Potential approaches for drug delivery to the brain: Past, present, and future

Critical Reviews in Therapeutic Drug Carrier Systems

Volumn 27, Issue 3, 2010, Pages 187-236

  Soni, Vandana ^a   Jain, Anekant ^a   Khare, Piush ^a   Gulbake, Arvind ^a   Jain, Sanjay K ^a  

^a DR H S GOUR UNIVERSITY   (India)

Author keywords

blood brain barrier; brain tumor; permeability; prodrugs

Indexed keywords

AMINE OXIDASE (FLAVIN CONTAINING) ISOENZYME B; AMINO ACID DECARBOXYLASE; CHOLINESTERASE; CYTOCHROME P450; DENDRIMER; DNA; GAMMA GLUTAMYLTRANSFERASE; GLUTAMYL AMINOPEPTIDASE; INSULIN; LECTIN; LIPOSOME; MICROSOMAL AMINOPEPTIDASE; NANOPARTICLE; PRODRUG; SOMATOMEDIN B; SOMATOMEDIN C; TRANSFERRIN; DRUG;

ACTIVE TRANSPORT; ALZHEIMER DISEASE; BLOOD BRAIN BARRIER; BLOOD CEREBROSPINAL FLUID BARRIER; BRAIN TARGETED CHEMICAL DELIVERY SYSTEM; BRAIN TUMOR; CELL FREE SYSTEM; CELL LINE; CHOROID PLEXUS; COCULTURE; DIFFUSION; DRUG DELIVERY SYSTEM; DRUG DESIGN; DRUG TRANSPORT; ENDOCYTOSIS; ENDOTHELIUM CELL; GENE TARGETING; HUMAN; IMPLANT; LIGAND BINDING; NONHUMAN; PARTITION COEFFICIENT; REVIEW; STEM CELL; TRANSCYTOSIS; ANIMAL; BIOLOGICAL MODEL; BRAIN; BRAIN NEOPLASMS; CEREBROSPINAL FLUID; CULTURE TECHNIQUE; DRUG EFFECTS; ENZYMOLOGY; METABOLISM; PHARMACEUTICS; PHYSIOLOGY; PROCEDURES; STEM CELL TRANSPLANTATION; TRANSPORT AT THE CELLULAR LEVEL; TRENDS; VASCULARIZATION;

ANIMALS; BIOLOGICAL TRANSPORT; BLOOD-BRAIN BARRIER; BRAIN; BRAIN NEOPLASMS; CELL CULTURE TECHNIQUES; CEREBROSPINAL FLUID; DRUG DELIVERY SYSTEMS; HUMANS; MODELS, BIOLOGICAL; PHARMACEUTICAL PREPARATIONS; STEM CELL TRANSPLANTATION; TECHNOLOGY, PHARMACEUTICAL;

EID: 77954334041     PISSN: 07434863     EISSN: None     Source Type: Journal    
DOI: 10.1615/CritRevTherDrugCarrierSyst.v27.i3.10     Document Type: Review

References (207)

1. Ehrlich P. Uber die Beziehungen von chemische constitution, vertheilung, uns pharmakologischer wirkung. In: Collected Studies on Immunity. New York (NY): John Wiley & Sons; 1906. p. 567-595
2. Vitalfaerbung am Zentralnervensystem. Berlin: G. Reimer; Abh. preuss. Akad. Wis. 1913-14;1:1-60.
3. Stern L, Gautier R. Les repports enter le liquide cephalo-rachidien et les elements nerveux de I'axe cerebrospinal. Arch Intern Physiol. 1922;17:391-448.
4. Friedemann U. Blood-brain barrier. Physiol Rev. 1942;22:125-145
5. Broman T. On basic aspects of the blood-brain barrier. Acta Psychiatr Neurol Scand. 1955;30:115-124
6. Reese TS, Karnovsky MJ. Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol. 1967;34:207-217
7. Brightman MW, Klatzo I, Olsson Y, Reese TS. The blood-brain barrier to proteins under normal and pathological conditions. J Neurol Sci. 1970;10:215-239
8. Begley DJ. The blood-brain barrier: principles for targeting peptides and drugs to the central nervous system. J Pharm Pharmacol. 1996;48:136-146
9. Schlossauer B, Steuer H. Comparative anatomy, physiology and in vitro models of the blood-brain and blood-retina barrier. Curr Med Chem. 2002;2:175-186
10. Nehls V, Denzer K, Drenckhahn D. Pericyte involvement in capillary sprouting during angiogenesis in situ. Cell Tissue Res. 1992;270:469-474
11. Larson KB, Markham J, Raichle ME. Tracer-kinetic models for measuring cerebral blood flow using externally detected radiotracers. J Cereb Blood Flow Metab. 1987;7:443-463
12. Frank RA, Markou A, Wiggins LL. A systematic evaluation of the properties of train duration response functions. Behav Neurosci. 1987;101:546-559
13. Antonelli-Orlidge A, Saunders KB, Smith SR, D'Amore PA. An activated form of transforming growth factor beta is produced by cocultures of endothelial-cells and pericytes. Proc Natl Acad Sci U S A. 1989;86:4544-4548
14. Hellstrom M, Gerhardt H, Kalen M, Li X, Eriksson U, Wolburg H, Betsholts C. Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J Cell Biol. 2001;153:543-554
15. Coomber BL, Stewart PA. Morphometric analysis of CNS microvascular endothelium. Microvasc Res. 1985;30:99-115.
16. Minakawa T, Bready J, Berliner J, Fisher M, Cancilla PA. In vitro interaction of astrocytes and pericytes with capillary-like structures of brain microvessel endothelium. Lab Invest. 1991;65:32-40.
17. Brightman TS, Reese MJ. Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol. 1967;34:207-217
18. Beck J, Schettini A, Salton R. Application of the coplanar principle to dynamic epidural pressure measurements. J Neurosurg. 1984;61:733-736
19. Arthur FE, Shivers RR, Bowman PD. Astrocyte-mediated induction of tight junctions in brain capillary endothelium: an efficient in vitro model. Brain Res. 1987;433:155-159
20. Cancilla PA, DeBault LE. Neutral amino acid transport properties of cerebral endothelial cells in vitro. J Neuropathol Exp Neurol. 1983;42:191-199
21. Hynes RO. Specificity of cell adhesion in development: the cadherin superfam- ily. Curr Opin Genet Dev. 1992;2:621-624.
22. Wolburg H, Rohlmann A. Structure-function relationships in gap junctions. Int Rev Cytol. 1995;157:315-373
23. Tontsch U, Bauer HC. Glial cells and neurons induce blood-brain barrier related enzymes in cultured cerebral endothelial cells. Brain Res. 1991;539:247-253
24. Brightman M. Ultrastructure of brain endothelium. In: Bradbury MWB, editor. Physiology and pharmacology of the blood-brain barrier (Handbook of experimental pharmacology). Berlin, Germany: Springer-Verlag; 1992. p. 1-22.
25. Crone C, Christensen O. Electric resistance of a capillary endothelium. J Gen Physiol. 1981;77:349-371
26. Butt A, Jones HC, Abbott NJ. Electric resistance across the blood-brain barrier in anesthetized rat: a developmental study. J Physiol. 1990;429:47-62.
27. Furuse M, Sasaki H, Tsukita S. Manner of interaction of heterogeneous claudin species within and between tight junction strands. J Cell Biol. 1999;147:891-903.
28. Hirase T, Hirase T, Staddon JM, Saitou M, Ando-Akatsuka Y, Itoh M, Furuse M, Fujimoto K, Tsukita S, Rubin LL. Occludin as a possible determinant of tight junction permeability in endothelial cells. J Cell Sci. 1997;110:1603-1613 (Pubitemid 27338748)
29. Martin-Padura I, Lostaglio S, Schneemann M, Williams L, Romano M, Fruscella P, Panzeri C, Stoppacciaro A, Ruco L, Villa A, Simmons D, Dejana E. Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration. J Cell Biol. 1998;142:117-127
30. Haskins J, Gu L, Wittchen ES, Hibbard J, Stevenson BR. ZO-3 a novel member of the MAGUK protein family found at the tight junction interacts with ZO-1 and occludin. J Cell Biol. 1998;141:199-208.
31. Lapierre LA. The molecular structure of the tight junction. Adv Drug Del Rev. 2000;41:255-264
32. Cordenonsi M, D'Atri F, Hammar E, Parry DA, Kendrick-Jones J, Shore D, Citi S. Cingulin contains globular and coiled-coil domains and interacts with ZO-1, ZO-2, ZO-3 and myosin. J Cell Biol. 1999;147:1569-1582
33. Itoh M, Furuse M, Morita K, Kubota K, Saitou M, Tsukita S. Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins. J Cell Biol. 1999;147:1351-1363
34. Hirokawa N, Tilney LG. Interactions between actin filaments and between actin filaments and membranes in quick-frozen and deeply etched hair cells of the chick ear. J Cell Biol. 1982;95:249-261
35. Takeichi M, Matsunami H, Inoue T, Kimura Y, Suzuki S, Tanaka T. Roles of cad- herins in patterning of the developing brain. Dev Neurosci. 1997;19:86-87
36. Yagi T, Takeichi M. Cadherin superfamily genes: functions, genomic organization, and neurologic diversity. Genes Dev. 2000;14:1169-1180 (Pubitemid 30327498)
37. Bentzel CJ, Hainau B, Edelman A, Anagnostopoulos T, Benedetti EL. Effect of plant cytokinins on microfilaments and tight junction permeability. Nature. 1976;264:666-668 (Pubitemid 8020874)
38. Stevenson BR, Begg DA. Concentration-dependent effects of cytochalasin D on tight junctions and actin filaments in MDCK epithelial cells. J Cell Sci. 1994;107:367-375
39. Tsukamoto T, Nigam SK. Tight junction proteins form large complexes and associate with the cytoskeleton in an ATP depletion model for reversible junction assembly. J Biol Chem. 1997;272:16133-16139
40. Davson H, Segal MB. Physiology of the CSF and blood-brain barriers. Boca Raton (FL): CRC Press; 1995.
41. Nabeshima S, Reese TS, Landis DM, Brightman MW. Junctions in the menin- ges and marginal glia. J Comp Neurol. 1975;164:127-169
42. Brightman MW. The intracerebral movement of proteins injected into blood and cerebrospinal fluid of mice. Prog Brain Res. 1968;29:19-40.
43. Cole DJ, Schell RM, Przybelski RJ, Drummond JC, Bradley K. Focal cerebral ischemia in rats: effect of hemodilution with alpha-alpha cross-linked hemoglobin on CBF. J Cereb Blood Flow Metab. 1992;12:971-976
44. Takasato Y, Rapoport SI, Smith QR. An in situ brain perfusion technique to study cerebrovascular transport in the rat. Am J Phys. 1984;247:H484-93.
45. Pardridge WM, Triguero D, Yang J, Cancilla PA. Comparison of in vitro and in vivo models of drug transcytosisi through the blood- brain barrier. J Pharm Exp Ther. 1990;253:884-891
46. Gibaldi M, Perrier D. Pharmacokinetics model. New York (NY): Dekker Inc; 1982.
47. Pardridge WM, Boado RJ, Kang YS. Vector-mediated delivery of a polyamide ("peptide") nucleic acid analogue through the blood-brain barrier in vivo. Proc Natl Acad Sci U S A. 1995;92:5592-5596
48. Sadeque AJ, Wandel C, He H, Shah S, Wood AJ. Increased drug delivery to the brain by P-glycoprotein inhibition. Clin Pharmacol Ther. 2000;68:231-237
49. Savolainen J, Edwards JE, Morgan ME, McNamara PJ, Anderson BD. Effects of a P-glycoprotein inhibitor on brain and plasma concentrations of anti-human immunodeficiency virus drugs administered in combination in rats. Drug Metab Dispos. 2002;30:479-482
50. Fellner S, Bauer B, Miller DS, Schaffrik M, Fankhanel M, Spruss T, Bernhardt G, Graeff C, Farber L, Gschaidmeier H, Buschauer A, Fricker G. Transport of paclitaxel (Taxol) across the blood-brain barrier in vitro and in vivo. J Clin Invest. 2002;110:1309-1318
51. Cornford EM, Diep CP, Pardridge WM. Blood-brain barrier transport of valproic acid. J Neurochem. 1985;44:1541-1550
52. Boyle FM, Eller SL, Grossman SA. Penetration of intra-arterially administered vincristine in experimental brain tumor. Neuro Oncol. 2004;6:300-305
53. Murata M, Tamai I, Kato H, Nagata O, Tsuji A. Efflux transport of a new quinolone antibacterial agent, HSR-903 across the blood-brain barrier. J Pharmacol Exp Ther. 1999;290:51-57
54. Tamai I, Tsuji A. Drug delivery through the blood-brain barrier. Adv Drug Del Rev. 1996;19:401-424
55. Pardridge WM, Triguero D, Buciak J, Yang J. Evaluation of cationized rat albumin as a potential blood-brain barrier drug transport vector. J Pharmacol Exp Ther. 1990;255:893-899
56. Zlokovic BV. Cerebrovascular permeability to peptides: manipulations of transport systems at the blood-brain barrier. Pharm Res. 1995;12:1395-406
57. Pardridge WM. CNS drug design based on principles of blood-brain barrier transport. J Neurochem. 1998;70:1781-1792
58. Einstein A. Investigations on the Theory of the Brownian Movement [English translation]. New York (NY): Dover; 1956.
59. Vorbrodt AW. Demonstration of anionic sites on the luminal and ablumi- nal fronts of endothelial cells with poly-L-lysine-gold complex. J Histochem Cytochem. 1987;35:1261-1266
60. Vorbrodt AW. Ultracytochemical characterization of anionic sites in the wall of brain capillaries. J Neurocytol. 1989;18:359-368
61. Griffin DE, Giffels J. Study of protein characteristics that influence entry into the cerebrospinal fluid of normal mice and mice with encephalitis. J Clin Invest. 1982;70:289-295
62. Belting M. Heparan sulfate proteoglycan as a plasma membrane carrier. Trends Biochem Sci. 2003;28:145-151
63. Franchise H, Nicolae G, Jean-Michel S. CNS delivery via adsorptive transcy- tosis. AAPS J. 2008;10:455-472
64. Pardridge WM. Advances in cell biology of blood-brain barrier transport. Semin Cell Biol. 1991;2:419-426
65. Pardridge WM. Brain capillary endothelium transport of insulin. In: Simio- nescu N, Simionescu M, editors. Endothelial cell dysfunctions. New York (NY): Plenum Press; 1992. p. 347-362
66. Pardridge WM. Vector-mediated peptide drug delivery to the brain. Adv Drug Del Rev. 1995;15:109-146
67. Prieto P, Blaauboer BJ, de Boer AG, Boveri M, Cecchelli R, Clemedson C, Coecke S, Forsby A, Galla HJ, Garberg P, Greenwood J, Price A, Tahti H. Blood-brain barrier in vitro models and their application in toxicology. The report and recommendations of ECVAM Workshop 49. Altern Lab Anim. 2004;32:37-50.
68. Oldendorf WH. Measurement of brain uptake of radiolabeled substances using a tritiated water internal standard. Brain Res. 1970;24:1629-1639
69. Kakee A, Terasaki T, Sugiyama Y. Brain efflux index as a novel method of solute analyzing efflux transport at the blood-brain barrier. J Pharmacol Exp Ther. 1996;277:1550-1559 (Pubitemid 27167171)
70. Begley DJ, Squires LK, Zlokovic BV, Mitrovic DM, Hughes CCW, Revest PA, Greenwood J. Permeability of the blood-brain barrier to the immunosuppres- sive cyclic peptide cyclosporine A. J Neurochem. 1998;55:1222-1230
71. De lange ECM, De Boer AG, Breimer DD. Monitoring in-vivo BBB drug transport: CSF sampling, the unit impulse response method and with special reference intracerebral microdialysis. STP Pharm Sci. 1997;7:17-28.
72. Takasato Y, Rapoport SI, Smith QR. An in situ brain perfusion technique to study cerebrovascular port in the rat. Am J Physiol. 1984;247:H484-93.
73. Terasaki T, Deguchi Y, Kasama Y, Pardridge WM, Tsuji A. Determination of in vivo steady-state unbound drug concentration in the brain interstitial fluid by microdialysis. Int J Pharm. 1992;81:143-152
74. Menacherry S, Hubert W, Justice JB. In vivo calibration of microdialysis probes for exogenous compounds. Anal Chem. 1992:64:577-583
75. Rubin LL, Staddon JM. The cell biology of the blood-brain barrier. Ann Rev Neurosci.1999;22:11-23.
76. Garberg P. In vitro models of the blood-brain barrier. Altern Lab Anim. 1998;26:821-847
77. Meresse S, Dehouck MP, Delorme P, Bensaid M, Tauber JP, Delbart C, Fruchart JC, Cecchelli R. Bovine brain endothelial cells express tight junctions and mono- amine oxidase activity in long-term culture. J Neurochem. 1989;53:1363-1371
78. Dehouck MP, Meresse S, Delorme P, Fruchart JC, Cecchelli R. An easier, reproducible, and mass production method to study the blood-brain barrier in vitro. J Neurochem. 1990;54:1798-1801
79. Dehouck MP, Dehouck B, Schluep C, Fruchart JC, Lemaire M, Cecchelli R. Drug transport to the brain: comparison between in vitro and in vivo models of the blood-brain barrier. Eur J Pharm Sci. 1995;3:357-365
80. Dehouck MP, Vigne P, Torpier G, Breittmayer JP, Cecchelli R, Frelin C. Endothelin-I as a mediator of endothelial cell-pericyte interactions in bovine brain capillaries. J Cereb Blood Flow Metab. 1997;17:464-469
81. Descamps L, Dehouck MP, Torpier G, Cecchelli R. Receptor-mediated tran- scytosis of transferrin through blood-brain barrier endothelial cells. Am J Physiol. 1996;270:1149-1158
82. Fillebeen C, Descamps L, Dehouck MP, Fenart L, Benaissa M, Spick G, Cec- chelli R, Pierce A. Receptor mediated transcytosis of lactoferrin through the blood-brain barrier. J Bio Chem. 1999;274:7011-7017
83. Cecchelli R, Dehouck B, Descamps L, Fenart L, Buee-Scherrer V, Duhem C, Lun- dquist S, Rentfel M, Torpier G, Dehouck MP. In vitro model for evaluating drug transport across the blood-brain barrier. Adv Drug Del Rev. 1999;36:165-178
84. Lundquist S, Renftel M, Brillault J, Fenart L, Cecchelli R, Dehouck MP. Prediction of drug transport through the blood-brain barrier in vivo: a comparison between two in vitro cell models. Pharma Res. 2002;7:976-981
85. Hoheisel D, Nitz T, Franke H, Wegener J, Hakvoort A, Tilling T, Galla HJ. Hydrocortisone reinforces the blood-brain barrier properties in a serum-free cell culture system. Biochem Biophys Res Comm. 1998;244:231-316.
86. Lohmann C, Hilwel S, Galla HJ. Predicting blood-brain barrier permeability of drugs: evaluation of different in vitro assays. J Drug Target. 2002;10:263-276
87. Eisenblatter T, Huwel S, Galla HJ. Characterisation of the brain multidrug resistance protein (BMDP/ABCG2/BCRP) expressed at the blood-brain barrier. Brain Res. 2003;971:221-231
88. Nitz T, Eisenblatter T, Psathaki K, Galla HJ. Serum-derived factors weaken the barrier properties of cultured porcine brain capillary endothelial cells in vitro. Brain Res. 2003;981:30-40.
89. Roux F, Durieu-Trautmann O, Chaverot N, Claire M, Mailly P, Bourre JM, Strosberg AD, Couraud PO. Regulation of gamma-glutamyl transpeptidase and alkaline phosphatase activities in immortalized rat brain microvessel endothelial cells. J Cell Physiol. 1994;159:101-113
90. Blasig IE, Giese H, Schroeter ML, Sporbert A, Utepbergenov DI, Buchwalow IB, Neubert K, Schonfelder G, Freyer D, Schinike I, Siems WE, Paul M, Haseloff RF, Blasig R. NO and oxyradical metabolism in new cell lines of rat brain capillary endothelial cells forming the blood-brain barrier. Microvasc Res. 2001;62:114-127
91. Lechardeur D, Schwartz B, Paulin D, Scherman D. Induction of blood-brain barrier differentiation in a rat brain-derived endothelial cell line. Exp Cell Res. 1995;220:161-170
92. Kido Y, Tamai I, Okamoto M, Suzuki F, Tsuji A. Functional clarification of MCT1-mediated transport of monocarboxylic acids at the blood-brain barrier using in vitro cultured cells and in vivo BUI studies. Pharm Res. 2000;17: 55-62.
93. Muraganandam A, Herx LM, Monette R, Durkin JP, Stanimirovic DB. Development of immortalized cerebromicrovascular endothelial cell line as an in vitro model of the human blood-brain barrier. FASEB J. 1997;11:1187-1197
94. Xiao L, Yang C, Dorovini-Zis K, Tandon NN, Ades E, Lal AA, Udhayakumar V. Plasmodium falciparum: involvement of additional receptors in the cytoadher- ence of infected erythrocytes to microvascular endothelial cells. Exp Parasitol. 1996;84:42-55.
95. Prudhomme JG, Sherman IW, Land KM, Moses AV, Stenglein S, Nelson JA. Studies of Plasmodium falciparum cytoadherence using immortalized human brain capillary endothelial cells. Int J Parasitol. 1996;26:647-655
96. Uyttendaele H, Closson V, Wu G, Roux F, Weinmaster G, Kitajewski J, Notch4 and Jagged-1 induce microvessel differentiation of rat brain endothelial cells. Microvasc Res. 2000;60:91-103. (Pubitemid 30667050)
97. Drexler HG, Quentmeier H, Dirks WG, MacLeod RA. Bladder carcinoma cell line ECV304 is not a model system for endothelial cells. In Vitro Cell Dev Biol Anim. 2002;38:185-186
98. Dirks WG, MacLeod RA, Drexler HG. ECV304 (endothelial) is really T24 (bladder carcinoma): cell line cross-contamination at source. In Vitro Cell Dev Biol Anim. 1999;35:558-559
99. Kallmann BA, Wagner S, Hummel V, Buttmann M, Bayas A, Tonn JC, Rieck- mann P. Characteristic gene expression profile of primary human cerebral endothelial cells. FASEB J. 2002;16:589-591
100. Batrakova EV, Miller DW, Li S, Alakhov VY, Kabanov AN, Elmquist WF. Pluronic P85 enhances the delivery of digoxin to the brain: in vitro and in vivo studies. J Pharmacol Exp Ther. 2001;296:551-557
101. Lundquist S, Renftel M, Brillault J, Fenart L, Cecchelli R, Dehouck MP. Prediction of drug transport through the blood-brain barrier in vivo: a comparison between two in vitro cell models. Pharma Res. 2002;19:976-981
102. Veronesi B. Characterization of the MDCK cell line for screening neurotoxi- cants. Neurotoxicology. 1996;17:433-443
103. Smith BJ, Doran AC, McLean S, Tingley FD, O'Neill BT, Kajiji SM. P-glycopro- tein efflux at the blood-brain barrier mediates differences in brain disposition and pharmacodynamics between two structurally related neurokinin-1 receptor antagonists. J Pharmacol Exp Ther. 2001;298:1252-1259
104. Gaillard PJ, Voorwinden LH, Nielsen JL, Ivanov A, Atsumi R, Engman H, Ringbom C, De-Boer AG, Breimer DD. Establishment and functional characterization of an in vitro model of the blood-brain barrier comprising a co- culture of brain capillary endothelial cells and astrocytes. Eur J Pharm Sci. 2001;12:215-222
105. Kramer SD, Schutz YB, Wunderli-Allenspach H, Abbott NJ, Begley DJ. Lipids in blood-brain barrier models in vitro. II. Influence of glial cells on lipid classes and lipid fatty acids. In Vitro Cell Dev Biol Anim 2002;38:566-571
106. Tahti H, Nevala H, Toimela T. Refining in vitro neurotoxicity testing-the development of blood-brain barrier models. Altern Lab Anim. 2003;31:273-276
107. Telling TH, Engelbertz CH, Decker ST, Karte D, Huwel S, Galla HJ. Expression and adhesive properties of basement membrane proteins in cerebral capillary endothelial cell culture. Cell Tissue Res. 2002;310:19-29.
108. Lohmann C, Krischke M, Wegener J, Galla HJ. Tyrosine phosphatase inhibition induces loss of blood brain barrier integrity by matrix metalloproteinase dependent and independent pathway. Brain Res. 2004;995:184-186
109. Toimela T, Maenpaa H, Mannerstrom M, Tahti H. Development of an in vitro blood-brain barrier model-cytotoxicity of mercury and aluminum. Toxicol App Pharmacol. 2004;195:73-82.
110. Neuwelt EA, Barnett PA, Ramsey F, Hellstrom KE, Hellstrom I, McCormick CL. Effect of blood brain barrier disruption on intact and fragmented monoclonal antibody localization in intracerebral lung carcinoma xenograft. J Nucl Med. 1994;35:1831-1841
111. Salahuddin TS, Kalimo H, Johansson BB, Olsson Y. Structural changes in the rat brain after carotid infusions of hyperosmolar solutions. An electron microscopic study. Acta Neuropathol. 1988;77:5-11.
112. Richmon JD, Fukuda K, Sharp FR, Noble LJ. Induction of HSP-70 after hyperosmotic opening of the blood-brain barrier in the rat. Neurosci Lett. 1995;202:1-9.
113. Tamargo RG, Myseros JS Epstein JI, Yang MB, Chasin M, Brem H. Interstitial chemotherapy of the 9L gliosarcoma: controlled release polymers for drug delivery in the brain. Cancer Res. 1993;53:329-333 (Pubitemid 23031845)
114. Black KL, Baba T, Pardridge WM. Enzymatic barrier protects brain capillaries from leukotriene C4. J Neurosurg. 1994;81:745-751
115. Inamura T, Black KL. Bradykinin selectivity opens blood-tumor barrier in experimental brain tumors. J Cereb Blood Flow Metab. 1994;14:862-870
116. Nakano S, Matsukado K, Black KL. Enhanced cytokine delivery and intercellular adhesion molecule I (I CAM-I) expression in glioma by intracarotid infusion of bradykinin analog RMP-7. Neurol Res. 1997;19:501-508
117. Sipos EP, Tylor B, Piantadosi S, Burger PC, Brem H. Optimizing interstitial delivery of BCNU from controlled release polymers for the treatment of brain tumours. Cancer Chemother Pharmacol. 1997;39:383-389
118. Begley DJ. The blood-brain barrier. Principles for targeting peptides and drug to the central nervous system J Pharm Pharmacol. 1996;48:136-146
119. Tsuji A, Tamai H. Carrier-mediated or specialized transport of drugs across the blood-brain barrier. Adv Drug Del Rev. 1999;36:277-290 (Pubitemid 29121976)
120. Abbriscato TJ, Thomas SA, Hurdy VJ, Davis TP. Brain and spinal cord distribution of biphalin: correlation with opioid receptor density and mechanism of CNS entry. J Neurochem. 1997;69:1236-1245
121. Pardridge WM. Transport of small molecules through the blood brain barrier: biology and methodology. Adv Drug Del Rev. 1995;15:5-36.
122. Nutl J, Woodward WR, Carter JP, Anderson JL. The ′on off phenomenon in Parkinson′s disease. Relation to levodopa absorption and transport. N Engl J Med. 1984;310:483-488
123. Shin SU, Wu D, Ramanathan R, Pardridge WM, Morrison SL. Functional and pharmacokinetic properties of antibody/avidin fusion proteins. J Immunol. 1997;158:4797-4804
124. Penichet ML, Kang, YS, Pardridge WM, Morrison SL, Shin SU. An antibody- avidin fusion protein specific for transferrin receptor serves as a delivery vehicle for effective brain targeting: Initial applications in antisense AIDS drug delivery to the brain. J Immunol. 1999;163:4421-4426
125. Vinogradov S, Betrakova E, Li S, Kabanov A. Polyion complex micelles with protein-modified corona for receptor-mediated delivery of oligonucleotides into cells. Bioconjug Chem. 1999;10:851-860
126. Kang YS, Pardridge WM. Brain delivery of biotin bound to a conjugate of neutral avidin and cationized human albumin. Pharm Res. 1994;11:1257-1264
127. Bickel U, Kang YS. Use of chimeric peptides in drug to brain. In: Paulson U, Kundson GM, Moos T, editors. Brain barrier systems. Alfred Benzon Symposium 45. Copenhagen, Denmark: Munksgaard, 1999.
128. Chester KA, Howkins RE. Clinical issues in antibody design. Trends Biotechnol. 1995;13:294-300.
129. Melton R, Sherwood R. Antibody-enzyme conjugates for cancer therapy. J Nat Cancer Inst. 1996;88:153-165
130. Fishman JB, Rubin JB, Handrahen JV, Connor JR, Fine RE. Receptor-mediated transcytosis of transferrin across the blood-brain barrier. J Neurosci Res. 1987;48:299-304.
131. Fenart L, Dehouck MP, Dehouck B, Torpier G, Cocchelli R. In: Pardridge WM, editor. Introduction to the blood-brain barrier. Cambridge, United Kingdom: Cambridge University Press; 1998. p. 221.
132. Banks WA, Kastin AJ, Huang W, Jaspan JB, Maness L. Leptin enters the brain by a saturable system independent of insulin. Peptides. 1996;17:305-311
133. Golden PL, Macccagnan TJ, Pardridge WM. Human blood-brain barrier leptin receptor. Binding and endocytosis in isolated human brain microvessels. J Clin Invest. 1997;99:14-18
134. Frank HRL, Pardridge WM. A direct in vitro demonstration of insulin binding to isolate brain microvessels. Diabetes. 1981;30:757-761
135. Skarlatos S, Yoshikawa T, Pardridge WM, Transport of [125I] transferrin through the rat blood-brain barrier. Brain Res. 1995;683:164-169
136. Vyas SP, Sihorkar V. Endogenous ligands and carrier in non-immunogenic site-specific drug delivery. Adv Drug Deliv Rev. 2000;43:101-164
137. Kratz F, Beyer U, Roth T. Transferrin conjugates of doxorubicin: synthesis, characterization, cellular uptake, and in vitro efficacy. Cancer Chemother Pharmacol. 1998;41:155-160
138. Sun H, Li H, Sadler PJ. Transferrin as a metal ion mediator. Chem Rev. 1999;99:2817-2842
139. Bouirig II, Eloy D, Jordon P. Formation of reactive deoxygenage singulet photosen- sible par hypericine dans des liposomes de dipalmitoulphosphatidylcholine. Misc en evidence d′unc photooxydation rotardee. J Chim Phys. 1992;89:1391-1411
140. Bickel U. The blood-brain barrier and drug delivery to the CNS. New York (NY): Marcel Dekker Ins; 2001. p. 171.
141. Pardridge WM. Non-invasive drug delivery to the human brain using endogenous blood-brain barrier transport systems. Pharm Sci Today. 1999;2:49-59.
142. Pardridge WM, Kang YS, Buciak JL. Transport of human recombinant brain- derived neurotrophic factor (BDNF) through the rat blood-brain barrier in vivo using vector-mediated peptide drug delivery. Pharm Res. 1994;11:738-746
143. Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol. 1965;13:238-252
144. Greoriadis G. Drug entrapment in liposomes. FEBS Lett. 1973;36:292-96.
145. Greoriadis G, Leathwood PD, Ryhem BE. Enzyme entrapment in liposomes. FEBS Lett. 1971;14:95.
146. Greoriadis G, Allison AC. Entrapment of proteins in liposomes prevents allergic reactions in pre-immunised mice. FEBS Lett. 1974;45:71-74
147. Kimelberg KG. Differential distribution of liposome-entrapped [3H] metho- trexate and labelled lipids after intravenous injection in a primate. Biochem Biophys Acta. 1976;448:531-550
148. Papahajopoulos D, Vali WJ. Incorporation of macromolecules within large unilamellar vesicles (LUV). Ann N Y Acad Sci. 1978;308:259-267
149. Greoriadis G. The carrier potential of liposomes in biology and medicine. N Engl J Med. 1976;295:704-710
150. Gabizon AA. Liposomal anthracyclines. Hematol Clin North Am. 1994;8:431-50.
151. Sigal T, Aviva MD. Doxorubicin encapsulated in sterically stabilized liposomes for the treatment of a brain tumor model: biodistribution and therapeutic efficacy. J Neurosurg. 1995;83:1029-1037
152. Huwyler J, Wu D, Padridge WM. Brain drug delivery of small molecules using immunoliposomes. Proc Natl Acad Sci U S A. 1996;93:14164-14169
153. Qualis MM, Thompson DH. Chloroaluminum phthalocyanine tetrasulfi- mate delivered via acid labile diplasmenylcholine-folate liposomes: intra- cellular localization and synergistic phototoxicity. Int J Cancer. 2001;93: 384-392
154. Reddy JA, Dean D, Kennedy MD. Optimization of folate-conjugated liposomal vectors for folate receptor-mediated gene therapy. J Pharma Sci. 1999;88:1112-1118
155. Gijsens A, Missiaen L, Merlevede W. Epidermal growth factor-mediated targeting of chlorine C6 selectively potentiates its photodynamic activity. Cancer Res. 2000;60:2197-2202
156. Renno RZ, Miller JW. Photosensitizer delivery for photodynamic therapy of choroidal neovascularization. Adv Drug Del Rev. 2001;52:63-71.
157. Gijsens A, Derycke A, Missiaen L. Targeting of the photocytotoxic compound AIPcS4 to HeLa cells by transferrin conjugated PEG liposomes. Int J Cancer. 2002;101:78-85.
158. Opanasopit P, Sakai M, Nishikawa M. Inhibition of liver metastasis by targeting of immunomodulators using mannosulated liposome carrier. J Control Rel. 2002;80:283-294
159. Kreuter J. Nanoparticles. In: Swarbic J, Boylan JC, editors. Encyclopaedia of Pharmaceutical Technology. Vol.10. New York (NY): Marcel Dekker; 1994. p. 165.
160. Soni V, Kohli DV, Jain SK. Transferrin-coupled liposomes as drug delivery carrier for brain targeting of 5-fluorouracil. J Drug Target. 2005;13:245-250 (Pubitemid 41086289)
161. Soni V, Kohli DV, Jain SK. Transferrin conjugated liposomal system for improved delivery of 5-fluorouracil to brain. J Drug Target. 2008;16:73-78
162. Alyautdin RN, Petrov VE, Langer K, Berthold A, Kharkevich DA, Kreuter J. Delivery of loperamide across the blood-brain barrier with polysorbate 80-coated poly butylcyanoacrylate nanoparticles. Pharm Res. 1997;14:325-328
163. Swarbrick J, Boyland JC, editors. Encyclopaedia of pharmaceutical technology. Vol.10. New York (NY): Marcel Dekker; 1994. p. 165.
164. Neuwelt EA, Barnett PA, Pegal M, Glassberg M, Frenkel EP. Pharmacology and toxicity of intracarotid adriamycin administration following osmotic blood- brain barrier modification. Cancer Res. 1981;41:4466-4470
165. Neuwelt EA, Glassberg M, Frenkel EP. Inability of dimethyl sulfoxide and 5-fluorouracil to open the blood brain barrier. Ann Neurol. 1983;14:316-24. Saba TM. Physiology and physiopathology of the reticuloendothelial system. Arch Intern Med. 1970;126:1031-1052
166. Couvereur P, Grislain L, Lenaerts V, Brasseur F, Guiot P, Biernacki A. Blood- brain barrier disruption in the treatment of brain tumors: animal studies. In: Guiot P, Couvreur P, editors. Polymeric nanoparticles and microspheres. Boca Raton (FL): CRC Press; 1986. p. 27.
167. Dehouck B, Fenart CD, Ehouck MP, Pierce A, Torpier G, Cecchelli R. A new unction for the LDL receptor: transcytosis of LDL across the blood-brain bar- "ier. J Cell Biol. 1997;138:877-89.
168. CCordon-cardo C, O'Brien JP, Casals D, Biedler JL, Melamed MR, Bertino JR. Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proc Natl Acad Sci U S A. 1989;86:695-698
169. Zordon-Nudo T, Ling V, Liv Z, Georges E. Effects of nonionic detergents on P-glycoprotein drug binding and reversal of multidrug resistance. Cancer Res. L993;53:5994-6000.
170. Nerurkar MM, Burto PS, Borchardt RT. The use of surfactants to enhance he permeability of peptides through Caco-2 cells by inhibition of an apically polarized efflux system. Pharm Res. 1996;13:528-534
171. Lockman P, Oyewumi M, Koziara J, Roder K, Mumper R, Allen D. Brain uptake 3f thiamine-coated nanoparticles. J Control Rel. 2003;93:271-282
172. Wang JX, Sun X, Zhang ZR. Enhanced braintargeting by synthesis of 3′,5′-diocyanoyl-5-fluoro-2′-deoxyuridine and incorporation into solid lipid nanoparticles. Eur J Pharm Biopharm. 2002;54:285-290
173. Lu W, Tan YZ, Hu KL, Jiang XG. Cationic albumin conjugated PEGylated nanoparticle with its transcytosis ability and little toxicity against blood-brain barrier. Int J Pharm. 2005;295:247-260
174. Jain RK. Delivery of molecular and cellular medicine to solid tumors. J Control Rel.1998;53:49-67.
175. Lindgren M Hallbrink M, Prochiantz A, Langel U. Cell-penetrating peptides. Trends Pharmacol Sci. 2000;21:99-103.
176. Bordor N, Brewster ME. Biodegradable polymeric nanoparticles as drug carrier :or antitumor agents. In: Juliano RL, editor. Targeted drug delivery. Berlin: Springer; 1991. p. 231.
177. Bodor N, Buchwald P. Barriers to remember: brain-targeting chemical delivery systems and Alzheimer′s disease. Drug Discov Today. 2002;7:766-774
178. Wermuth C. Designing prodrugs and bioprecursors. In: Jolles G, Wooldridge K, editors. Drug design: fact or fantasy? New York (NY): Academic Press; 1984. p. 47-72.
179. Gillies ER, Frechet JMJ. Dendrimers and dendritic polymers in drug delivery. Drug Discov Today. 2005;10:35-43.
180. Lee CC, MacKay JA, Frechet JMJ, Szoka FC. Designing dendrimers for bio- ogical applications. Nat Biotechnol. 2005;12:1517-1526
181. D'Emanuele A, Attwood D. Dendrimer-drug interactions. Adv Drug Deliv Rev. 2005;57:2147-2162
182. Boas U, Heegaard PM. Dendrimers in drug research. Chem Soc Rev. 2004;33:43-63.
183. Huang RQ, Qu YH, Ke WL, Zhu JH, Pei YY, Jiang C. Efficient gene delivery ;argeted to the brain using a transferrin-conjugated polyethylene glycol-modified polyamidoamine dendrimer. FASEB J. 2007;21:1117-1125
184. Wenhao L, Tatsuhiro I, Rieko T. Cell type gene expression, mediated by TFL- 3, a cationic liposomal vector, is controlled by a post-transcription process of delivered plasmid DNA. Int J Pharm. 2004;276:67-74.
185. Pirollo KF, Xu L, Chang EH. Non-viral gene delivery for p53. Curr Opin Mol Ther. 2000;2:168-175
186. Cheng PW. Receptor ligand-facilitated gene transfer: enhancement of lipo- ome mediated gene transfer and expression by transferrin. Hum Gene Ther.1996;7:275-282
187. Yanagihara K, Cheng H, Cheng PW. Effects of epidermal growth factor trans- ferrin and insulin on lipofection efficiency in human lung carcinoma cells. Cancer Gene Ther. 2000;7:59-65.
188. Kono K, Torikoshi Y, Mitsutomi M. Novel gene delivery systems: complexes of fusi- genic polymer-modified liposomes and lipoplexes. Gene Ther. 2001;8:5-12.
189. Xu L, Pirollo KF, Chang EH. Tumor-targeted-p53-gene therapy enhances the efficacy of conventional chemoradiotherapy. J Control Rel. 2001;74:115-128
190. Xu L, Frederik P, Pirollo KF. Self-assembly of a virus-mimicking nanostruc- ture system for efficient tumor-targeted gene delivery. Hum Gene Ther. 2002;13:469-481
191. Seki M, Iwakawa J, Cheng H. p53 and PTEN/MMAC1/TEP1 gene therapy of human prostate PC-3 carcinoma xenograft, using transferrin facilitated lipofection gene delivery strategy. Hum Gene Ther. 2002;13:761-773
192. Rainov NG, Ren H. Gene therapy for human malignant brain tumors. Cancer J. 2003;9:180-188
193. Pardridge WM. Drug and gene delivery to the brain: the vascular route. Neuron. 2002;36:555-558
194. Zhang Y, Boado RJ, Pardridge WM. In vivo knockdown of gene expression in brain cancer with intravenous RNA in adult rats. J Gene Med. 2003;12:1039-1045
195. Weissman IL. Stem cells: units of development, units of regeneration, and units in evolution. Cell. 2000;100:157-168
196. Potten CS, Loeffler M. Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development. 1990;110:1001-1020
197. Dwain I, Xiangpeng Y, Zeng Z, Patricia T, Joh SY. Neural stem cells-a promising potential therapy for brain tumors. Curr Stem Cell Res Ther. 2006;1:79-84.
198. Colleoni F, Torrente Y. The new challenge of stem cell: Brain tumor therapy. Cancer Lett. 2008;272:1-11.
199. Aboody KS, Brown A, Rainov NG. Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proc Natl Acad Sci U S A. 2000;97:12846-12851
200. Ehtesham M, Kabos P, Gutierrez MA. Induction of glioblastoma apoptosis using neural stem cell-mediated delivery of tumor necrosis factor-related apoptosis-inducing ligand. Cancer Res. 2002;62:7170-7174
201. Ehtesham M, Kabos P, Kabosova A, Neuman T, Black KL, Yu JS. The use of interleukin 12-secreting neural stem cells for the treatment of intracranial glioma. Cancer Res. 2002;62:5657-5663
202. Yang SY, Liu H, Zhang JN. Gene therapy of rat malignant gliomas using neural stem cells expressing IL-12 DNA. Cell Biol. 2004;23:381-389
203. Shah K, Bureau E, Kim DE. Glioma therapy and real-time imaging of neural precursor cell migration and tumor regression. Ann Neurol. 2005;57:34-41.
204. Shah K, Tang Y, Breakefield X, Weissleder R. Real-time imaging of TRAIL- induced apoptosis of glioma tumors in vivo. Oncogene. 2003;22:6865-6872
205. Liu Y, Ehtesham M, Samoto K. In situ adenoviral interleukin 12 gene transfer confers potent and long-lasting cytotoxic immunity in glioma. Cancer Gene Ther. 2002;9:9-15.
206. Lasky JL, Liau LM. Targeting stem cells in brain tumors. Technol Cancer Res Treat. 2006;5:251-260
207. Nandi S, Ulasov IV, Tyler MA, Sugihara AQ, Molinero L, Han Y, Zhu ZB, Lesniak MS. Low-dose radiation enhances survivin-mediated virotherapy against malignant glioma stem cells. Cancer Res. 2008;68:5778-5784