Modulation of brain tumor capillaries for enhanced drug delivery selectively to brain tumor.

作者: Keith L. Black , Nagendra S. Ningaraj

DOI: 10.1177/107327480401100304

关键词: Convection-Enhanced DeliveryPermeability (electromagnetism)Nanoparticles for drug delivery to the brainCapillary endothelial cellsCellular mechanismMedicinePathologyDrug deliveryBrain tumorCancer researchVesicle

摘要: Background The blood-brain tumor barrier (BTB) significantly impedes delivery of most hydrophilic molecules to brain tumors. Several promising strategies, however, have been developed overcome this problem. Methods We discuss several drug methods tumor, including intracerebroventricular, convection enhanced delivery, BBB/BTB disruption, and BTB permeability modulation, which was in our laboratory. Results Using immunolocalization, immunoblotting, potentiometric studies, we found that capillary endothelial cells overexpress certain unique protein markers are absent or barely detectable normal cells. biochemically modulated these sustain enhance varying sizes, selectively tumors rat syngeneic xenograft models. also demonstrated the cellular mechanism for vasomodulator-mediated increase is due accelerated formation pinocytotic vesicles transport therapeutic across BTB. Conclusions Other deliver drugs effective but severe drawbacks. Our strategy targets BTB-specific proteins antineoplastic with few no side effects, thus increasing possibility improving treatment.

参考文章(38)
R. J. Boado, W. M. Pardridge, K. L. Black, P. A. Cancilla, Blood-brain barrier and new approaches to brain drug delivery. Western Journal of Medicine. ,vol. 156, pp. 281- ,(1992)
Damir Janigro, Marco Cavaglia, Miranda Kapural, Barbara Ayumar, Peter Rasmussen, Vince Fazio, Nicola Marchi, Kelly Kight, Ben Albensi, Andrew Kanner, Marc R. Mayberg, Peripheral markers of brain damage and blood-brain barrier dysfunction Restorative Neurology and Neuroscience. ,vol. 21, pp. 109- 121 ,(2003)
Lawrence K. Fung, Marian Shin, Betty Tyler, Henry Brem, W. Mark Saltzman, Chemotherapeutic drugs released from polymers : Distribution of 1,3-bis(2-chloroethyl)-1-nitrosourea in the rat brain Pharmaceutical Research. ,vol. 13, pp. 671- 682 ,(1996) , 10.1023/A:1016083113123
A. Gregor, M. Lind, H. Newman, R. Grant, D.M. Hadley, T. Barton, C. Osborn, Phase II studies of RMP-7 and carboplatin in the treatment of recurrent high grade glioma Journal of Neuro-oncology. ,vol. 44, pp. 137- 145 ,(1999) , 10.1023/A:1006379332212
Koichiro Matsukado, Keith L. Black, Shin Nakano, Increased Brain Tumor Microvessel Permeability after Intracarotid Bradykinin Infusion Is Mediated by Nitric Oxide Cancer Research. ,vol. 56, pp. 4027- 4031 ,(1996)
Nagendra S Ningaraj, Keith L Black, Mamatha K Rao, Adenosine 5'-triphosphate-sensitive potassium channel-mediated blood-brain tumor barrier permeability increase in a rat brain tumor model. Cancer Research. ,vol. 63, pp. 8899- 8911 ,(2003)
Kazuhiro Hashizume, Zutang Chen, Ken Samoto, Nagendra Ningaraj, Kamlesh Asotra, Keith L. Black, Yunhui Liu, Correlation between bradykinin-induced blood-tumor barrier permeability and B2 receptor expression in experimental brain tumors. Neurological Research. ,vol. 23, pp. 379- 387 ,(2001) , 10.1179/016164101101198596
Jian Yi Li, Ruben J. Boado, William M. Pardridge, Blood—Brain Barrier Genomics Journal of Cerebral Blood Flow and Metabolism. ,vol. 21, pp. 61- 68 ,(2001) , 10.1097/00004647-200101000-00008
Abesh Kumar Bhattacharjee, Tatsuya Nagashima, Takeshi Kondoh, Norihiko Tamaki, Quantification of early blood-brain barrier disruption by in situ brain perfusion technique. Brain Research Protocols. ,vol. 8, pp. 126- 131 ,(2001) , 10.1016/S1385-299X(01)00094-0
N.S. Ningaraj, M. Rao, K.L. Black, Calcium-dependent potassium channels as a target protein for modulation of the blood-brain tumor barrier. Drug News & Perspectives. ,vol. 16, pp. 291- 298 ,(2003) , 10.1358/DNP.2003.16.5.878815