Smuggling drugs into the brain: an overview of ligands targeting transcytosis for drug delivery across the blood–brain barrier.
Open accessAbstract
The blood-brain barrier acts as a physical barrier that prevents free entry of blood-derived substances, including those intended for therapeutic applications. The development of molecular Trojan horses is a promising drug targeting technology that allows for non-invasive delivery of therapeutics into the brain. This concept relies on the application of natural or genetically engineered proteins or small peptides, capable of specifically ferrying a drug-payload that is either directly coupled or encapsulated in an appropriate nanocarrier, across the blood-brain barrier via receptor-mediated transcytosis. Specifically, in this process the nanocarrier-drug system ("Trojan horse complex") is transported transcellularly across the brain endothelium, from the blood to the brain interface, essentially trailed by a native receptor. Naturally, only certain properties would favor a receptor to serve as a transporter for nanocarriers, coated with appropriate ligands. Here we briefly discuss brain microvascular endothelial receptors that have been explored until now, highlighting molecular features that govern the efficiency of nanocarrier-mediated drug delivery into the brain.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Nano-delivery systems of size 100-200 nm can be easily accommodated in transport vesicles for receptor-mediated internalization and vesicular transport.
“Receptor-mediated internalization of cargo followed by vesicular transport is a suitable option as nano-delivery systems of size 100–200 nm range can be easily accommodated in these transport vesicles”
From Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs (2020) · cites this paper as Georgieva et al., 2014
Nanocarriers of size less than 500 Da having the ability to absorb inside cells are suitable for transcellular transportation.
“The nanocarriers of size less than 500 Da having the ability to absorb inside cells are suitable for transcellular transportation”
From Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs (2020) · cites this paper as Georgieva et al., 2014
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Astrocyte-endothelial interactions at the blood-brain barrier
Abbott, N. J., Rönnbäck, L., & Hansson, E. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1824 · Cited by 5,595 · see citing works
Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes
Alvarez-Erviti, L., Seow, Y., Yin, H., Betts, C., Lakhal, S., & Wood, M. J. A. (2011) · Nature Biotechnology · doi:10.1038/nbt.1807 · Cited by 4,930 · see citing works
The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders
Zlokovic, B. V. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.003 · Cited by 3,280 · see citing works
Srimaroeng, C., Cecile, J. P., Walden, R., & Pritchard, J. B. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350077 · Cited by 2,989 · see citing works
Pericytes regulate the blood–brain barrier
Armulik, A., Genové, G., Mäe, M., Nisancioglu, M. H., Wallgard, E., Niaudet, C., He, L., Norlin, J., Lindblom, P., Strittmatter, K., et al. (2010) · Nature · doi:10.1038/nature09522 · Cited by 2,843 · see citing works
In Vivo Protein Transduction: Delivery of a Biologically Active Protein into the Mouse
Schwarze, S. R., Ho, A. L., Vocero-Akbani, A. M., & Dowdy, S. F. (1999) · Science · doi:10.1126/science.285.5433.1569 · Cited by 2,418 · see citing works
The blood–brain barrier: an overview
Ballabh, P., Braun, A., & Nedergaard, M. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2003.12.016 · Cited by 2,276 · see citing works
Caveolin, a protein component of caveolae membrane coats
Rothberg, K. G., Heuser, J. E., Donzell, W. C., Ying, Y., Glenney, J. R., & Anderson, R. G. W. (1992) · Cell · doi:10.1016/0092-8674(92)90143-z · Cited by 2,259 · see citing works
Pericytes are required for blood–brain barrier integrity during embryogenesis
Daneman, R., Zhou, L., Kebede, A. A., & Barres, B. A. (2010) · Nature · doi:10.1038/nature09513 · Cited by 2,128 · see citing works
Anderson, R. G. W. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.199 · Cited by 1,941 · see citing works
Maxfield, F. R., & McGraw, T. E. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1315 · Cited by 1,716 · see citing works
Transvascular delivery of small interfering RNA to the central nervous system
Kumar, P., Wu, H., McBride, J. L., Jung, K.-E., Hee Kim, M., Davidson, B. L., Kyung Lee, S., Shankar, P., & Manjunath, N. (2007) · Nature · doi:10.1038/nature05901 · Cited by 1,246 · see citing works
Mfsd2a is critical for the formation and function of the blood-brain barrier
Ben-Zvi, A., Lacoste, B., Kur, E., Andreone, B. J., Mayshar, Y., Yan, H., & Gu, C. (2014) · Nature · doi:10.1038/nature13324 · Cited by 1,037 · see citing works
Caveolins, Liquid-Ordered Domains, and Signal Transduction
Smart, E. J., Graf, G. A., McNiven, M. A., Sessa, W. C., Engelman, J. A., Scherer, P. E., Okamoto, T., & Lisanti, M. P. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.11.7289 · Cited by 1,005 · see citing works
Schnitzer, J. E., Oh, P., Pinney, E., & Allard, J. F. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.127.5.1217 · Cited by 918 · see citing works
Lindgren, M., Hällbrink, M., Prochiantz, A., & Langel, Ü. (2000) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)01447-4 · Cited by 806 · see citing works
CLATHRIN-COATED VESICLE FORMATION AND PROTEIN SORTING: An Integrated Process
Schmid, S. L. (1997) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.66.1.511 · Cited by 800 · see citing works
Boosting Brain Uptake of a Therapeutic Antibody by Reducing Its Affinity for a Transcytosis Target
Yu, Y. J., Zhang, Y., Kenrick, M., Hoyte, K., Luk, W., Lu, Y., Atwal, J., Elliott, J. M., Prabhu, S., Watts, R. J., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002230 · Cited by 794 · see citing works
Regulated internalization of caveolae.
Parton, R. G., Joggerst, B., & Simons, K. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.127.5.1199 · Cited by 755 · see citing works
Diet-induced obese mice develop peripheral, but not central, resistance to leptin.
van Heek, M., Compton, D. S., France, C. F., Tedesco, R. P., Fawzi, A. B., Graziano, M. P., Sybertz, E. J., Strader, C. D., & Davis, H. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119171 · Cited by 752 · see citing works
Orlandi, P. A., & Fishman, P. H. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.141.4.905 · Cited by 721 · see citing works
EEA1, an Early Endosome-Associated Protein.
Mu, F., Callaghan, J. M., Steele‐Mortimer, O., Stenmark, H., Parton, R. G., Campbell, P. L., McCluskey, J., Yeo, J.-P., Tock, E. P. C., & Toh, B. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.22.13503 · Cited by 714 · see citing works
Bell, R. D., Sagare, A. P., Friedman, A. E., Bedi, G. S., Holtzman, D. M., Deane, R., & Zlokovic, B. V. (2007) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600419 · Cited by 670 · see citing works
Niewoehner, J., Bohrmann, B., Collin, L., Urich, E., Sade, H., Maier, P., Rueger, P., Stracke, J. O., Lau, W., Tissot, A. C., et al. (2014) · Neuron · doi:10.1016/j.neuron.2013.10.061 · Cited by 622 · see citing works
Ulbrich, K., Hekmatara, T., Herbert, E., & Kreuter, J. (2009) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2008.08.021 · Cited by 591 · see citing works
Metalloproteinases: Mediators of Pathology and Regeneration in the CNS
Yong, V. W. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1807 · Cited by 582 · see citing works
Engaging neuroscience to advance translational research in brain barrier biology
Neuwelt, E. A., Bauer, B., Fahlke, C. M., Fricker, G., Iadecola, C., Janigro, D., Leybaert, L., Molnár, Z., O’Donnell, M. E., Povlishock, J. T., et al. (2011) · Nature reviews. Neuroscience · doi:10.1038/nrn2995 · Cited by 577 · see citing works
A New Function for the LDL Receptor: Transcytosis of LDL across the Blood–Brain Barrier
Dehouck, B., Fénart, L., Dehouck, M., Pierce, A., Torpier, G., & Cecchelli, R. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.138.4.877 · Cited by 568 · see citing works
Demeule, M., Currie, J., Bertrand, Y., Ché, C., Nguyen, T., Régina, A., Gabathuler, R., Castaigne, J., & Béliveau, R. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05492.x · Cited by 557 · see citing works
Rapid Cycling of Lipid Raft Markers between the Cell Surface and Golgi Complex
Nichols, B. J., Kenworthy, A. K., Polishchuk, R., Lodge, R., Roberts, T. H., Hirschberg, K., Phair, R. D., & Lippincott‐Schwartz, J. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.153.3.529 · Cited by 525 · see citing works
Significant Transport of Doxorubicin into the Brain with Polysorbate 80-Coated Nanoparticles
Gulyaev, A. E., Gelperina, S. E., Skidan, I. N., Antropov, A. S., Kivman, G. Y., & Kreuter, J. (1999) · Pharmaceutical Research · doi:10.1023/a:1018983904537 · Cited by 521 · see citing works
Bhaskar, S. M. M., Tian, F., Stoeger, T., Kreyling, W. G., de la Fuente, J. M., Grazú, V., Borm, P. J. A., Estrada, G. G., Ntziachristos, V., & Razansky, D. (2010) · Particle and Fibre Toxicology · doi:10.1186/1743-8977-7-3 · Cited by 497 · see citing works
Kounnas, M. Z., Moir, R. D., Rebeck, G. W., Bush, A. I., Argraves, W. S., Tanzi, R. E., Hyman, B. T., & Strickland, D. K. (1995) · Cell · doi:10.1016/0092-8674(95)90320-8 · Cited by 489 · see citing works
Kreuter, J., Ramge, P., Petrov, V. E., Hamm, S., Gelperina, S. E., Engelhardt, B., Alyautdin, R. N., von Briesen, H., & Begley, D. J. (2003) · Pharmaceutical Research · doi:10.1023/a:1022604120952 · Cited by 469 · see citing works
Role of plasmalemmal caveolae in signal transduction
Shaul, P. W., & Anderson, R. G. W. (1998) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1998.275.5.l843 · Cited by 465 · see citing works
Identification and Design of Peptides as a New Drug Delivery System for the Brain
Demeule, M., Régina, A., Ché, C., Poirier, J., Nguyen, T., Gabathuler, R., Castaigne, J., & Béliveau, R. (2007) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.131318 · Cited by 464 · see citing works
Ohtsuki, S., & Terasaki, T. (2007) · Pharmaceutical Research · doi:10.1007/s11095-007-9374-5 · Cited by 456 · see citing works
Zensi, A., Begley, D., Pontikis, C., Legros, C., Mihoreanu, L., Wagner, S., Büchel, C., von Briesen, H., & Kreuter, J. (2009) · Journal of Controlled Release · doi:10.1016/j.jconrel.2009.03.002 · Cited by 438 · see citing works
Cell Penetrating Peptides: Intracellular Pathways and Pharmaceutical Perspectives
Patel, L. N., Zaro, J. L., & Shen, W. (2007) · Pharmaceutical Research · doi:10.1007/s11095-007-9303-7 · Cited by 426 · see citing works
Human Blood—Brain Barrier Insulin Receptor
Pardridge, W. M., Eisenberg, J., & Yang, J. (1985) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1985.tb07167.x · Cited by 399 · see citing works
Receptor-mediated Transcytosis of Lactoferrin through the Blood-Brain Barrier
Fillebeen, C., Descamps, L., Dehouck, M., Fénart, L., Benaı̈ssa, M., Spik, G., Cecchelli, R., & Pierce, A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.11.7011 · Cited by 385 · see citing works
Régina, A., Demeule, M., Ché, C., Lavallée, I., Poirier, J., Gabathuler, R., Béliveau, R., & Castaigne, J. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.260 · Cited by 370 · see citing works
Intracellular Trafficking of Cholesterol Monitored with a Cyclodextrin
Neufeld, E. B., Cooney, A. M., Pitha, J., Dawidowicz, E. A., Dwyer, N. K., Pentchev, P. G., & Blanchette‐Mackie, E. J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.35.21604 · Cited by 358 · see citing works
Pardridge, W. M., Buciak, J. L., & Friden, P. M. (1991) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)20567-5 · Cited by 358 · see citing works
Alyautdin, R. N., Petrov, V. E., Langer, K., Berthold, A., Kharkevich, D. A., & Kreuter, J. (1997) · Pharmaceutical Research · doi:10.1023/a:1012098005098 · Cited by 352 · see citing works
Hori, S., Ohtsuki, S., Hosoya, K., Nakashima, E., & Terasaki, T. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02343.x · Cited by 341 · see citing works
Expression of Leptin Receptor Isoforms in Rat Brain Microvessels
Bjørbæk, C., Elmquist, J. K., Michl, P., Ahima, R. S., Bueren, A. M. V., McCall, A. L., & Flier, J. S. (1998) · Endocrinology · doi:10.1210/endo.139.8.6154 · Cited by 340 · see citing works
TAT-conjugated nanoparticles for the CNS delivery of anti-HIV drugs
Rao, K. S., Reddy, M. K., Horning, J. L., & Labhasetwar, V. D. (2008) · Biomaterials · doi:10.1016/j.biomaterials.2008.08.004 · Cited by 314 · see citing works
Pharmacokinetic Consequences of Pegylation
Hamidi, M., Azadi, A., & Rafiei, P. (2006) · Drug Delivery · doi:10.1080/10717540600814402 · Cited by 303 · see citing works
Göppert, T. M., & Müller, R. H. (2005) · Journal of drug targeting · doi:10.1080/10611860500071292 · Cited by 299 · see citing works
The 4F2hc/LAT1 complex transports l-DOPA across the blood–brain barrier
Kageyama, T., Nakamura, M., Matsuo, A., Yamasaki, Y., Takakura, Y., Hashida, M., Kanai, Y., Naito, M., Tsuruo, T., Minato, N., et al. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02758-x · Cited by 298 · see citing works
Dual control of caveolar membrane traffic by microtubules and the actin cytoskeleton
Mundy, D. I., Machleidt, T., Ying, Y., Anderson, R. G. W., & Bloom, G. S. (2002) · Journal of Cell Science · doi:10.1242/jcs.00117 · Cited by 297 · see citing works
Exploring the caves: cavins, caveolins and caveolae
Hansen, C. G., & Nichols, B. J. (2010) · Trends in Cell Biology · doi:10.1016/j.tcb.2010.01.005 · Cited by 296 · see citing works
WILSON, B., Samanta, M. K., Santhi, K., KUMAR, K., Paramakrishnan, N., & Suresh, B. (2008) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2008.03.009 · Cited by 279 · see citing works
Gaillard, P. J., Appeldoorn, C. C. M., Dorland, R., van Kregten, J., Manca, F., Vugts, D. J., Windhorst, A. D., van Dongen, G. A. M. S., de Vries, H. E., Maussang, D., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0082331 · Cited by 273 · see citing works
Jiang, X., Xin, H., Ren, Q., Gu, J., Zhu, L., Du, F., Feng, C., Xie, Y., Sha, X., & Fang, X. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.09.094 · Cited by 270 · see citing works
PERMEABILITY OF INTESTINAL CAPILLARIES
Simionescu, N., Simionescu, M., & Palade, G. E. (1972) · The Journal of Cell Biology · doi:10.1083/jcb.53.2.365 · Cited by 269 · see citing works
Expression of the neonatal Fc receptor (FcRn) at the blood–brain barrier
Schlachetzki, F., Zhu, C., & Pardridge, W. M. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00840.x · Cited by 268 · see citing works
Preparation and brain delivery property of biodegradable polymersomes conjugated with ox26
Pang, Z., Lu, W., Gao, H., Hu, K., Chen, J., Zhang, C., Gao, X., Jiang, X., & Zhu, C. (2008) · Journal of Controlled Release · doi:10.1016/j.jconrel.2008.03.007 · Cited by 264 · see citing works
Kreuter, J., Hekmatara, T., Dreis, S., Vogel, T., Gelperina, S. E., & Langer, K. (2006) · Journal of Controlled Release · doi:10.1016/j.jconrel.2006.12.012 · Cited by 263 · see citing works
Brain uptake of thiamine-coated nanoparticles
Lockman, P. R., Oyewumi, M. O., Koziara, J. M., Roder, K. E., Mumper, R. J., & Allen, D. D. (2003) · Journal of Controlled Release · doi:10.1016/j.jconrel.2003.08.006 · Cited by 260 · see citing works
Wosik, K., Cayrol, R., Dodelet-Devillers, A., Berthelet, F., Bernard, M., Moumdjian, R. A., Bouthillier, A., Reudelhuber, T. L., & Prat, A. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2088-07.2007 · Cited by 259 · see citing works
Liu, L., Guo, K., Lu, J., Venkatraman, S. S., Luo, D., Ng, K. C., Ling, E., Moochhala, S., & Yang, Y. Y. (2007) · Biomaterials · doi:10.1016/j.biomaterials.2007.11.014 · Cited by 247 · see citing works
Dehouck, B., Dehouck, M., Fruchart, J., & Cecchelli, R. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.126.2.465 · Cited by 234 · see citing works
Tosi, G., Costantino, L., Rivasi, F., Ruozi, B., Leo, E., Vergoni, A. V., Tacchi, R., Bertolini, A., Vandelli, M. A., & Forni, F. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.05.022 · Cited by 233 · see citing works
Alyautdin, R. N., Tezikov, E. B., Ramge, P., Kharkevich, D. A., Begley, D. J., & Kreuter, J. (1998) · Journal of Microencapsulation · doi:10.3109/02652049809006836 · Cited by 229 · see citing works
High transcytosis of melanotransferrin (P97) across the blood–brain barrier
Demeule, M., Poirier, J., Jodoin, J., Bertrand, Y., Desrosiers, R. R., Dagenais, C., Nguyen, T., Lanthier, J., Gabathuler, R., Kennard, M. L., et al. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.01201.x · Cited by 222 · see citing works
Rapid and effective labeling of brain tissue using TAT-conjugated CdS∶Mn/ZnS quantum dots
Santra, S., Yang, H., Stanley, J. T., Holloway, P. H., Moudgil, B. M., Walter, G. A., & Mericle, R. A. (2005) · Chemical Communications · doi:10.1039/b503234b · Cited by 215 · see citing works
Olivier, J.-C., Fenart, L., Chauvet, R., Pariat, C., Cecchelli, R., & Couet, W. (1999) · Pharmaceutical Research · doi:10.1023/a:1018947208597 · Cited by 213 · see citing works
Georgieva, J. V., Kalicharan, D., Couraud, P., Romero, I. A., Weksler, B. B., Hoekstra, D., & Zuhorn, I. S. (2010) · Molecular Therapy · doi:10.1038/mt.2010.236 · Cited by 211 · see citing works
Self-citationMcIntosh, D. P., Tan, X., Oh, P., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.251662398 · Cited by 210 · see citing works
Peptide-derivatized biodegradable nanoparticles able to cross the blood–brain barrier
Costantino, L., Gandolfi, F., Tosi, G., Rivasi, F., Vandelli, M. A., & Forni, F. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.07.013 · Cited by 208 · see citing works
Gupta, Y., Jain, A., & Jain, S. (2007) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp.59.7.0004 · Cited by 193 · see citing works
Tyrosine Phosphorylation of Caveolin-1 in the Endothelium
Aoki, T., Nomura, R., & Fujimoto, T. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4652 · Cited by 192 · see citing works
Comparison of five different targeting ligands to enhance accumulation of liposomes into the brain
van Rooy, I., Mastrobattista, E., Storm, G., Hennink, W. E., & Schiffelers, R. M. (2010) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.11.014 · Cited by 188 · see citing works
The importance of being acid: the role of acidification in intracellular membrane traffic
Mellman, I. (1992) · Journal of Experimental Biology · doi:10.1242/jeb.172.1.39 · Cited by 188 · see citing works
Benchenane, K., Bérézowski, V., Ali, C., Fernández‐Monreal, M., López‐Atalaya, J. P., Brillault, J., Chuquet, J., Nouvelot, A., MacKenzie, E. T., Bu, G., et al. (2005) · Circulation · doi:10.1161/01.cir.0000163542.48611.a2 · Cited by 178 · see citing works
Biopharmaceutical drug targeting to the brain
Pardridge, W. M. (2010) · Journal of drug targeting · doi:10.3109/10611860903548354 · Cited by 172 · see citing works
Maturation models for endosome and lysosome biogenesis
Murphy, R. F. (1991) · Trends in Cell Biology · doi:10.1016/0962-8924(91)90022-2 · Cited by 172 · see citing works
Thorn, H., Stenkula, K. G., Karlsson, M., Ortegren, U., Nystrom, F., Gustavsson, J., & Strålfors, P. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e03-01-0050 · Cited by 170 · see citing works
Moos, T., & Morgan, E. H. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00541.x · Cited by 169 · see citing works
Interaction of Poly(butylcyanoacrylate) Nanoparticles with the Blood-Brain Barrierin vivoandin vitro
Alyaudtin, R. N., Reichel, A., Löbenberg, R., Ramge, P., Kreuter, J., & Begley, D. J. (2001) · Journal of drug targeting · doi:10.3109/10611860108997929 · Cited by 166 · see citing works
Gosk, S., Vermehren, C., Storm, G., & Moos, T. (2004) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/01.wcb.0000135592.28823.47 · Cited by 162 · see citing works
The arguments for pre-existing early and late endosomes
Griffiths, G., & Grüenberg, J. (1991) · Trends in Cell Biology · doi:10.1016/0962-8924(91)90047-d · Cited by 157 · see citing works
Gromnicova, R., Davies, H. A., Sreekanthreddy, P., Romero, I. A., Lund, T., Roitt, I. M., Phillips, J. B., & Male, D. K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081043 · Cited by 157 · see citing works
Efficient transfer of receptor-associated protein (RAP) across the blood-brain barrier
Pan, W., Kastin, A. J., Zankel, T. R., van Kerkhof, P., Terasaki, T., & Bu, G. (2004) · Journal of Cell Science · doi:10.1242/jcs.01381 · Cited by 153 · see citing works
Bearer, E. L., Breakefield, X. O., Schuback, D. E., Reese, T. S., & LaVail, J. H. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.14.8146 · Cited by 150 · see citing works
Rip, J., Chen, L., Hartman, R., van den Heuvel, A., Reijerkerk, A., van Kregten, J., van der Boom, B. G., Appeldoorn, C. C. M., de Boer, M., Maussang, D., et al. (2014) · Journal of drug targeting · doi:10.3109/1061186x.2014.888070 · Cited by 149 · see citing works
Alyautdin, R. N., Gothier, D., Петров, Kharkevich, D. A., & Kreuter, J. (1995) · European Journal of Pharmaceutics and Biopharmaceutics · Cited by 148 · see citing works
Nanoparticles as drug delivery agents specific for CNS: in vivo biodistribution
Vergoni, A. V., Tosi, G., Tacchi, R., Vandelli, M. A., Bertolini, A., & Costantino, L. (2009) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2009.02.005 · Cited by 147 · see citing works
Xie, F., Xie, F., Qin, Yuan, Tang, Zhang, Fan, Chen, Hai, Yao, et al. (2012) · International Journal of Nanomedicine · doi:10.2147/ijn.s23771 · Cited by 142 · see citing works
Choudhury, A., Sharma, D. K., Marks, D. L., & Pagano, R. E. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-05-0432 · Cited by 138 · see citing works
Peptide transport systems for opiates across the blood-brain barrier
Banks, W. A., & Kastin, A. J. (1990) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1990.259.1.e1 · Cited by 138 · see citing works
Candela, P., Gosselet, F., Saint‐Pol, J., Sevin, E., Boucau, M., Boulanger, É., Cecchelli, R., & Fénart, L. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100462 · Cited by 136 · see citing works
Targeted delivery across the blood–brain barrier
Gaillard, P. J., Visser, C. C., & de Boer, A. G. (2005) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2.2.299 · Cited by 130 · see citing works
Endothelial transcytosis in health and disease
Simionescu, M., Popov, D., & Sima, A. V. (2008) · Cell and Tissue Research · doi:10.1007/s00441-008-0688-3 · Cited by 127 · see citing works
Zensi, A., Begley, D. J., Pontikis, C., Legros, C., Mihoreanu, L., Büchel, C., & Kreuter, J. (2010) · Journal of drug targeting · doi:10.3109/1061186x.2010.513712 · Cited by 119 · see citing works
A novel peptide defined through phage display for therapeutic protein and vector neuronal targeting
Liu, J. K., Teng, Q., Garrity‐Moses, M. E., Federici, T., Tănase, D., Imperiale, M. J., & Boulis, N. M. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.01.022 · Cited by 119 · see citing works
Peptide‐Mediated Blood–Brain Barrier Transport of Polymersomes
Georgieva, J. V., Brinkhuis, R. P., Stojanov, K., Weijers, C. A. G. M., Zuilhof, H. T., Rutjes, F. P. J. T., Hoekstra, D., van Hest, J. C. M., & Zuhorn, I. S. (2012) · Angewandte Chemie International Edition · doi:10.1002/anie.201202001 · Cited by 113 · see citing works
Self-citationBoado, R. J., Hui, E. K., Lu, J. Z., Zhou, Q.-H., & Pardridge, W. M. (2010) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2010.01.011 · Cited by 111 · see citing works
Newman, G. R., Campbell, L., von Ruhland, C., Jasani, B., & Gumbleton, M. (1999) · Cell and Tissue Research · doi:10.1007/s004410051217 · Cited by 111 · see citing works
Candela, P., Gosselet, F., Miller, F., Buée‐Scherrer, V., Torpier, G., Cecchelli, R., & Fénart, L. (2008) · Endothelium · doi:10.1080/10623320802487759 · Cited by 111 · see citing works
In vitroandin vivoinvestigation of glucose-mediated brain-targeting liposomes
Qin, Y., Fan, W. Q., Chen, H., Yao, N., Tang, W., Tang, J., Yuan, W., Kuai, R., Zhang, Z., Wu, Y., et al. (2010) · Journal of drug targeting · doi:10.3109/10611861003587235 · Cited by 110 · see citing works
Food, M. R., Rothenberger, S., Gabathuler, R., Haidl, I. D., Reid, G. S. D., & Jefferies, W. A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42043-6 · Cited by 108 · see citing works
Coen, L., Osta, R., Maury, M., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.17.9400 · Cited by 105 · see citing works
A Unique Carrier for Delivery of Therapeutic Compounds beyond the Blood-Brain Barrier
Karkan, D., Pfeifer, C. G., Vitalis, T. Z., Arthur, G., Ujiie, M., Chen, Q., Tsai, S., Koliatis, G., Gabathuler, R., & Jefferies, W. A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002469 · Cited by 103 · see citing works
Tetanus toxin C fragment-conjugated nanoparticles for targeted drug delivery to neurons
Townsend, S. A., Evrony, G. D., Gu, F., Schulz, M. P., Brown, R. H., & Langer, R. (2007) · Biomaterials · doi:10.1016/j.biomaterials.2007.08.011 · Cited by 101 · see citing works
Tosi, G., Fano, R. A., Bondioli, L., Badiali, L., Benassi, R., Rivasi, F., Ruozi, B., Forni, F., & Vandelli, M. A. (2011) · Nanomedicine · doi:10.2217/nnm.11.11 · Cited by 99 · see citing works
Malyukova, I. V., Murray, K. F., Zhu, C., Boedeker, E. C., Kane, A. V., Patterson, K., Peterson, J. R., Donowitz, M., & Kovbasnjuk, O. N. (2008) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.90347.2008 · Cited by 94 · see citing works
Rousselle, C., Clair, P., Smirnova, M., Kolesnikov, Y. A., Pasternak, G. W., Gac-Breton, S., Rees, A. R., Scherrmann, J., & Temsamani, J. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.048520 · Cited by 90 · see citing works
Zloković, B. V., Mačkić, J. B., Djuričić, B., & Davson, H. (1989) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1989.tb08522.x · Cited by 85 · see citing works
Diphtheria toxin receptor-targeted brain drug delivery
Gaillard, P. J., Brink, A., & de Boer, A. G. (2005) · International Congress Series · doi:10.1016/j.ics.2005.02.022 · Cited by 79 · see citing works
Figueiredo, D. M. M., Hallewell, R. A., Chen, L. L., Fairweather, N. F., Gordon Dougan, B., Savitt, J. M., Parks, D. A., & Fishman, P. S. (1997) · Experimental Neurology · doi:10.1006/exnr.1997.6490 · Cited by 78 · see citing works
Ohshima-Hosoyama, S., Simmons, H. A., Goecks, N. C., Joers, V. L., Swanson, C. R., Bondarenko, V., Velotta, R., Brunner, K. G., Wood, L. D., Hruban, R. H., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039036 · Cited by 74 · see citing works
Nano-interventions for neurodegenerative disorders
Fernandes, C., Soni, U., & Patravale, V. B. (2010) · Pharmacological Research · doi:10.1016/j.phrs.2010.02.004 · Cited by 73 · see citing works
Paris‐Robidas, S., Émond, V., Tremblay, C., Soulet, D., & Calon, F. (2011) · Molecular Pharmacology · doi:10.1124/mol.111.071027 · Cited by 69 · see citing works
Boado, R. J., Tsukamoto, H., & Pardridge, W. M. (1998) · Journal of Pharmaceutical Sciences · doi:10.1021/js9800836 · Cited by 68 · see citing works
Sinha, K. A., Box, M., Lalli, G., et al. (2000) · Molecular Microbiology · doi:10.1046/j.1365-2958.2000.02091.x · Cited by 66 · see citing works
Tamaru, M., Akita, H., Fujiwara, T., Kajimoto, K., & Harashima, H. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.03.024 · Cited by 61 · see citing works
Nanoparticulate devices for brain drug delivery
Celia, C., Cosco, D., Paolino, D., & Fresta, M. (2010) · Medicinal Research Reviews · doi:10.1002/med.20201 · Cited by 57 · see citing works
Ragnarsson, E., Schoultz, I., Gullberg, E., Carlsson, A. H., Tafazoli, F., Lerm, M., Magnusson, K., Söderholm, J. D., & Artursson, P. (2008) · Laboratory Investigation · doi:10.1038/labinvest.2008.86 · Cited by 57 · see citing works
Lemke, A., Kiderlen, A. F., Petri, B., & Kayser, O. (2010) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2009.12.004 · Cited by 55 · see citing works
Fishman, P. S., Savitt, J. M., & Farrand, D. A. (1990) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(90)90272-o · Cited by 46 · see citing works
A MEANS FOR TARGETING THERAPEUTICS TO PERIPHERAL NERVOUS SYSTEM NEURONS WITH AXONAL DAMAGE
Federici, T., Liu, J. K., Teng, Q., et al. (2007) · Neurosurgery · doi:10.1227/01.neu.0000255444.44365.b9 · Cited by 45 · see citing works
Caveolae: A Once-Elusive Structure Gets Some Respect
Marx, J. L. (2001) · Science · doi:10.1126/science.294.5548.1862 · Cited by 44 · see citing works
Biousian glycopeptides penetrate the blood–brain barrier
Egleton, R. D., Bilsky, E. J., Tollin, G., et al. (2005) · Tetrahedron Asymmetry · doi:10.1016/j.tetasy.2004.11.038 · Cited by 43 · see citing works
Lück, M., Schröder, W., Harnisch, S., Thode, K., Blunk, T., Paulke, B., Kresse, M., & Müller, R. H. (1997) · Electrophoresis · doi:10.1002/elps.1150181538 · Cited by 39 · see citing works
Gautam, A., Chaudhary, K., Kumar, R., Sharma, A., Kapoor, P., & Tyagi, A. (2016) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/9781681082691116010011 · Cited by 39 · see citing works
Tsuzuki, N., Hama, T., Hibi, T., et al. (1991) · Biochemical Pharmacology · doi:10.1016/0006-2952(91)90616-d · Cited by 38 · see citing works
2B-Trans™ Technology: Targeted Drug Delivery Across the Blood-Brain Barrier
Gaillard, P. J., & de Boer, A. G. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-210-6_8 · Cited by 28 · see citing works
Polt, R. L., & Palian, M. M. (2001) · Drugs of the Future · doi:10.1358/dof.2001.026.06.668342 · Cited by 26 · see citing works
An Engineered Peptide Compound Platform Technology Incorporating Angiopep for Crossing the BBB
Gabathuler, R. (2009) · Neuromethods · doi:10.1007/978-1-60761-529-3_12 · Cited by 6 · see citing works
Evaluation of the cell-penetrating peptide TAT as a trans-blood-brain barrier delivery vehicle
Simon, M. J., Kang, W. H., Gao, S., et al. (2010) · Proceedings of the IEEE Annual Northeast Bioengineering Conference · doi:10.1109/nebc.2010.5458127 · Cited by 4 · see citing works
Lin, N. U., Schwartzberg, L. S., Kesari, S., et al. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.targ-13-b76 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
From blood–brain barrier to blood–brain interface: new opportunities for CNS drug delivery
Banks, W. A. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.21 · Cited by 1,204 · see citing works
Current Strategies for Brain Drug Delivery
Dong, X. (2018) · Theranostics · doi:10.7150/thno.21254 · Cited by 954 · see citing works
“Nanoparticles Actively targeted delivery; brain targeting using specific physiological conditions Crossing the BBB [30-31], [33], [36-39], [44], [46], [47], [50]”
BackgroundNanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs
Naqvi, S., Panghal, A., & Flora, S. J. S. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00494 · Cited by 305 · see citing works
“Three distinct steps are involved in overall transcytosis process: endocytosis of the nanocarrier at the plasma membrane, trafficking of intracellular vesicles toward the opposite surface followed by exocytosis (Rappoport, 2008; Pardridge, 2012; Georgieva et al., 2014).”
BackgroundMedulloblastoma: From Molecular Subgroups to Molecular Targeted Therapies
Wang, J., Garancher, A., Ramaswamy, V., & Wechsler-Reya, R. J. (2018) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-070815-013838 · Cited by 113 · see citing works
Ligand conjugation: An emerging platform for enhanced brain drug delivery
Nabi, B., Rehman, S., Khan, S., Baboota, S., & Ali, J. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2018.08.003 · Cited by 44 · see citing works
Short Peptide-Mediated Brain-Targeted Drug Delivery with Enhanced Immunocompatibility
Guan, J., Jiang, Z., Wang, M., Liu, Y., Liu, J., Yang, Y., Ding, T., Lu, W., Gao, C., Qian, J., et al. (2019) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.8b01216 · Cited by 34 · see citing works
Tomak, A., Saglam-Metiner, P., Coban, R., Oksel-Karakus, C., & Yesil-Celiktas, O. (2025) · Tissue and Cell · doi:10.1016/j.tice.2025.103080 · Cited by 6 · see citing works
- Authors
- Georgieva, J., Hoekstra, D., & Zuhorn, I.
- Affiliations
- University Medical Center Groningen (NL)
- Corresponding author
- Zuhorn, Inge
- Venue
- Pharmaceutics
- Publisher
- MDPI AG
- Published
- 2014-11-17
- Volume
- 6
- Issue
- 4
- Pages
- 557-583
- ISSN
- 1999-4923 (ISSN-L)
- PMC
- PMC4279133
- OpenAlex
- W2150581897
- Cited by
- 211
- References
- 134
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 10 · 2023: 10 · 2022: 21 · 2021: 23 · 2020: 23 · 2019: 18 · 2018: 24 · 2017: 19 · 2016: 19 · 2015: 10 · 2014: 1
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Pharmaceutics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- Top Institute Pharma
- 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
- blood-brain barrier, transcytosis, receptor-mediated transcytosis, Trojan horse, brain drug delivery, nanocarriers, ligands, peptide ligands, receptor engineering, brain endothelium
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
