.S., J.R.B., M.S.B, K.S.B), California Pacific Medical Center Research Institute,
Liposome Research Laboratory (D.C.D., D.B.K.);
Department of Radiology, University of California at San Francisco (UCSF), San
Francisco CA 94115, USA (T.M.); Hermes Biosciences, Inc., South San Francisco,
CA, USA (D.C.D., D.B.K.,
K.H.).
Liposomes labeled with various markers were subjected to local–regional
administration with either direct injection or convection-enhanced delivery
(CED) into rodent brains and brain tumor models.
Direct injection of liposomes containing attached or encapsulated fluorochromes
and/or encapsulated gold particles indicated that tissue localization of
liposomes could be sensitively and specifically detected in the central nervous
system (CNS).
When CED was applied, liposomes achieved extensive and efficient distribution
within normal mouse brains.
Co-infusion of mannitol further increased tissue penetration of liposomes.
Liposomes were also loaded with gadodiamide to monitor their CNS distribution in
rats by magnetic resonance imaging (MRI).
CED-infused liposomes were readily seen on MRI scans as large regions of intense
signal at 2 h, and more diffuse regions at 24
h.
Finally, labeled liposomes were infused via CED into tumor tissue in glioma
xenograft models in rodent hosts.
In intracranial U-87 glioma xenografts, CED-infused liposomes had distributed
throughout tumor tissue, including extension into surrounding normal
tissue.
Greater penetration was observed using 40 versus 90
nm liposomes, as well as with mannitol co-infusion.
To our knowledge, this is the first report of CED infusion of liposomes into the
CNS.
We conclude that CED of liposomes in the CNS is a feasible approach, and offers
a promising strategy for targeting therapeutic agents to brain tumors.
Keywords: brain tumors, CNS, convection-enhanced delivery, glioblastoma, liposomes
Copyright ©
2004 Kluwer Academic Publishers.
All rights reserved
Source:
http://journals.kluweronline.com/article.asp?PIPS=5268432
|
