The blood-brain barrier: Bottleneck in brain drug development

NeuroRx

Volumn 2, Issue 1, 2005, Pages 3-14

  Pardridge, William M ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Biological transport; Blood brain barrier; Drug targeting; Endothelium; Neurotherapeutics

Indexed keywords

ALCOHOL; AMINO ACID TRANSPORTER; AMYLOID; BRADYKININ; BRAIN DERIVED NEUROTROPHIC FACTOR; DIMETHYL SULFOXIDE; EPIDERMAL GROWTH FACTOR; ETOPOSIDE; FIBROBLAST GROWTH FACTOR 2; GLUCOSE TRANSPORTER 1; GLYCOPROTEIN P; HISTAMINE; HYDROGEN; IMMUNOGLOBULIN G; IMMUNOLIPOSOME; KYOTORPHIN; MELPHALAN; NUCLEOSIDE TRANSPORTER; PEPTIDE NUCLEIC ACID; PLASMID DNA; POLYSORBATE 80; VASOACTIVE INTESTINAL POLYPEPTIDE;

ACTIVE TRANSPORT; ALZHEIMER DISEASE; AREA UNDER THE CURVE; BLOOD BRAIN BARRIER; BRAIN CAPILLARY; BRAIN CELL; CAPILLARY ENDOTHELIUM; CELL MEMBRANE; CENTRAL NERVOUS SYSTEM DISEASE; CEREBROSPINAL FLUID; CYTOLOGY; DRUG DELIVERY SYSTEM; DRUG DIFFUSION; DRUG METABOLISM; DRUG UPTAKE; HYDROGEN BOND; LIPID SOLUBILITY; MOLECULAR DYNAMICS; MOLECULAR SIZE; MOLECULAR WEIGHT; NEUROSCIENCE; NONHUMAN; NONVIRAL GENE DELIVERY SYSTEM; PREDICTION; PROTEIN TRANSPORT; REVIEW; WHITE MATTER;

EID: 12344273726     PISSN: 15455343     EISSN: 15455351     Source Type: Journal    
DOI: 10.1602/neurorx.2.1.3     Document Type: Article

References (80)

1. Pardridge WM. Brain drug targeting: the future of brain drug development. Cambridge, UK: Cambridge University Press, 2001.
2. Lloyd K, Hornykiewicz O. Parkinson's disease activity of l-dopa decarboxylase in discrete brain regions. Science 170:1212-1213, 1970.
3. Zivadinov R, Zorzon M, Tommasi MA, Nasuelli D, Bernardi M, Monti-Bragadin L, et al. A longitudinal study of quality of life and side effects in patients with multiple sclerosis treated with interferon β-1a. J Neurol Sci 216:113-118, 2003.
4. Antinori A, Cingolani A, Giancola ML, Forbici F, De Luca A, Perno CF. Clinical implications of HIV-1 drug resistance in the neurological compartment. Scand J Infect Dis Suppl [35 Suppl] 106:41-44, 2003.
5. Kandanearatchi A, Williams B, Everall IP. Assessing the efficacy of highly active antiretroviral therapy in the brain. Brain Pathol 13:104-110, 2003.
6. Ghose AK, Viswanadhan VN, Wendoloski JJ. A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. J Comb Chem 1:55-68, 1999.
7. Lipinski CA. Drug-like properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Methods 44:235-249, 2000.
8. Fischer H, Gottschlich R, Seelig A. Blood-brain barrier permeation molecular parameters governing passive diffusion. J Membr Biol 165:201-211, 1998.
9. Lieb WR, Stein WD. NonStokesian nature of transverse diffusion within human red cell membranes. J Membr Biol 92:111-119, 1986.
10. Trauble H. The movement of molecules across lipid membranes: a molecular theory. J Membrane Biol 4:193-208, 1971.
11. Pardridge WM, Mietus LJ. Transport of steroid hormones through the rat blood-brain barrier. Primary role of albumin-bound hormone. J Clin Invest 64:145-154, 1979.
12. Lundquist S, Renftel M. The use of in vitro cell culture models for mechanistic studies and as permeability screens for the blood-brain barrier in the pharmaceutical industry-background and current status in the drug discovery process. Vasc Pharmacol 38:355-364, 2002.
13. Fung LK, Shin M, Tyler B, Brem H, Saltzman WM. Chemotherapeutic drugs released from polymers distribution of 1,3-bis(2-chloroethyl)-1-nitrosourea in the rat brain. Pharm Res 13:671-682, 1996.
14. Blasberg RG, Patlak C, Fenstermacher JD. Intrathecal chemotherapy brain tissue profiles after ventriculocisternal perfusion. J Pharmacol Exp Ther 195:73-83, 1975.
15. Krewson CE, Klarman ML, Saltzman WM. Distribution of nerve growth factor following direct delivery to brain interstitium. Brain Res 680:196-206, 1995.
16. Yan Q, Matheson C, Sun J, Radeke MJ, Feinstein SC, Miller JA. Distribution of intracerebral ventricularly administered neurotrophins in rat brain and its correlation with trk receptor expression. Exp Neurol 127:23-36, 1994.
17. Christy NP, Fishman RA. Studies of the blood-cerebrospinal fluid barrier to cortisol in the dog. J Clin Invest 40:1997-2006, 1961.
18. Billiau A, Heremans H, Ververken D, van Damme J, Carton H, de Somer P. Tissue distribution of human interferons after exogenous administration in rabbits, monkeys, and mice. Arch Virol 68:19-25, 1981.
19. Voges J, Reszka R, Gossmann A, Dittmar C, Richter R, Garlip G, et al. Imaging-guided convection-enhanced delivery and gene therapy of glioblastoma. Ann Neurol 54:479-487, 2003.
20. Ai Y, Markesbery W, Zhang Z, Grondin R, Elseberry D, Gerhardt GA, et al. Intraputamenal infusion of GDNF in aged rhesus monkeys distribution and dopaminergic effects. J Comp Neurol 461:250-261, 2003.
21. Zunkeler B, Carson RE, Olson J, Blasberg RG, DeVroom H, Lutz RJ, et al. Quantification and pharmacokinetics of blood-brain barrier disruption in humans. J Neurosurg 85:1056-1065, 1996.
22. Lossinsky AS, Vorbrodt AW, Wisniewski HM. Scanning and transmission electron microscopic studies of microvascular pathology in the osmotically impaired blood-brain barrier. J Neurocytol 24:795-806, 1995.
23. Salahuddin TS, Johansson BB, Kalimo H, Olsson Y. Structural changes in the rat brain after carotid infusions of hyperosmolar solutions. Acta Neuropathol 77:5-13
24. Neuwelt EA, Rapoport SI. Modification of the blood-brain barrier in the chemotherapy of malignant brain tumors. Fed Proc 43:214-219, 1984.
25. Doolittle ND, Petrillo A, Bell S, Cummings P, Eriksen S. Blood-brain barrier disruption for the treatment of malignant brain tumors The National Program. J Neurosci Nurs 30:81-90, 1998.
26. Nadal A, Fuentes E, Pastor J, McNaughton PA. Plasma albumin is a potent trigger of calcium signals and DNA synthesis in astrocytes. Proc Natl Acad Sci USA 92:1426-1430, 1995.
27. Hanig JP, Morrison JM Jr, Krop S. Ethanol enhancement of blood-brain barrier permeability to catecholamines in chicks. Eur J Pharmacol 18:79-82, 1972.
28. Broadwell RD, Salcman M, Kaplan RS. Morphologic effect of dimethyl sulfoxide on the blood-brain barrier. Science 217:164-166, 1982.
29. Saija A, Princi P, Trombetta D, Lanza M, De Pasquale A. Changes in the permeability of the blood-brain barrier following sodium dodecyl sulphate administration in the rat. Exp Brain Res 115:546-551, 1997.
30. Azmin MN, Stuart JF, Florence AT. The distribution and elimination of methotrexate in mouse blood and brain after concurrent administration of polysorbate 80. Cancer Chemother Pharmacol 14:238-242, 1985.
31. Sakane T, Tanaka C, Yamamoto A, Hashida M, Sezaki H, Ueda H, et al. The effect of polysorbate 80 on brain uptake and analgesic effect of D-kyotorphin. Int J Pharm 57:77-83, 1989.
32. Rabchevsky AG, Degos JD, Dreyfus PA. Peripheral injections of Freund's adjuvant in mice provoke leakage of serum proteins through the blood-brain barrier without inducing reactive gliosis. Brain Res 832:84-96, 1999.
33. Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H, Guido T, et al. Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400:173-177, 1999.
34. Kristensson K, Olsson Y. Uptake of exogenous proteins in mouse olfactory cells. Acta Neuropathol (Berl) 19:145-154, 1971.
35. Merkus P, Guchelaar HJ, Bosch DA, Merkus FW. Direct access of drugs to the human brain after intranasal drug administration? Neurology 60:1669-1671, 2003.
36. Born J, Lange T, Kern W, McGregor GP, Bickel U, Fehm HL. Sniffing neuropeptides a transnasal approach to the human brain. Nat Neurosci 5:514-516, 2002.
37. Thorne RG, Emory CR, Ala TA, Frey WH 2nd. Quantitative analysis of the olfactory pathway for drug delivery to the brain. Brain Res 692:278-282, 1995.
38. Bar T. The vascular system of the cerebral cortex. Adv Anat Embryol Cell Biol 59:I-VI, 1-62, 1980.
39. Jaeger CB, Blight AR. Spinal cord compression injury in guinea pigs structural changes of endothelium and its perivascular cell associations after blood-brain barrier breakdown and repair. Exp Neurol 144:381-399, 1997.
40. Pardridge WM, Oldendorf WH. Kinetics of blood-brain barrier transport of hexoses. Biochim Biophys Acta 382:377-392, 1975.
41. Enerson BE, Drewes LR. Molecular features, regulation, and function of monocarboxylate transporters implications for drug delivery. J Pharm Sci 92:1531-1544, 2003.
42. Boado RJ, Li JY, Nagaya M, Zhang C, Pardridge WM. Selective expression of the large neutral amino acid transporter at the blood-brain barrier. Proc Natl Acad Sci USA 96:12079-12084, 1999.
43. Smith QR, Stoll J. Blood-brain barrier amino acid transport. Introduction to the blood-brain barrier: methodology and pathology. Cambridge, UK: Cambridge University Press, 1998.
44. Cornford EM, Braun LD, Oldendorf WH. Carrier mediated blood-brain barrier transport of choline and certain choline analogs. J Neurochem 30:299-308, 1978.
45. Allen DD, Smith QR. Characterization of the blood-brain barrier choline transporter using the in situ rat brain perfusion technique. J Neurochem 76:1032-1041, 2001.
46. Cornford EM, Oldendorf WH. Independent blood-brain barrier transport systems for nucleic acid precursors. Biochim Biophys Acta 394:211-219, 1975.
47. Li JY, Boado RJ, Pardridge WM. Cloned blood-brain barrier adenosine transporter is identical to the rat concentrative Na+ nucleoside cotransporter CNT2. J Cereb Blood Flow Metab 21:929-936, 2001.
48. Pardridge WM, Yoshikawa T, Kang Y-L, Miller LP. Blood-brain barrier transport and brain metabolism of adenosine and adenosine analogs. J Pharmacol Exp Ther 268:14-18, 1994.
49. Zhang Y, Pardridge WM. Rapid transferrin efflux from brain to blood across the blood-brain barrier. J Neurochem 76:1597-1600, 2001.
50. 125I]transferrin through the rat blood-brain barrier. Brain Res 683:164-171, 1995.
51. Zhang Y, Pardridge WM. Mediated efflux of IgG molecules from brain to blood across the blood-brain barrier. J Neuroimmunol 114:168-172, 2001.
52. Schlachetzki F, Zhu C, Pardridge WM. Expression of the neonatal Fc receptor (FcRn) at the blood-brain barrier. J Neurochem 81:203-206, 2002.
53. Triguero D, Buciak J, Pardridge WM. Capillary depletion method for quantification of blood-brain barrier transport of circulating peptides and plasma proteins. J Neurochem 54:1882-1888, 1990.
54. Wu D, Pardridge WM. Central nervous system pharmacologic effect in conscious rats after intravenous injection of a biotinylated vasoactive intestinal peptide analog coupled to a blood-brain barrier drug delivery system. J Pharmacol Exp Ther 279:77-83, 1996.
55. Wu D, Pardridge WM. Neuroprotection with noninvasive neurotrophin delivery to the brain. Proc Natl Acad Sci USA 96:254-259, 1999.
56. Zhang Y, Pardridge WM. Conjugation of brain-derived neurotrophic factor to a blood-brain barrier drug targeting system enables neuroprotection in regional brain ischemia following intravenous injection of the neurotrophin. Brain Res 889:49-56, 2001.
57. Zhang Y, Pardridge WM. Neuroprotection in transient focal brain ischemia after delayed intravenous administration of brain-derived neurotrophic factor conjugated to a blood-brain barrier drug targeting system. Stroke 32:1378-1384, 2001.
58. Song BW, Vinters HV, Wu D, Pardridge WM. Enhanced neuroprotective effects of basic fibroblast growth factor in regional brain ischemia after conjugation to a blood-brain barrier delivery vector. J Pharmacol Exp Ther 301:605-610, 2002.
59. Kurihara A, Pardridge WM. Imaging brain tumors by targeting peptide radiopharmaceuticals through the blood-brain barrier. Cancer Res 59:6159-6163, 1999.
60. Lee HJ, Zhang Y, Zhu C, Duff K, Pardridge WM. Imaging brain amyloid of Alzheimer disease in vivo in transgenic mice with an Aβ peptide radiopharmaceutical. J Cereb Blood Flow Metab 22:223-231, 2002.
61. Lee HJ, Boado RJ, Braasch DA, Corey DR, Pardridge WM. Imaging gene expression in the brain in vivo in a transgenic mouse model of Huntington' s disease with an antisense radiopharmaceutical and drug-targeting technology. J Nucl Med 43:948-956, 2002.
62. 111-peptide nucleic acid antisense radiopharmaceuticals and brain drug-targeting technology. J Nucl Med 10:1766-1775, 2004.
63. Huwyler J, Wu D, Pardridge WM. Brain drug delivery of small molecules using immunoliposomes. Proc Natl Acad Sci USA 93: 14164-14169, 1996.
64. Olivier JC, Huertas R, Lee HJ, Calon F, Pardridge WM. Synthesis of pegylated immunonanoparticles. Pharm Res 19:1137-1143, 2002.
65. Shi N, Zhang Y, Zhu C, Boado RJ, Pardridge WM. Brain-specific expression of an exogenous gene after i.v. administration. Proc Natl Acad Sci USA 98:12754-12759, 2001.
66. Zhang Y, Schlachetzki F, Zhang YF, Boado RJ, Pardridge WM. Normalization of striatal tyrosine hydroxylase and reversal of motor impairment in experimental parkinsonism with intravenous nonviral gene therapy and a brain-specific promoter. Hum Gene Ther 15:339-350, 2004.
67. Zhang Y, Zhu C, Pardridge WM. Antisense gene therapy of brain cancer with an artificial virus gene delivery system. Mol Ther 6:67-72, 2002.
68. Zhang Y, Schlachetzki F, Pardridge WM. Global non-viral gene transfer to the primate brain following intravenous administration. Mol Ther 7:11-18, 2003.
69. Zhang Y, Boado RJ, Pardridge WM. In vivo knockdown of gene expression in brain cancer with intravenous RNAi in adult rats. J Gene Med 5:1039-1045, 2003.
70. Zhang Y, Bryant J, Zhang YF, Charles A, Boado RJ, Pardridge WM. Intravenous RNAi gene therapy targeting the human EGF receptor prolongs survival in intra-cranial brain cancer. Clin Cancer Res 10:3667-3677.
71. Pardridge WM. Why is the global CNS pharmaceutical market so under-penetrated? Drug Discov Today 7:5-7, 2002.
72. Matsukado K, Sugita M, Black KL. Intracarotid low dose bradykinin infusion selectively increases tumor permeability through activation of bradykinin B2 receptors in malignant gliomas. Brain Res 792:10-15, 1998.
73. Spigelman MK, Zappulla RA, Goldberg JD, Goldsmith SJ, Marotta D, Malis LI, et al. Effect of intracarotid etoposide on opening the blood-brain barrier. Cancer Drug Deliv 1:207-211, 1984.
74. Cornford EM, Young D, Paxton JW, Finlay GJ, Wilson WR, Pardridge WM. Melphalan penetration of the blood-brain barrier via the neutral amino acid transporter in tumor-bearing brain. Cancer Res 52:138-143, 1992.
75. Hynynen K, McDannold N, Vykhodtseva N, Jolesz FA. Noninvasive MR imaging-guided focal opening of the blood-brain barrier in rabbits. Radiology 220:640-646, 2001.
76. Bolton SJ, Anthony DC, Perry VH. Loss of the tight junction proteins occludin and zonula occludens-1 from cerebral vascular endothelium during neutrophil-induced blood-brain barrier breakdown in vivo. Neuroscience 86:1245-1257, 1998.
77. Anthony D, Dempster R, Fearn S, Clements J, Wells G, Perry VH, et al. CXC chemokines generate age-related increases in neutrophil-mediated brain inflammation and blood-brain barrier breakdown. Curr Biol 8:923-926, 1998.
78. Oldendorf WH, Stoller BE, Tishler TA, Williams JL, Oldendorf SZ. Transient blood-brain barrier passage of polar compounds at low pH. Am J Physiol (Lond) 267:H2229-H2236, 1994.
79. Oztas B, Kucuk M. Intracarotid hypothermic saline infusion a new method for reversible blood-brain barrier disruption in anesthetized rats. Neurosci Lett 190:203-206, 1995.
80. Sztriha L, Betz AL. Oleic acid reversibly opens the blood-brain barrier. Brain Res 550:257-262, 1991.