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Cited by 219Barrier Structure and Function StudiesDrug Transport and Resistance MechanismsNanoparticle-Based Drug Delivery

A Historical Review of Brain Drug Delivery

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Pardridge, William M.·2022·Pharmaceutics
DOI 10.3390/pharmaceutics14061283PMC PMC9229021
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Abstract

The history of brain drug delivery is reviewed beginning with the first demonstration, in 1914, that a drug for syphilis, salvarsan, did not enter the brain, due to the presence of a blood–brain barrier (BBB). Owing to restricted transport across the BBB, FDA-approved drugs for the CNS have been generally limited to lipid-soluble small molecules. Drugs that do not cross the BBB can be re-engineered for transport on endogenous BBB carrier-mediated transport and receptor-mediated transport systems, which were identified during the 1970s–1980s. By the 1990s, a multitude of brain drug delivery technologies emerged, including trans-cranial delivery, CSF delivery, BBB disruption, lipid carriers, prodrugs, stem cells, exosomes, nanoparticles, gene therapy, and biologics. The advantages and limitations of each of these brain drug delivery technologies are critically reviewed.

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  • Disrupting the blood-brain barrier by opening tight junctions using non-invasive physical methods such as infusion of noxious agents or injection of microbubbles followed by sonication is another strategy.

    “Disrupting the BBB, which consists of opening the TJs of the brain using non-invasive physical methods like infusion of noxious agents (e.g., bradykinin that induces vasodilation) or injection of microbubbles (MBs) (small vehicles filled with gas), followed by sonication (e.g., focused ultrasound (FUS) sonication), is another strategy [16].”

    From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [16]

    The Introduction describes BBB disruption by intra-arterial infusion of noxious agents or intravenous microbubble injection followed by brain sonication. Sections 4.2 and 4.3 support tight-junction opening with focused ultrasound and microbubbles. But §4.3 describes these approaches as requiring operating-room treatment, not as non-invasive; §4.1 discusses bradykinin and its analogue as biochemical agents rather than non-invasive physical methods. Page numbers were not provided. (LLM, conf=0.88)

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  1. [1]Pardridge W.M. The blood-brain barrier: Bottleneck in brain drug development NeuroRX 2005 2 3 14 10.1602/neurorx.2.1.3 15717053 PMC539316 · DOI · Paper page
  2. [2]Pardridge W.M. Oldendorf W.H. Cancilla P. Frank H.J. Blood-brain barrier: Interface between internal medicine and the brain Ann. Intern. Med. 1986 105 82 95 10.7326/0003-4819-105-1-82 2872846 · DOI
  3. [3]Brightman M.W. Reese T.S. Junctions between intimately apposed cell membranes in the vertebrate brain J. Cell Biol. 1969 40 648 677 10.1083/jcb.40.3.648 5765759 PMC2107650 · DOI
  4. [4]Reese T.S. Karnovsky M.J. Fine structural localization of a blood-brain barrier to exogenous peroxidase J. Cell Biol. 1967 34 207 217 10.1083/jcb.34.1.207 6033532 PMC2107213 · DOI · Paper page
  5. [5]Maxwell D.S. Pease D.C. The electron microscopy of the choroid plexus J. Cell Biol. 1956 2 467 474 10.1083/jcb.2.4.467 PMC2229709 13357511 · DOI
  6. [6]Zeuthen T. Wright E.M. Epithelial potassium transport: Tracer and electrophysiological studies in choroid plexus J. Membr. Biol. 1981 60 105 128 10.1007/BF01870414 6973025 · DOI
  7. [7]Butt A.M. Jones H.C. Abbott N.J. Electrical resistance across the blood-brain barrier in anaesthetized rats: A developmental study J. Physiol. 1990 429 47 62 10.1113/jphysiol.1990.sp018243 2277354 PMC1181686 · DOI · Paper page
  8. [8]Allt G. Lawrenson J.G. Is the pial microvessel a good model for blood-brain barrier studies? Brain Res. Rev. 1997 24 67 76 10.1016/S0165-0173(97)00011-8 9233542 · DOI
  9. [10]Smith Q.R. Rapoport S.I. Cerebrovascular permeability coefficients to sodium, potassium, and chloride J. Neurochem. 1986 46 1732 1742 10.1111/j.1471-4159.1986.tb08491.x 3084708 · DOI · Paper page
  10. [12]Reiber H. Proteins in cerebrospinal fluid and blood: Barriers, CSF flow rate and source-related dynamics Restor. Neurol. Neurosci. 2003 21 79 96 14530572
  11. [13]Yadav D.B. Maloney J.A. Wildsmith K.R. Fuji R.N. Meilandt W.J. Solanoy H. Lu Y. Peng K. Wilson B. Chan P. Widespread brain distribution and activity following i.c.v. infusion of anti-beta-secretase (BACE1) in nonhuman primates Br. J. Pharmacol. 2017 174 4173 4185 10.1111/bph.14021 28859225 PMC5659992 · DOI · Paper page
  12. [14]Duvernoy H.M. Delon S. Vannson J.L. Cortical blood vessels of the human brain Brain Res. Bull. 1981 7 519 579 10.1016/0361-9230(81)90007-1 7317796 · DOI
  13. [15]Pardridge W.M. Treatment of Alzheimer’s Disease and Blood-Brain Barrier Drug Delivery Pharmaceuticals 2020 13 394 10.3390/ph13110394 PMC7697739 33207605 · DOI
  14. [16]Kutuzov N. Flyvbjerg H. Lauritzen M. Contributions of the glycocalyx, endothelium, and extravascular compartment to the blood-brain barrier Proc. Natl. Acad. Sci. USA 2018 115 E9429 E9438 10.1073/pnas.1802155115 30217895 PMC6176561 · DOI
  15. [17]Cornford E.M. Hyman S. Cornford M.E. Landaw E.M. Delgado-Escueta A.V. Interictal seizure resections show two configurations of endothelial Glut1 glucose transporter in the human blood-brain barrier J. Cereb. Blood Flow Metab. 1998 18 26 42 10.1097/00004647-199801000-00003 9428303 · DOI
  16. [18]Vogel J. Sperandio M. Pries A.R. Linderkamp O. Gaehtgens P. Kuschinsky W. Influence of the endothelial glycocalyx on cerebral blood flow in mice J. Cereb. Blood Flow Metab. 2000 20 1571 1578 10.1097/00004647-200011000-00007 11083232 · DOI
  17. [19]Yoon J.H. Lee E.S. Jeong Y. In vivo Imaging of the Cerebral Endothelial Glycocalyx in Mice J. Vasc. Res. 2017 54 59 67 10.1159/000457799 28365703 · DOI
  18. [20]Ando Y. Okada H. Takemura G. Suzuki K. Takada C. Tomita H. Zaikokuji R. Hotta Y. Miyazaki N. Yano H. Brain-Specific Ultrastructure of Capillary Endothelial Glycocalyx and Its Possible Contribution for Blood Brain Barrier Sci. Rep. 2018 8 17523 10.1038/s41598-018-35976-2 30504908 PMC6269538 · DOI
  19. [21]Thomsen M.S. Routhe L.J. Moos T. The vascular basement membrane in the healthy and pathological brain J. Cereb. Blood Flow Metab. 2017 37 3300 3317 10.1177/0271678X17722436 28753105 PMC5624399 · DOI
  20. [23]Liddelow S.A. Fluids and barriers of the CNS: A historical viewpoint Fluids Barriers CNS 2011 8 2 10.1186/2045-8118-8-2 21349150 PMC3039834 · DOI
  21. [24]Thakur J.D. Sonig A. Chittiboina P. Khan I.S. Wadhwa R. Nanda A. Humphrey Ridley (1653-1708): 17th century evolution in neuroanatomy and selective cerebrovascular injections for cadaver dissection Neurosurg. Focus 2012 33 E3 10.3171/2012.6.FOCUS12139 22853834 · DOI
  22. [25]Marcinowski F. Max Lewandowsky (1876–1918) J. Neurol. 2020 267 1223 1224 10.1007/s00415-019-09393-y · DOI
  23. [26]Mott F.W. The Late Professor Edwin Goldmann’s Investigations on the Central Nervous System by Vital Staining Br. Med. J. 1913 2 871 873 20766814 PMC2345891
  24. [27]McIntosh J. Fildes P. The factors which govern the penetration of arsenic (salvarsan) and aniline dyes into the brain and their bearing upon the treatment of cerebral syphilis Brain 1916 39 478 483 10.1093/brain/39.3-4.478 · DOI
  25. [28]Vein A.A. Science and fate: Lina Stern (1878–1968), a neurophysiologist and biochemist J. Hist. Neurosci. 2008 17 195 206 10.1080/09647040601138478 18421636 · DOI
  26. [29]Broman T. The possibilities of the passage of substances from the blood to the central nervous system Acta Psychiatr. Scand. 1941 16 1 25 10.1111/j.1600-0447.1941.tb07398.x · DOI
  27. [30]Friedemann U. Blood-brain barrier Physiol. Rev. 1942 22 125 142 10.1152/physrev.1942.22.2.125 · DOI
  28. [31]Krough A. The active and passive exchange of inorganic ions through the surface of living cells and through living membranes generally Proc. R. Soc. London Ser. B 1946 133 140 200 10.1098/rspb.1946.0008 21014293 · DOI
  29. [32]Hassin G.B. Cerebrospinal fluid, its origin, nature and function J. Neuropathol. Exp. Neurol. 1948 7 172 181 10.1097/00005072-194804000-00005 18915133 · DOI
  30. [33]Dobbing J. The blood-brain barrier Physiol. Rev. 1961 41 130 188 10.1152/physrev.1961.41.1.130 13723231 · DOI
  31. [34]Zheng W. Ghersi-Egea J.F. Brain Barrier Systems Play No Small Roles in Toxicant-induced Brain Disorders Toxicol. Sci. 2020 175 147 148 10.1093/toxsci/kfaa053 32298456 PMC7253204 · DOI
  32. [35]Ehrlich P. Address in Pathology, ON CHEMIOTHERAPY: Delivered before the Seventeenth International Congress of Medicine Br. Med. J. 1913 2 353 359 10.1136/bmj.2.2746.353 20766753 PMC2345634 · DOI
  33. [36]Lloyd N.C. Morgan H.W. Nicholson B.K. Ronimus R.S. The composition of Ehrlich’s salvarsan: Resolution of a century-old debate Angew. Chem. Int. Ed. Engl. 2005 44 941 944 10.1002/anie.200461471 15624113 · DOI
  34. [37]Bosch F. Rosich L. The contributions of Paul Ehrlich to pharmacology: A tribute on the occasion of the centenary of his Nobel Prize Pharmacology 2008 82 171 179 10.1159/000149583 18679046 PMC2790789 · DOI
  35. [38]Wile U.J. Experimental Syphilis in the Rabbit Produced by the Brain Substance of the Living Paretic J. Exp. Med. 1916 23 199 202 10.1084/jem.23.2.199 19867978 PMC2125396 · DOI
  36. [39]McIntosh J. Fildes P. The fixation of arsenic by the brain after intravenous injection of salvarsan Proc. R. Soc. London Ser. B 1914 88 320 326 10.1098/rspb.1914.0077 · DOI
  37. [40]Winkelman N.W. Jr. Chlorpromazine in the treatment of neuropsychiatric disorders J. Am. Med. Assoc. 1954 155 18 21 10.1001/jama.1954.03690190024007 13151880 · DOI
  38. [41]Barsa J.A. Combination drug therapy in psychiatry Am. J. Psychiatry 1960 117 448 449 10.1176/ajp.117.5.448 14448489 · DOI
  39. [42]Oldendorf W.H. Hyman S. Braun L. Oldendorf S.Z. Blood-brain barrier: Penetration of morphine, codeine, heroin, and methadone after carotid injection Science 1972 178 984 986 10.1126/science.178.4064.984 5084666 · DOI
  40. [43]Shanbrom E. Miller S. Fairbanks V.F. Intrathecal administration of amethopterin in leukemic encephalopathy of young adults N. Engl. J. Med. 1961 265 169 171 10.1056/NEJM196107272650404 13750662 · DOI
  41. [44]Ommaya A.K. Subcutaneous reservoir and pump for sterile access to ventricular cerebrospinal fluid Lancet 1963 2 983 984 10.1016/S0140-6736(63)90681-0 14059058 · DOI
  42. [45]Hornykiewicz O. Dopamine (3-hydroxytyramine) and brain function Pharmacol. Rev. 1966 18 925 964 5328389
  43. [46]Wade L.A. Katzman R. Synthetic amino acids and the nature of L-DOPA transport at the blood-brain barrier J. Neurochem. 1975 25 837 842 10.1111/j.1471-4159.1975.tb04415.x 1206400 · DOI
  44. [47]Oldendorf W.H. Measurement of brain uptake of radiolabeled substances using a tritiated water internal standard Brain Res. 1970 24 372 376 10.1016/0006-8993(70)90123-X 5490302 · DOI
  45. [48]Oldendorf W.H. Brain uptake of radiolabeled amino acids, amines, and hexoses after arterial injection Am. J. Physiol. 1971 221 1629 1639 10.1152/ajplegacy.1971.221.6.1629 5124307 · DOI
  46. [49]Neuwelt E.A. Maravilla K.R. Frenkel E.P. Rapaport S.I. Hill S.A. Barnett P.A. Osmotic blood-brain barrier disruption. Computerized tomographic monitoring of chemotherapeutic agent delivery J. Clin. Investig. 1979 64 684 688 10.1172/JCI109509 457877 PMC372166 · DOI
  47. [50]Anand Kumar T.C. David G.F. Sankaranarayanan A. Puri V. Sundram K.R. Pharmacokinetics of progesterone after its administration to ovariectomized rhesus monkeys by injection, infusion, or nasal spraying Proc. Natl. Acad. Sci. USA 1982 79 4185 4189 10.1073/pnas.79.13.4185 6955795 PMC346602 · DOI
  48. [51]Brem H. Tamargo R.J. Olivi A. Pinn M. Weingart J.D. Wharam M. Epstein J.I. Biodegradable polymers for controlled delivery of chemotherapy with and without radiation therapy in the monkey brain J. Neurosurg. 1994 80 283 290 10.3171/jns.1994.80.2.0283 8283268 · DOI
  49. [52]Frim D.M. Uhler T.A. Galpern W.R. Beal M.F. Breakefield X.O. Isacson O. Implanted fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevent 1-methyl-4-phenylpyridinium toxicity to dopaminergic neurons in the rat Proc. Natl. Acad. Sci. USA 1994 91 5104 5108 10.1073/pnas.91.11.5104 8197193 PMC43940 · DOI · Paper page
  50. [53]Morrison P.F. Laske D.W. Bobo H. Oldfield E.H. Dedrick R.L. High-flow microinfusion: Tissue penetration and pharmacodynamics Am. J. Physiol. 1994 266 R292 R305 10.1152/ajpregu.1994.266.1.R292 8304553 · DOI
  51. [54]Kumagai A.K. Eisenberg J.B. Pardridge W.M. Absorptive-mediated endocytosis of cationized albumin and a beta-endorphin-cationized albumin chimeric peptide by isolated brain capillaries. Model system of blood-brain barrier transport J. Biol. Chem. 1987 262 15214 15219 10.1016/S0021-9258(18)48160-4 2959663 · DOI
  52. [55]Fawell S. Seery J. Daikh Y. Moore C. Chen L.L. Pepinsky B. Barsoum J. Tat-mediated delivery of heterologous proteins into cells Proc. Natl. Acad. Sci. USA 1994 91 664 668 10.1073/pnas.91.2.664 8290579 PMC43009 · DOI
  53. [56]Bolton S.J. Jones D.N. Darker J.G. Eggleston D.S. Hunter A.J. Walsh F.S. Cellular uptake and spread of the cell-permeable peptide penetratin in adult rat brain Eur. J. Neurosci. 2000 12 2847 2855 10.1046/j.1460-9568.2000.00171.x 10971627 · DOI
  54. [57]Shashoua V.E. Hesse G.W. N-docosahexaenoyl, 3 hydroxytyramine: A dopaminergic compound that penetrates the blood-brain barrier and suppresses appetite Life Sci. 1996 58 1347 1357 10.1016/0024-3205(96)00101-4 8614292 · DOI
  55. [58]Pardridge W.M. Receptor-mediated peptide transport through the blood-brain barrier Endocr. Rev. 1986 7 314 330 10.1210/edrv-7-3-314 3017689 · DOI
  56. [59]Pardridge W.M. Buciak J.L. Friden P.M. Selective transport of an anti-transferrin receptor antibody through the blood-brain barrier in vivo J. Pharmacol. Exp. Ther. 1991 259 66 70 1920136
  57. [60]Friden P.M. Walus L.R. Musso G.F. Taylor M.A. Malfroy B. Starzyk R.M. Anti-transferrin receptor antibody and antibody-drug conjugates cross the blood-brain barrier Proc. Natl. Acad. Sci. USA 1991 88 4771 4775 10.1073/pnas.88.11.4771 2052557 PMC51748 · DOI
  58. [61]Pardridge W.M. Kang Y.S. Buciak J.L. Yang J. Human insulin receptor monoclonal antibody undergoes high affinity binding to human brain capillaries in vitro and rapid transcytosis through the blood-brain barrier in vivo in the primate Pharm. Res. 1995 12 807 816 10.1023/A:1016244500596 7667183 · DOI
  59. [62]Cordon-Cardo C. O’Brien J.P. Casals D. Rittman-Grauer L. Biedler J.L. Melamed M.R. Bertino J.R. Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites Proc. Natl. Acad. Sci. USA 1989 86 695 698 10.1073/pnas.86.2.695 2563168 PMC286540 · DOI
  60. [63]Shibata S. Ochi A. Mori K. Liposomes as carriers of cisplatin into the central nervous system--experiments with 9L gliomas in rats Neurol. Med.-Chir. 1990 30 242 245 10.2176/nmc.30.242 1696693 · DOI
  61. [64]Kreuter J. Alyautdin R.N. Kharkevich D.A. Ivanov A.A. Passage of peptides through the blood-brain barrier with colloidal polymer particles (nanoparticles) Brain Res. 1995 674 171 174 10.1016/0006-8993(95)00023-J 7773690 · DOI
  62. [65]Nigavekar S.S. Sung L.Y. Llanes M. El-Jawahri A. Lawrence T.S. Becker C.W. Balogh L. Khan M.K. 3H dendrimer nanoparticle organ/tumor distribution Pharm. Res. 2004 21 476 483 10.1023/B:PHAM.0000019302.26097.cc 15070099 · DOI
  63. [66]Hynynen K. McDannold N. Vykhodtseva N. Jolesz F.A. Noninvasive MR imaging-guided focal opening of the blood-brain barrier in rabbits Radiology 2001 220 640 646 10.1148/radiol.2202001804 11526261 · DOI
  64. [67]Alvarez-Erviti L. Seow Y. Yin H. Betts C. Lakhal S. Wood M.J. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes Nat. Biotechnol. 2011 29 341 345 10.1038/nbt.1807 21423189 · DOI · Paper page
  65. [69]Chodobski A. Szmydynger-Chodobska J. Johanson C.E. Vasopressin mediates the inhibitory effect of central angiotensin II on cerebrospinal fluid formation Eur. J. Pharmacol. 1998 347 205 209 10.1016/S0014-2999(98)00229-5 9653883 · DOI
  66. [72]Wagner H.J. Pilgrim C. Brandl J. Penetration and removal of horseradish peroxidase injected into the cerebrospinal fluid: Role of cerebral perivascular spaces, endothelium and microglia Acta Neuropathol. 1974 27 299 315 10.1007/BF00690695 4366438 · DOI
  67. [73]Rennels M.L. Gregory T.F. Blaumanis O.R. Fujimoto K. Grady P.A. Evidence for a ‘paravascular’ fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid space Brain Res. 1985 326 47 63 10.1016/0006-8993(85)91383-6 3971148 · DOI · Paper page
  68. [74]Hamezah H.S. Durani L.W. Ibrahim N.F. Yanagisawa D. Kato T. Shiino A. Tanaka S. Damanhuri H.A. Ngah W.Z.W. Tooyama I. Volumetric changes in the aging rat brain and its impact on cognitive and locomotor functions Exp. Gerontol. 2017 99 69 79 10.1016/j.exger.2017.09.008 28918364 · DOI
  69. [75]Przyborowska P. Adamiak Z. Zhalniarovich Y. Quantification of cerebral lateral ventricular volume in cats by low- and high-field MRI J. Feline Med. Surg. 2017 19 1080 1086 10.1177/1098612X16676434 27827800 PMC11110985 · DOI
  70. [76]Hladky S.B. Barrand M.A. The glymphatic hypothesis: The theory and the evidence Fluids Barriers CNS 2022 19 9 10.1186/s12987-021-00282-z 35115036 PMC8815211 · DOI
  71. [77]Wolak D.J. Pizzo M.E. Thorne R.G. Probing the extracellular diffusion of antibodies in brain using in vivo integrative optical imaging and ex vivo fluorescence imaging J. Control. Release 2015 197 78 86 10.1016/j.jconrel.2014.10.034 25449807 PMC4272890 · DOI
  72. [78]Blasberg R.G. Patlak C. Fenstermacher J.D. Intrathecal chemotherapy: Brain tissue profiles after ventriculocisternal perfusion J. Pharmacol. Exp. Ther. 1975 195 73 83 810575
  73. [79]Yan Q. Matheson C. Sun J. Radeke M.J. Feinstein S.C. Miller J.A. Distribution of intracerebral ventricularly administered neurotrophins in rat brain and its correlation with trk receptor expression Exp. Neurol. 1994 127 23 36 10.1006/exnr.1994.1076 8200435 · DOI
  74. [80]Levin V.A. Fenstermacher J.D. Patlak C.S. Sucrose and inulin space measurements of cerebral cortex in four mammalian species Am. J. Physiol. 1970 219 1528 1533 10.1152/ajplegacy.1970.219.5.1528 4990676 · DOI
  75. [81]Stadlbauer A. Salomonowitz E. van der Riet W. Buchfelder M. Ganslandt O. Insight into the patterns of cerebrospinal fluid flow in the human ventricular system using MR velocity mapping Neuroimage 2010 51 42 52 10.1016/j.neuroimage.2010.01.110 20152907 · DOI
  76. [82]Nagaraja T.N. Patel P. Gorski M. Gorevic P.D. Patlak C.S. Fenstermacher J.D. In normal rat, intraventricularly administered insulin-like growth factor-1 is rapidly cleared from CSF with limited distribution into brain Cerebrospinal Fluid Res. 2005 2 5 10.1186/1743-8454-2-5 16045806 PMC1190198 · DOI
  77. [83]Fishman R.A. Christy N.P. Fate of Adrenal Cortical Steroids Following Intrathecal Injection Neurology 1965 15 1 10.1212/WNL.15.1.1 14257825 · DOI
  78. [84]Reed D.J. Woodbury D.M. Kinetics of Movement of Iodide, Sucrose, Inulin and Radio-Iodinated Serum Albumin in the Central Nervous System and Cerebrospinal Fluid of the Rat J. Physiol. 1963 169 816 850 10.1113/jphysiol.1963.sp007298 14103562 PMC1368802 · DOI
  79. [85]Aird R.B. A study of intrathecal, cerebrospinal fluid-to-brain exchange Exp. Neurol. 1984 86 342 358 10.1016/0014-4886(84)90192-4 6548450 · DOI
  80. [86]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. 1981 68 19 25 10.1007/BF01315163 6166278 · DOI
  81. [87]Crawley J.N. Fiske S.M. Durieux C. Derrien M. Roques B.P. Centrally administered cholecystokinin suppresses feeding through a peripheral-type receptor mechanism J. Pharmacol. Exp. Ther. 1991 257 1076 1080 2046021
  82. [88]De Lange E.C. Danhof M. de Boer A.G. Breimer D.D. Critical factors of intracerebral microdialysis as a technique to determine the pharmacokinetics of drugs in rat brain Brain Res. 1994 666 1 8 10.1016/0006-8993(94)90276-3 7889356 · DOI
  83. [89]Kan S.H. Aoyagi-Scharber M. Le S.Q. Vincelette J. Ohmi K. Bullens S. Wendt D.J. Christianson T.M. Tiger P.M. Brown J.R. Delivery of an enzyme-IGFII fusion protein to the mouse brain is therapeutic for mucopolysaccharidosis type IIIB Proc. Natl. Acad. Sci. USA 2014 111 14870 14875 10.1073/pnas.1416660111 25267636 PMC4205671 · DOI
  84. [90]Larson S.M. Carrasquillo J.A. Cheung N.K. Press O.W. Radioimmunotherapy of human tumours Nat. Rev. Cancer 2015 15 347 360 10.1038/nrc3925 25998714 PMC4798425 · DOI
  85. [91]Onofrio B.M. Yaksh T.L. Long-term pain relief produced by intrathecal morphine infusion in 53 patients J. Neurosurg. 1990 72 200 209 10.3171/jns.1990.72.2.0200 1688618 · DOI
  86. [92]Wang D. Tawfik V.L. Corder G. Low S.A. Francois A. Basbaum A.I. Scherrer G. Functional Divergence of Delta and Mu Opioid Receptor Organization in CNS Pain Circuits Neuron 2018 98 90 108.e5 10.1016/j.neuron.2018.03.002 29576387 PMC5896237 · DOI
  87. [93]Jacobs N.W. Maas E.M. Brusse-Keizer M. Rietman H.J.S. Effectiveness and safety of cervical catheter tip placement in intrathecal baclofen treatment of spasticity: A systematic review J. Rehabil. Med. 2021 53 jrm00215 10.2340/16501977-2857 34160624 PMC8638738 · DOI
  88. [94]Fukuhara K. Katafuchi T. Yoshimura M. Effects of baclofen on mechanical noxious and innocuous transmission in the spinal dorsal horn of the adult rat: In vivo patch-clamp analysis Eur. J. Neurosci. 2013 38 3398 3407 10.1111/ejn.12345 23961926 · DOI
  89. [95]Aartsma-Rus A. FDA Approval of Nusinersen for Spinal Muscular Atrophy Makes 2016 the Year of Splice Modulating Oligonucleotides Nucleic Acid. Ther. 2017 27 67 69 10.1089/nat.2017.0665 28346110 · DOI
  90. [97]Shababi M. Lorson C.L. Rudnik-Schoneborn S.S. Spinal muscular atrophy: A motor neuron disorder or a multi-organ disease? J. Anat. 2014 224 15 28 10.1111/joa.12083 23876144 PMC3867883 · DOI
  91. [98]Kulkarni J.A. Witzigmann D. Thomson S.B. Chen S. Leavitt B.R. Cullis P.R. van der Meel R. The current landscape of nucleic acid therapeutics Nat. Nanotechnol. 2021 16 630 643 10.1038/s41565-021-00898-0 34059811 · DOI · Paper page
  92. [99]Muenzer J. Hendriksz C.J. Fan Z. Vijayaraghavan S. Perry V. Santra S. Solanki G.A. Mascelli M.A. Pan L. Wang N. A phase I/II study of intrathecal idursulfase-IT in children with severe mucopolysaccharidosis II Genet. Med. 2016 18 73 81 10.1038/gim.2015.36 25834948 · DOI
  93. [100]Jones S.A. Breen C. Heap F. Rust S. de Ruijter J. Tump E. Marchal J.P. Pan L. Qiu Y. Chung J.K. A phase 1/2 study of intrathecal heparan-N-sulfatase in patients with mucopolysaccharidosis IIIA Mol. Genet. Metab. 2016 118 198 205 10.1016/j.ymgme.2016.05.006 27211612 · DOI
  94. [101]Wijburg F.A. Whitley C.B. Muenzer J. Gasperini S. Del Toro M. Muschol N. Cleary M. Sevin C. Shapiro E. Alexanderian D. A multicenter open-label extension study of intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A Mol. Genet. Metab. 2021 134 175 181 10.1016/j.ymgme.2021.07.001 34247932 · DOI
  95. [102]Shapiro W.R. Young D.F. Mehta B.M. Methotrexate: Distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections N. Engl. J. Med. 1975 293 161 166 10.1056/NEJM197507242930402 806016 · DOI
  96. [103]Rieselbach R.E. Di Chiro G. Freireich E.J. Rall D.P. Subarachnoid distribution of drugs after lumbar injection N. Engl. J. Med. 1962 267 1273 1278 10.1056/NEJM196212202672502 13973811 · DOI
  97. [104]Peyrl A. Chocholous M. Azizi A.A. Czech T. Dorfer C. Mitteregger D. Gojo J. Minichmayr E. Slavc I. Safety of Ommaya reservoirs in children with brain tumors: A 20-year experience with 5472 intraventricular drug administrations in 98 patients J. Neuro-Oncol. 2014 120 139 145 10.1007/s11060-014-1531-1 25017328 · DOI
  98. [105]Gerber N.U. Muller A. Bellut D. Bozinov O. Berger C. Grotzer M.A. Ventricular Catheter Systems with Subcutaneous Reservoirs (Ommaya Reservoirs) in Pediatric Patients with Brain Tumors: Infections and Other Complications Neuropediatrics 2015 46 401 409 10.1055/s-0035-1565271 26479760 · DOI
  99. [106]Hall C.D. Dafni U. Simpson D. Clifford D. Wetherill P.E. Cohen B. McArthur J. Hollander H. Yainnoutsos C. Major E. Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. AIDS Clinical Trials Group 243 Team N. Engl. J. Med. 1998 338 1345 1351 10.1056/NEJM199805073381903 9571254 · DOI
  100. [107]Nutt J.G. Burchiel K.J. Comella C.L. Jankovic J. Lang A.E. Laws E.R. Jr. Lozano A.M. Penn R.D. Simpson R.K. Jr. Stacy M. Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD Neurology 2003 60 69 73 10.1212/WNL.60.1.69 12525720 · DOI
  101. [108]Yamada K. Kinoshita A. Kohmura E. Sakaguchi T. Taguchi J. Kataoka K. Hayakawa T. Basic fibroblast growth factor prevents thalamic degeneration after cortical infarction J. Cereb. Blood Flow Metab. 1991 11 472 478 10.1038/jcbfm.1991.90 2016355 · DOI
  102. [109]Day-Lollini P.A. Stewart G.R. Taylor M.J. Johnson R.M. Chellman G.J. Hyperplastic changes within the leptomeninges of the rat and monkey in response to chronic intracerebroventricular infusion of nerve growth factor Exp. Neurol. 1997 145 24 37 10.1006/exnr.1997.6448 9184106 · DOI
  103. [110]Schulz A. Ajayi T. Specchio N. de Los Reyes E. Gissen P. Ballon D. Dyke J.P. Cahan H. Slasor P. Jacoby D. Study of Intraventricular Cerliponase Alfa for CLN2 Disease N. Engl. J. Med. 2018 378 1898 1907 10.1056/NEJMoa1712649 29688815 · DOI · Paper page
  104. [111]Williams R.E. Adams H.R. Blohm M. Cohen-Pfeffer J.L. de Los Reyes E. Denecke J. Drago K. Fairhurst C. Frazier M. Guelbert N. Management Strategies for CLN2 Disease Pediatr. Neurol. 2017 69 102 112 10.1016/j.pediatrneurol.2017.01.034 28335910 · DOI
  105. [112]Lin L. Lobel P. Production and characterization of recombinant human CLN2 protein for enzyme-replacement therapy in late infantile neuronal ceroid lipofuscinosis Biochem. J. 2001 357 49 55 10.1042/bj3570049 11415435 PMC1221927 · DOI
  106. [113]Meng Y. Sohar I. Wang L. Sleat D.E. Lobel P. Systemic administration of tripeptidyl peptidase I in a mouse model of late infantile neuronal ceroid lipofuscinosis: Effect of glycan modification PLoS ONE 2012 7 e40509 10.1371/journal.pone.0040509 22792360 PMC3391252 · DOI
  107. [114]Vuillemenot B.R. Kennedy D. Reed R.P. Boyd R.B. Butt M.T. Musson D.G. Keve S. Cahayag R. Tsuruda L.S. O’Neill C.A. Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution Toxicol. Appl. Pharmacol. 2014 277 49 57 10.1016/j.taap.2014.03.005 24642058 · DOI
  108. [115]Martin-Kleiner I. Gall Troselj K. Mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) in carcinogenesis Cancer Lett. 2010 289 11 22 10.1016/j.canlet.2009.06.036 19646808 · DOI
  109. [116]Anderson G.W. Goebel H.H. Simonati A. Human pathology in NCL Biochim. Biophys. Acta 2013 1832 1807 1826 10.1016/j.bbadis.2012.11.014 23200925 · DOI
  110. [117]Naseri Kouzehgarani G. Feldsien T. Engelhard H.H. Mirakhur K.K. Phipps C. Nimmrich V. Clausznitzer D. Lefebvre D.R. Harnessing cerebrospinal fluid circulation for drug delivery to brain tissues Adv. Drug Deliv. Rev. 2021 173 20 59 10.1016/j.addr.2021.03.002 33705875 · DOI · Paper page
  111. [118]Mak M. Fung L. Strasser J.F. Saltzman W.M. Distribution of drugs following controlled delivery to the brain interstitium J. Neuro-Oncol. 1995 26 91 102 10.1007/BF01060215 8787851 · DOI
  112. [119]Grossman S.A. Reinhard C. Colvin O.M. Chasin M. Brundrett R. Tamargo R.J. Brem H. The intracerebral distribution of BCNU delivered by surgically implanted biodegradable polymers J. Neurosurg. 1992 76 640 647 10.3171/jns.1992.76.4.0640 1545259 · DOI
  113. [120]Brem H. Piantadosi S. Burger P.C. Walker M. Selker R. Vick N.A. Black K. Sisti M. Brem S. Mohr G. Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group Lancet 1995 345 1008 1012 10.1016/S0140-6736(95)90755-6 7723496 · DOI
  114. [121]Valtonen S. Timonen U. Toivanen P. Kalimo H. Kivipelto L. Heiskanen O. Unsgaard G. Kuurne T. Interstitial chemotherapy with carmustine-loaded polymers for high-grade gliomas: A randomized double-blind study Neurosurgery 1997 41 44 48 discussion 48–49 10.1097/00006123-199707000-00011 9218294 · DOI
  115. [122]Westphal M. Hilt D.C. Bortey E. Delavault P. Olivares R. Warnke P.C. Whittle I.R. Jaaskelainen J. Ram Z. A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma Neuro-Oncology 2003 5 79 88 10.1093/neuonc/5.2.79 12672279 PMC1920672 · DOI
  116. [123]Hart M.G. Grant R. Garside R. Rogers G. Somerville M. Stein K. Chemotherapy wafers for high grade glioma Cochrane Database Syst. Rev. 2011 2011 CD007294 10.1002/14651858.CD007294.pub2 21412902 PMC6457755 · DOI
  117. [124]Bensadoun J.C. Pereira de Almeida L. Fine E.G. Tseng J.L. Deglon N. Aebischer P. Comparative study of GDNF delivery systems for the CNS: Polymer rods, encapsulated cells, and lentiviral vectors J. Control. Release 2003 87 107 115 10.1016/S0168-3659(02)00353-X 12618027 · DOI
  118. [125]Batrakova E.V. Gendelman H.E. Kabanov A.V. Cell-mediated drug delivery Expert Opin. Drug Deliv. 2011 8 415 433 10.1517/17425247.2011.559457 21348773 PMC3062753 · DOI
  119. [126]Bouvier G. Penn R.D. Kroin J.S. Beique R.A. Guerard M.J. Lesage J. Intratumoral chemotherapy with multiple sources Ann. N. Y. Acad. Sci. 1988 531 213 214 10.1111/j.1749-6632.1988.tb31830.x 3289458 · DOI
  120. [127]Yin D. Valles F.E. Fiandaca M.S. Forsayeth J. Larson P. Starr P. Bankiewicz K.S. Striatal volume differences between non-human and human primates J. Neurosci. Methods 2009 176 200 205 10.1016/j.jneumeth.2008.08.027 18809434 PMC2662364 · DOI
  121. [128]Voges J. Reszka R. Gossmann A. Dittmar C. Richter R. Garlip G. Kracht L. Coenen H.H. Sturm V. Wienhard K. Imaging-guided convection-enhanced delivery and gene therapy of glioblastoma Ann. Neurol. 2003 54 479 487 10.1002/ana.10688 14520660 · DOI
  122. [129]Stine C.A. Munson J.M. Convection-Enhanced Delivery: Connection to and Impact of Interstitial Fluid Flow Front. Oncol. 2019 9 966 10.3389/fonc.2019.00966 31632905 PMC6783516 · DOI
  123. [130]Lang A.E. Gill S. Patel N.K. Lozano A. Nutt J.G. Penn R. Brooks D.J. Hotton G. Moro E. Heywood P. Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease Ann. Neurol. 2006 59 459 466 10.1002/ana.20737 16429411 · DOI
  124. [131]Salvatore M.F. Ai Y. Fischer B. Zhang A.M. Grondin R.C. Zhang Z. Gerhardt G.A. Gash D.M. Point source concentration of GDNF may explain failure of phase II clinical trial Exp. Neurol. 2006 202 497 505 10.1016/j.expneurol.2006.07.015 16962582 · DOI
  125. [132]Pardridge W.M. Biopharmaceutical drug targeting to the brain J. Drug Target. 2010 18 157 167 10.3109/10611860903548354 20064077 · DOI
  126. [133]Dunlop D.S. Yang X.R. Lajtha A. The effect of elevated plasma phenylalanine levels on protein synthesis rates in adult rat brain Biochem. J. 1994 302 Pt 2 601 610 10.1042/bj3020601 8093014 PMC1137270 · DOI
  127. [134]Ai Y. Markesbery W. Zhang Z. Grondin R. Elseberry D. Gerhardt G.A. Gash D.M. Intraputamenal infusion of GDNF in aged rhesus monkeys: Distribution and dopaminergic effects J. Comp. Neurol. 2003 461 250 261 10.1002/cne.10689 12724841 · DOI
  128. [135]Eslamboli A. Georgievska B. Ridley R.M. Baker H.F. Muzyczka N. Burger C. Mandel R.J. Annett L. Kirik D. Continuous low-level glial cell line-derived neurotrophic factor delivery using recombinant adeno-associated viral vectors provides neuroprotection and induces behavioral recovery in a primate model of Parkinson’s disease J. Neurosci. 2005 25 769 777 10.1523/JNEUROSCI.4421-04.2005 15673656 PMC6725622 · DOI
  129. [136]Sampson J.H. Archer G. Pedain C. Wembacher-Schroder E. Westphal M. Kunwar S. Vogelbaum M.A. Coan A. Herndon J.E. Raghavan R. Poor drug distribution as a possible explanation for the results of the PRECISE trial J. Neurosurg. 2010 113 301 309 10.3171/2009.11.JNS091052 20020841 · DOI
  130. [137]Mehta A.I. Choi B.D. Raghavan R. Brady M. Friedman A.H. Bigner D.D. Pastan I. Sampson J.H. Imaging of convection enhanced delivery of toxins in humans Toxins 2011 3 201 206 10.3390/toxins3030201 22069706 PMC3202819 · DOI
  131. [138]Lewis G.K. Jr. Schulz Z.R. Pannullo S.C. Southard T.L. Olbricht W.L. Ultrasound-assisted convection-enhanced delivery to the brain in vivo with a novel transducer cannula assembly: Laboratory investigation J. Neurosurg. 2012 117 1128 1140 10.3171/2012.7.JNS11144 22998056 · DOI
  132. [139]Brady M.L. Raghavan R. Mata J. Wilson M. Wilson S. Odland R.M. Broaddus W.C. Large-Volume Infusions into the Brain: A Comparative Study of Catheter Designs Ster. Funct. Neurosurg. 2018 96 135 141 10.1159/000488324 PMC6093288 30021213 · DOI
  133. [140]Vogelbaum M.A. Brewer C. Barnett G.H. Mohammadi A.M. Peereboom D.M. Ahluwalia M.S. Gao S. First-in-human evaluation of the Cleveland Multiport Catheter for convection-enhanced delivery of topotecan in recurrent high-grade glioma: Results of pilot trial 1 J. Neurosurg. 2018 130 476 485 10.3171/2017.10.JNS171845 29652233 · DOI
  134. [141]Faraji A.H. Jaquins-Gerstl A.S. Valenta A.C. Ou Y. Weber S.G. Electrokinetic Convection-Enhanced Delivery of Solutes to the Brain ACS Chem. Neurosci. 2020 11 2085 2093 10.1021/acschemneuro.0c00037 32559365 PMC11059855 · DOI
  135. [142]Valles F. Fiandaca M.S. Bringas J. Dickinson P. LeCouteur R. Higgins R. Berger M. Forsayeth J. Bankiewicz K.S. Anatomic compression caused by high-volume convection-enhanced delivery to the brain Neurosurgery 2009 65 579 585 discussion 576–585 10.1227/01.NEU.0000350229.77462.2F 19687704 PMC2745991 · DOI
  136. [143]Selvaraj K. Gowthamarajan K. Karri V. Nose to brain transport pathways an overview: Potential of nanostructured lipid carriers in nose to brain targeting Artif. Cells Nanomed. Biotechnol. 2018 46 2088 2095 10.1080/21691401.2017.1420073 29282995 · DOI
  137. [145]Quignon P. Giraud M. Rimbault M. Lavigne P. Tacher S. Morin E. Retout E. Valin A.S. Lindblad-Toh K. Nicolas J. The dog and rat olfactory receptor repertoires Genome Biol. 2005 6 R83 10.1186/gb-2005-6-10-r83 16207354 PMC1257466 · DOI
  138. [146]Harkema J.R. Carey S.A. Wagner J.G. The nose revisited: A brief review of the comparative structure, function, and toxicologic pathology of the nasal epithelium Toxicol. Pathol. 2006 34 252 269 10.1080/01926230600713475 16698724 · DOI
  139. [147]Merkus P. Guchelaar H.J. Bosch D.A. Merkus F.W. Direct access of drugs to the human brain after intranasal drug administration? Neurology 2003 60 1669 1671 10.1212/01.WNL.0000067993.60735.77 12771261 · DOI · Paper page
  140. [148]Erdo F. Bors L.A. Farkas D. Bajza A. Gizurarson S. Evaluation of intranasal delivery route of drug administration for brain targeting Brain Res. Bull. 2018 143 155 170 10.1016/j.brainresbull.2018.10.009 30449731 · DOI
  141. [149]Dare A.O. Balos L.L. Grand W. Neural-dural transition at the medial anterior cranial base: An anatomical and histological study with clinical applications J. Neurosurg. 2003 99 362 365 10.3171/jns.2003.99.2.0362 12924711 · DOI
  142. [150]Melin E. Eide P.K. Ringstad G. In vivo assessment of cerebrospinal fluid efflux to nasal mucosa in humans Sci. Rep. 2020 10 14974 10.1038/s41598-020-72031-5 32917953 PMC7486888 · DOI
  143. [151]Faber W.M. The nasal mucosa and the subarachnoid space Am. J. Anat. 1937 62 121 148 10.1002/aja.1000620106 · DOI
  144. [152]Bradbury M.W. Westrop R.J. Factors influencing exit of substances from cerebrospinal fluid into deep cervical lymph of the rabbit J. Physiol. 1983 339 519 534 10.1113/jphysiol.1983.sp014731 6411905 PMC1199176 · DOI
  145. [154]Schuknecht B. Simmen D. Briner H.R. Holzmann D. Nontraumatic skull base defects with spontaneous CSF rhinorrhea and arachnoid herniation: Imaging findings and correlation with endoscopic sinus surgery in 27 patients AJNR Am. J. Neuroradiol. 2008 29 542 549 10.3174/ajnr.A0840 18079185 PMC8118857 · DOI
  146. [155]Sakane T. Akizuki M. Yamashita S. Nadai T. Hashida M. Sezaki H. The transport of a drug to the cerebrospinal fluid directly from the nasal cavity: The relation to the lipophilicity of the drug Chem. Pharm. Bull. 1991 39 2456 2458 10.1248/cpb.39.2456 1804561 · DOI
  147. [156]Van den Berg M.P. Verhoef J.C. Romeijn S.G. Merkus F.W. Uptake of estradiol or progesterone into the CSF following intranasal and intravenous delivery in rats Eur. J. Pharm. Biopharm. 2004 58 131 135 10.1016/j.ejpb.2004.02.010 15207546 · DOI
  148. [157]Van den Berg M.P. Merkus P. Romeijn S.G. Verhoef J.C. Merkus F.W. Uptake of melatonin into the cerebrospinal fluid after nasal and intravenous delivery: Studies in rats and comparison with a human study Pharm. Res. 2004 21 799 802 10.1023/B:PHAM.0000026431.55383.69 15180337 · DOI
  149. [158]Hussain M.A. Rakestraw D. Rowe S. Aungst B.J. Nasal administration of a cognition enhancer provides improved bioavailability but not enhanced brain delivery J. Pharm. Sci. 1990 79 771 772 10.1002/jps.2600790904 2273456 · DOI
  150. [159]Char H. Kumar S. Patel S. Piemontese D. Iqbal K. Malick A.W. Salvador R.A. Behl C.R. Nasal delivery of [14C]dextromethorphan hydrochloride in rats: Levels in plasma and brain J. Pharm. Sci. 1992 81 750 752 10.1002/jps.2600810806 1403718 · DOI
  151. [160]Kaur P. Kim K. Pharmacokinetics and brain uptake of diazepam after intravenous and intranasal administration in rats and rabbits Int. J. Pharm. 2008 364 27 35 10.1016/j.ijpharm.2008.07.030 18760341 · DOI
  152. [161]Wu H. Hu K. Jiang X. From nose to brain: Understanding transport capacity and transport rate of drugs Expert Opin. Drug Deliv. 2008 5 1159 1168 10.1517/17425247.5.10.1159 18817519 · DOI
  153. [162]Sakane T. Yamashita S. Yata N. Sezaki H. Transnasal delivery of 5-fluorouracil to the brain in the rat J. Drug Target. 1999 7 233 240 10.3109/10611869909085506 10680979 · DOI
  154. [163]Dahlin M. Bergman U. Jansson B. Bjork E. Brittebo E. Transfer of dopamine in the olfactory pathway following nasal administration in mice Pharm. Res. 2000 17 737 742 10.1023/A:1007542618378 10955850 · DOI
  155. [164]Bergstrom U. Franzen A. Eriksson C. Lindh C. Brittebo E.B. Drug targeting to the brain: Transfer of picolinic acid along the olfactory pathways J. Drug Target. 2002 10 469 478 10.1080/1061186021000038346 12575737 · DOI
  156. [165]Fukuda M. Kanazawa T. Iioka S. Oguma T. Iwasa R. Masuoka S. Suzuki N. Kosuge Y. Suzuki T. Quantitative analysis of inulin distribution in the brain focused on nose-to-brain route via olfactory epithelium by reverse esophageal cannulation J. Control. Release 2021 332 493 501 10.1016/j.jconrel.2021.02.024 33647429 · DOI
  157. [166]Lopes C. Ribeiro M. Duarte A.I. Humbert S. Saudou F. Pereira de Almeida L. Hayden M. Rego A.C. IGF-1 intranasal administration rescues Huntington’s disease phenotypes in YAC128 mice Mol. Neurobiol. 2014 49 1126 1142 10.1007/s12035-013-8585-5 24347322 · DOI
  158. [167]Barakat N.S. Omar S.A. Ahmed A.A. Carbamazepine uptake into rat brain following intra-olfactory transport J. Pharm. Pharmacol. 2006 58 63 72 10.1211/jpp.58.1.0008 16393465 · DOI
  159. [168]Vaka S.R. Murthy S.N. Enhancement of nose-brain delivery of therapeutic agents for treating neurodegenerative diseases using peppermint oil Pharmazie 2010 65 690 692 21038847 PMC5650656
  160. [169]Gao M. Mei D. Huo Y. Mao S. Effect of polysorbate 80 on the intranasal absorption and brain distribution of tetramethylpyrazine phosphate in rats Drug Deliv. Transl. Res. 2019 9 311 318 10.1007/s13346-018-0580-y 30168052 · DOI
  161. [170]Broadwell R.D. Balin B.J. Salcman M. Transcytotic pathway for blood-borne protein through the blood-brain barrier Proc. Natl. Acad. Sci. USA 1988 85 632 636 10.1073/pnas.85.2.632 2448779 PMC279605 · DOI
  162. [171]Thorne R.G. Emory C.R. Ala T.A. Frey W.H. 2nd Quantitative analysis of the olfactory pathway for drug delivery to the brain Brain Res. 1995 692 278 282 10.1016/0006-8993(95)00637-6 8548316 · DOI · Paper page
  163. [172]Tong W. Dwyer C.A. Thacker B.E. Glass C.A. Brown J.R. Hamill K. Moremen K.W. Sarrazin S. Gordts P. Dozier L.E. Guanidinylated Neomycin Conjugation Enhances Intranasal Enzyme Replacement in the Brain Mol. Ther. 2017 25 2743 2752 10.1016/j.ymthe.2017.08.007 28958576 PMC5768556 · DOI
  164. [173]Luedtke N.W. Carmichael P. Tor Y. Cellular uptake of aminoglycosides, guanidinoglycosides, and poly-arginine J. Am. Chem. Soc. 2003 125 12374 12375 10.1021/ja0360135 14531657 · DOI
  165. [174]Shingaki T. Katayama Y. Nakaoka T. Irie S. Onoe K. Okauchi T. Hayashinaka E. Yamaguchi M. Tanki N. Ose T. Visualization of drug translocation in the nasal cavity and pharmacokinetic analysis on nasal drug absorption using positron emission tomography in the rat Eur. J. Pharm. Biopharm. 2016 99 45 53 10.1016/j.ejpb.2015.11.014 26639201 · DOI
  166. [175]Van de Bittner G.C. Van de Bittner K.C. Wey H.Y. Rowe W. Dharanipragada R. Ying X. Hurst W. Giovanni A. Alving K. Gupta A. Positron Emission Tomography Assessment of the Intranasal Delivery Route for Orexin A ACS Chem. Neurosci. 2018 9 358 368 10.1021/acschemneuro.7b00357 29035509 · DOI
  167. [177]Cacciotti-Saija C. Langdon R. Ward P.B. Hickie I.B. Scott E.M. Naismith S.L. Moore L. Alvares G.A. Redoblado Hodge M.A. Guastella A.J. A double-blind randomized controlled trial of oxytocin nasal spray and social cognition training for young people with early psychosis Schizophr. Bull. 2015 41 483 493 10.1093/schbul/sbu094 24962607 PMC4332939 · DOI · Paper page
  168. [178]Quintana D.S. Westlye L.T. Hope S. Naerland T. Elvsashagen T. Dorum E. Rustan O. Valstad M. Rezvaya L. Lishaugen H. Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: A randomized placebo-controlled double-blind crossover trial Transl. Psychiatry 2017 7 e1136 10.1038/tp.2017.103 28534875 PMC5584522 · DOI · Paper page
  169. [179]Lee M.R. Scheidweiler K.B. Diao X.X. Akhlaghi F. Cummins A. Huestis M.A. Leggio L. Averbeck B.B. Oxytocin by intranasal and intravenous routes reaches the cerebrospinal fluid in rhesus macaques: Determination using a novel oxytocin assay Mol. Psychiatry 2018 23 115 122 10.1038/mp.2017.27 28289281 PMC5862033 · DOI · Paper page
  170. [180]Mayer A.V. Wermter A.K. Stroth S. Alter P. Haberhausen M. Stehr T. Paulus F.M. Krach S. Kamp-Becker I. Randomized clinical trial shows no substantial modulation of empathy-related neural activation by intranasal oxytocin in autism Sci. Rep. 2021 11 15056 10.1038/s41598-021-94407-x 34301983 PMC8302641 · DOI · Paper page
  171. [181]Craft S. Raman R. Chow T.W. Rafii M.S. Sun C.K. Rissman R.A. Donohue M.C. Brewer J.B. Jenkins C. Harless K. Safety, Efficacy, and Feasibility of Intranasal Insulin for the Treatment of Mild Cognitive Impairment and Alzheimer Disease Dementia: A Randomized Clinical Trial JAMA Neurol. 2020 77 1099 1109 10.1001/jamaneurol.2020.1840 32568367 PMC7309571 · DOI · Paper page
  172. [182]Dhuyvetter D. Tekle F. Nazarov M. Vreeken R.J. Borghys H. Rombouts F. Lenaerts I. Bottelbergs A. Direct nose to brain delivery of small molecules: Critical analysis of data from a standardized in vivo screening model in rats Drug Deliv. 2020 27 1597 1607 10.1080/10717544.2020.1837291 33169635 PMC7655051 · DOI
  173. [183]Broman T. Lindberg-Broman A.M. An experimental study of disorders in the permeability of the cerebral vessels (“the Blood-Brain Barrier”) produced by chemical and physico-chemical agents Acta Physiol. Scand. 1945 10 102 125 10.1111/j.1748-1716.1945.tb00297.x · DOI
  174. [184]Rapoport S.I. Effect of concentrated solutions on blood-brain barrier Am. J. Physiol. 1970 219 270 274 10.1152/ajplegacy.1970.219.1.270 5424853 · DOI
  175. [185]Brightman M.W. Hori M. Rapoport S.I. Reese T.S. Westergaard E. Osmotic opening of tight junctions in cerebral endothelium J. Comp. Neurol. 1973 152 317 325 10.1002/cne.901520402 4784295 · DOI
  176. [186]Hasegawa H. Allen J.C. Mehta B.M. Shapiro W.R. Posner J.B. Enhancement of CNS penetration of methotrexate by hyperosmolar intracarotid mannitol or carcinomatous meningitis Neurology 1979 29 1280 1286 10.1212/WNL.29.9_Part_1.1280 573408 · DOI
  177. [187]Barranger J.A. Rapoport S.I. Fredericks W.R. Pentchev P.G. MacDermot K.D. Steusing J.K. Brady R.O. Modification of the blood-brain barrier: Increased concentration and fate of enzymes entering the brain Proc. Natl. Acad. Sci. USA 1979 76 481 485 10.1073/pnas.76.1.481 284363 PMC382965 · DOI
  178. [188]Mayhan W.G. Heistad D.D. Permeability of blood-brain barrier to various sized molecules Am. J. Physiol. 1985 248 H712 H718 10.1152/ajpheart.1985.248.5.H712 2581459 · DOI
  179. [189]Koenig H. Goldstone A.D. Lu C.Y. Polyamines mediate the reversible opening of the blood-brain barrier by the intracarotid infusion of hyperosmolal mannitol Brain Res. 1989 483 110 116 10.1016/0006-8993(89)90040-1 2495841 · DOI
  180. [190]Shapiro W.R. Voorhies R.M. Hiesiger E.M. Sher P.B. Basler G.A. Lipschutz L.E. Pharmacokinetics of tumor cell exposure to [14C]methotrexate after intracarotid administration without and with hyperosmotic opening of the blood-brain and blood-tumor barriers in rat brain tumors: A quantitative autoradiographic study Cancer Res. 1988 48 694 701 3335031
  181. [191]Zunkeler B. Carson R.E. Olson J. Blasberg R.G. DeVroom H. Lutz R.J. Saris S.C. Wright D.C. Kammerer W. Patronas N.J. Quantification and pharmacokinetics of blood-brain barrier disruption in humans J. Neurosurg. 1996 85 1056 1065 10.3171/jns.1996.85.6.1056 8929495 · DOI
  182. [192]Black K.L. Ningaraj N.S. Modulation of brain tumor capillaries for enhanced drug delivery selectively to brain tumor Cancer Control 2004 11 165 173 10.1177/107327480401100304 15153840 · DOI
  183. [193]Neuwelt E.A. Balaban E. Diehl J. Hill S. Frenkel E. Successful treatment of primary central nervous system lymphomas with chemotherapy after osmotic blood-brain barrier opening Neurosurgery 1983 12 662 671 10.1227/00006123-198306000-00013 6410302 · DOI
  184. [194]Pitman S.W. Frei E. 3rd Weekly methotrexate-calcium leucovorin rescue: Effect of alkalinization on nephrotoxicity; pharmacokinetics in the CNS; and use in CNS non-Hodgkin’s lymphoma Cancer Treat. Rep. 1977 61 695 701 18282
  185. [195]Angelov L. Doolittle N.D. Kraemer D.F. Siegal T. Barnett G.H. Peereboom D.M. Stevens G. McGregor J. Jahnke K. Lacy C.A. Blood-brain barrier disruption and intra-arterial methotrexate-based therapy for newly diagnosed primary CNS lymphoma: A multi-institutional experience J. Clin. Oncol. 2009 27 3503 3509 10.1200/JCO.2008.19.3789 19451444 PMC2717756 · DOI
  186. [196]Iorio-Morin C. Gahide G. Morin C. Vanderweyen D. Roy M.A. St-Pierre I. Massicotte-Tisluck K. Fortin D. Management of Primary Central Nervous System Lymphoma Using Intra-Arterial Chemotherapy With Osmotic Blood-Brain Barrier Disruption: Retrospective Analysis of the Sherbrooke Cohort Front. Oncol. 2020 10 543648 10.3389/fonc.2020.543648 33552946 PMC7855856 · DOI
  187. [197]Nadal A. Fuentes E. Pastor J. McNaughton P.A. Plasma albumin is a potent trigger of calcium signals and DNA synthesis in astrocytes Proc. Natl. Acad. Sci. USA 1995 92 1426 1430 10.1073/pnas.92.5.1426 7877995 PMC42532 · DOI
  188. [198]LeVine S.M. Albumin and multiple sclerosis BMC Neurol. 2016 16 47 10.1186/s12883-016-0564-9 27067000 PMC4828783 · DOI · Paper page
  189. [199]Petersen M.A. Ryu J.K. Chang K.J. Etxeberria A. Bardehle S. Mendiola A.S. Kamau-Devers W. Fancy S.P.J. Thor A. Bushong E.A. Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage Neuron 2017 96 1003 1012 10.1016/j.neuron.2017.10.008 29103804 PMC5851281 · DOI
  190. [200]Burks S.R. Kersch C.N. Witko J.A. Pagel M.A. Sundby M. Muldoon L.L. Neuwelt E.A. Frank J.A. Blood-brain barrier opening by intracarotid artery hyperosmolar mannitol induces sterile inflammatory and innate immune responses Proc. Natl. Acad. Sci. USA 2021 118 e2021915118 10.1073/pnas.2021915118 33906946 PMC8106347 · DOI
  191. [201]Kovacs Z.I. Kim S. Jikaria N. Qureshi F. Milo B. Lewis B.K. Bresler M. Burks S.R. Frank J.A. Disrupting the blood-brain barrier by focused ultrasound induces sterile inflammation Proc. Natl. Acad. Sci. USA 2017 114 E75 E84 10.1073/pnas.1614777114 27994152 PMC5224365 · DOI · Paper page
  192. [202]Lossinsky A.S. Vorbrodt A.W. Wisniewski H.M. Scanning and transmission electron microscopic studies of microvascular pathology in the osmotically impaired blood-brain barrier J. Neurocytol. 1995 24 795 806 10.1007/BF01191215 8586999 · DOI
  193. [203]Salahuddin T.S. Johansson B.B. Kalimo H. Olsson Y. Structural changes in the rat brain after carotid infusions of hyperosmolar solutions. An electron microscopic study Acta Neuropathol. 1988 77 5 13 10.1007/BF00688236 3149121 · DOI
  194. [204]Salahuddin T.S. Kalimo H. Johansson B.B. Olsson Y. Observations on exsudation of fibronectin, fibrinogen and albumin in the brain after carotid infusion of hyperosmolar solutions. An immunohistochemical study in the rat indicating longlasting changes in the brain microenvironment and multifocal nerve cell injuries Acta Neuropathol. 1988 76 1 10 10.1007/BF00687674 3293343 · DOI
  195. [205]Elkassabany N.M. Bhatia J. Deogaonkar A. Barnett G.H. Lotto M. Maurtua M. Ebrahim Z. Schubert A. Ference S. Farag E. Perioperative complications of blood brain barrier disruption under general anesthesia: A retrospective review J. Neurosurg. Anesthesiol. 2008 20 45 48 10.1097/ANA.0b013e31815d5f1f 18157025 · DOI
  196. [206]Doolittle N.D. 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. 1998 30 81 90 10.1097/01376517-199804000-00002 9642616 · DOI
  197. [207]Kiviniemi V. Korhonen V. Kortelainen J. Rytky S. Keinanen T. Tuovinen T. Isokangas M. Sonkajarvi E. Siniluoto T. Nikkinen J. Real-time monitoring of human blood-brain barrier disruption PLoS ONE 2017 12 e0174072 10.1371/journal.pone.0174072 28319185 PMC5358768 · DOI
  198. [208]Unterberg A. Wahl M. Baethmann A. Effects of bradykinin on permeability and diameter of pial vessels in vivo J. Cereb. Blood Flow Metab. 1984 4 574 585 10.1038/jcbfm.1984.82 6501443 · DOI
  199. [209]Witherow F.N. Helmy A. Webb D.J. Fox K.A. Newby D.E. Bradykinin contributes to the vasodilator effects of chronic angiotensin-converting enzyme inhibition in patients with heart failure Circulation 2001 104 2177 2181 10.1161/hc4301.098252 11684627 · DOI
  200. [210]Doctrow S.R. Abelleira S.M. Curry L.A. Heller-Harrison R. Kozarich J.W. Malfroy B. McCarroll L.A. Morgan K.G. Morrow A.R. Musso G.F. The bradykinin analog RMP-7 increases intracellular free calcium levels in rat brain microvascular endothelial cells J. Pharmacol. Exp. Ther. 1994 271 229 237 7965719

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Authors
Pardridge, W. M.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Pardridge, William M.
ORCID
Pardridge, William M.
Venue
Pharmaceutics
Publisher
MDPI AG
Published
2022-06-16
Volume
14
Issue
6
Pages
1283
ISSN
1999-4923 (ISSN-L)
DOI
10.3390/pharmaceutics14061283
PMC
PMC9229021
OpenAlex
W4283066304
Cited by
219
References
1,238
Citations by year
2026: 40 · 2025: 60 · 2024: 62 · 2023: 46 · 2022: 11
FWCI
4.60
Type
journal article
Language
en
Open access
Licence
Locations
  • Pharmaceutics (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
brain drug delivery, blood-brain barrier, salvarsan, receptor-mediated transport, blood-brain barrier disruption, lipid carriers, prodrugs, stem cells, exosomes, nanoparticles, gene therapy, biologics

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