Tight junction modulation and its relationship to drug delivery

SALAMA, N; EDDINGTON, N; FASANO, A

doi:10.1016/j.addr.2006.01.003

Cited by 357Barrier Structure and Function StudiesDrug Transport and Resistance MechanismsDrug Solubulity and Delivery Systems

Tight junction modulation and its relationship to drug delivery

SALAMA, N, EDDINGTON, N, FASANO, A·2006·Advanced Drug Delivery Reviews

DOI 10.1016/j.addr.2006.01.003

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Abstract

In order for therapeutic agents to exert their pharmacological effects, they have to cross the biological membranes into the systemic circulation and reach the site of action. Drugs cross the membranes by one of two pathways; paracellular or transcellular. Most drugs are transported transcellularly depending on their physiocochemical properties, however the paracellular route is usually the main route of absorption for hydrophilic drugs (proteins, peptides, etc.). The paracellular pathway is governed by the tight junctions (TJs). The modulation of the TJs by absorption enhancers for paracellular drug transport enhancement and hence drug delivery improvement has been hampered for so many years by lack of comprehensive understanding of the structure and function of the TJs. The TJs are a multiple unit structure composed of multiprotein complex that affiliates with the underlying apical actomyosin ring. TJ proteins identified include transmembrane proteins; occludin and claudin, and cytoplasmic plaque proteins; ZO-1, ZO-2, ZO-3, cingulin, and 7H6. Among the new absorption enhancers that evolved in the past few years is Zonula Occludens toxin, Zot. In vivo and in vitro studies have shown that Zot and its biologically active fragment DeltaG could be effectively used to increase the transport/absorption of paracellular markers and low bioavailable drugs across the intestinal epithelium. Above all, the transient opening of the TJs by Zot suggests that it could be used as a novel approach for the safe drug delivery of therapeutic agents.

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Preservation of the intestinal barrier's integrity relies on the tight junctions between intestinal epithelial cells and their molecular structure including ZO and occludin.
“The preservation of the intestinal barrier’s integrity relies on the tight junctions between intestinal epithelial cells and their molecular structure including the cytoplasmic and transmembrane proteins, ZO, and occludin [63].”
From Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson’s Disease (2023) · cites this paper as [63]

The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors
Ridley, A. J., & Hall, A. (1992) · Cell · doi:10.1016/0092-8674(92)90163-7 · Cited by 4,469 · see citing works
Identification of ZO-1: a high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia.
Stevenson, B. R., Siliciano, J. D., Mooseker, M. S., & Goodenough, D. A. (1986) · The Journal of Cell Biology · doi:10.1083/jcb.103.3.755 · Cited by 1,640 · see citing works
Direct association of occludin with ZO-1 and its possible involvement in the localization of occludin at tight junctions.
Furuse, M., Itoh, M., Hirase, T., Nagafuchi, A., Yonemura, S., Tsukita, S., & Tsukita, S. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.127.6.1617 · Cited by 965 · see citing works
Tight junctions and the molecular basis for regulation of paracellular permeability
Anderson, J. M., & Itallie, C. M. V. (1995) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1995.269.4.g467 · Cited by 844 · see citing works
Route of Passive Ion Permeation in Epithelia
FRÖMTER, E., & Diamond, J. M. (1972) · Nature New Biology · doi:10.1038/newbio235009a0 · Cited by 771 · see citing works
MOLECULAR ARCHITECTURE OF TIGHT JUNCTIONS
Mitic, L. L., & Anderson, J. M. (1998) · Annual Review of Physiology · doi:10.1146/annurev.physiol.60.1.121 · Cited by 721 · see citing works
ZO-3, a Novel Member of the MAGUK Protein Family Found at the Tight Junction, Interacts with ZO-1 and Occludin
Haskins, J., Gu, L., Wittchen, E. S., Hibbard, J. G., & Stevenson, B. R. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.141.1.199 · Cited by 599 · see citing works
Occludin and claudins in tight-junction strands: leading or supporting players?
Tsukita, S., & Furuse, M. (1999) · Trends in Cell Biology · doi:10.1016/s0962-8924(99)01578-0 · Cited by 597 · see citing works
Vibrio cholerae produces a second enterotoxin, which affects intestinal tight junctions.
Fasano, A., Baudry, B., Pumplin, D. W., Wasserman, S. S., Tall, B. D., Ketley, J. M., & Kaper, J. B. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.12.5242 · Cited by 579 · see citing works
Self-citation
The 220-kD protein colocalizing with cadherins in non-epithelial cells is identical to ZO-1, a tight junction-associated protein in epithelial cells: cDNA cloning and immunoelectron microscopy.
Itoh, M., Nagafuchi, A., Yonemura, S., Kitani-Yasuda, T., Tsukita, S., & Tsukita, S. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.121.3.491 · Cited by 576 · see citing works
A Synthetic Peptide Corresponding to the Extracellular Domain of Occludin Perturbs the Tight Junction Permeability Barrier
Wong, V., & Gumbiner, B. M. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.136.2.399 · Cited by 540 · see citing works
Identification of a 160-kDa polypeptide that binds to the tight junction protein ZO-1.
Gumbiner, B., Lowenkopf, T., & Apatira, D. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.8.3460 · Cited by 523 · see citing works
REGULATION OF THE MOVEMENT OF SOLUTES ACROSS TIGHT JUNCTIONS
Madara, J. (1998) · Annual Review of Physiology · doi:10.1146/annurev.physiol.60.1.143 · Cited by 522 · see citing works
Cingulin, a new peripheral component of tight junctions
Citi, S., Sabanay, H., Jakes, R., Geiger, B., & Kendrick‐Jones, J. (1988) · Nature · doi:10.1038/333272a0 · Cited by 515 · see citing works
Enteric bacterial toxins: mechanisms of action and linkage to intestinal secretion
Sears, C. L., & Kaper, J. B. (1996) · Microbiological Reviews · doi:10.1128/mr.60.1.167-215.1996 · Cited by 506 · see citing works
IV. Regulation of tight junctions by extracellular stimuli: nutrients, cytokines, and immune cells
Nusrat, A., Turner, J. R., & Madara, J. (2000) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.2000.279.5.g851 · Cited by 499 · see citing works
Signaling through focal adhesion kinase
Hanks, S. K., & Polte, T. R. (1997) · BioEssays · doi:10.1002/bies.950190208 · Cited by 472 · see citing works
Human zonulin, a potential modulator of intestinal tight junctions
Wang, W., Uzzau, S., Goldblum, S. E., & Fasano, A. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.24.4435 · Cited by 470 · see citing works
Self-citation
Molecular characterization and tissue distribution of ZO-2, a tight junction protein homologous to ZO-1 and the Drosophila discs-large tumor suppressor protein
Jesaitis, L. A., & Goodenough, D. A. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.124.6.949 · Cited by 458 · see citing works
Rho protein regulates tight junctions and perijunctional actin organization in polarized epithelia.
Nusrat, A., Giry, M., Turner, J. R., Colgan, S. P., Parkos, C. A., Carnes, D. K., Lemichez, E., Boquet, P., & Madara, J. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.23.10629 · Cited by 418 · see citing works
Molecular structure and assembly of the tight junction
Denker, B. M., & Nigám, S. K. (1998) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.1998.274.1.f1 · Cited by 405 · see citing works
Characterization of ZO-1, a protein component of the tight junction from mouse liver and Madin-Darby canine kidney cells.
Anderson, J. M., Stevenson, B. R., Jesaitis, L. A., Goodenough, D. A., & Mooseker, M. S. (1988) · The Journal of Cell Biology · doi:10.1083/jcb.106.4.1141 · Cited by 368 · see citing works
The junction-associated protein, zonula occludens-1, localizes to the nucleus before the maturation and during the remodeling of cell-cell contacts.
Gottardi, C. J., Arpin, M., Fanning, A. S., & Louvard, D. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.20.10779 · Cited by 367 · see citing works
SYSTEMIC AND PULMONARY HAEMODYNAMIC EFFECTS OF SOMATOSTATIN
Hallemans, R., Naeije, R., Mélot, C., Mols, P., & Reding, R. (1981) · The Lancet · doi:10.1016/s0140-6736(81)92444-2 · Cited by 352 · see citing works
Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization, in vitro.
Fasano, A., Fiorentini, C., Donelli, G., Uzzau, S., Kaper, J. B., Margaretten, K., Ding, X., Guandalini, S., Comstock, L. E., & Goldblum, S. E. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118114 · Cited by 342 · see citing works
Self-citation
Intestinal absorptive cell tight junctions are linked to cytoskeleton
Madara, J. (1987) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1987.253.1.c171 · Cited by 342 · see citing works
Absorption Enhancement through Intracellular Regulation of Tight Junction Permeability by Medium Chain Fatty Acids in Caco-2 Cells
Lindmark, T., Kimura, Y., & Artursson, P. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37216-7 · Cited by 333 · see citing works
(C) Means to enhance penetration
Swenson, E. S., & Curatolo, W. J. (1992) · Advanced Drug Delivery Reviews · doi:10.1016/0169-409x(92)90015-i · Cited by 314 · see citing works
Symplekin, a novel type of tight junction plaque protein.
Keon, B. H., Schäfer, S. C., Kuhn, C., Gründ, C., & Franke, W. W. (1996) · The Journal of Cell Biology · doi:10.1083/jcb.134.4.1003 · Cited by 285 · see citing works
Nasal absorption of insulin: enhancement by hydrophobic bile salts.
Gordon, G. S., Moses, A. C., Silver, R. D., et al. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.21.7419 · Cited by 278 · see citing works
Protein kinase inhibitors prevent junction dissociation induced by low extracellular calcium in MDCK epithelial cells
Citi, S. (1992) · The Journal of Cell Biology · doi:10.1083/jcb.117.1.169 · Cited by 277 · see citing works
LYSOSOMES IN DIVIDING CELLS.
Rb, G., Anderson, GRAY, K. G., et al. (1965) · PubMed · Cited by 276 · see citing works
Crohn's disease--a permeability disorder of the tight junction?
Hollander, D. (1988) · Gut · doi:10.1136/gut.29.12.1621 · Cited by 271 · see citing works
A PERSISTENT DEFECT IN INTESTINAL PERMEABILITY IN COELIAC DISEASE DEMONSTRATED BY A 51Cr-LABELLED EDTA ABSORPTION TEST
Bjarnason, I., Peters, T. B., & Veall, N. (1983) · The Lancet · doi:10.1016/s0140-6736(83)91628-8 · Cited by 268 · see citing works
Modulation of intestinal tight junctions by Zonula occludens toxin permits enteral administration of insulin and other macromolecules in an animal model.
Fasano, A., & Uzzau, S. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119271 · Cited by 267 · see citing works
Self-citation
Monoclonal antibody 7H6 reacts with a novel tight junction-associated protein distinct from ZO-1, cingulin and ZO-2.
Zhong, Y., Saitoh, T., Minase, T., Sawada, N., Enomoto, K., & Mori, M. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.120.2.477 · Cited by 266 · see citing works
The Intestinal Permeability Barrier: A Hypothesis as to Its Regulation and Involvement in Crohn's Disease
Hollander, D. (1992) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365529209011172 · Cited by 265 · see citing works
THE TIGHT JUNCTION: Morphology to Molecules
Stevenson, B. R., & Keon, B. H. (1998) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.14.1.89 · Cited by 256 · see citing works
Cell signalling: MAGUK magic
Anderson, J. M. (1996) · Current Biology · doi:10.1016/s0960-9822(02)00501-8 · Cited by 251 · see citing works
Intestinal Permeability Enhancement: Efficacy, Acute Local Toxicity, and Reversibility
Swenson, E. S., Milisen, W. B., & Curatolo, W. J. (1994) · Pharmaceutical Research · doi:10.1023/a:1018984731584 · Cited by 251 · see citing works
A small rab GTPase is distributed in cytoplasmic vesicles in non polarized cells but colocalizes with the tight junction marker ZO-1 in polarized epithelial cells
Zahraoui, A., Joberty, G., Arpin, M., Fontaine, J., Hellio, R., Tavitian, A., & Louvard, D. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.124.1.101 · Cited by 228 · see citing works
IMMUNE COMPLEXES CONTAINING FOOD PROTEINS IN NORMAL AND ATOPIC SUBJECTS AFTER ORAL CHALLENGE AND EFFECT OF SODIUM CROMOGLYCATE ON ANTIGEN ABSORPTION
Paganelli, R., Levinsky, R. J., Brostoff, J., et al. (1979) · The Lancet · doi:10.1016/s0140-6736(79)92230-x · Cited by 225 · see citing works
Sodium Caprate Elicits Dilatations in Human Intestinal Tight Junctions and Enhances Drug Absorption by the Paracellular Route
Anderberg, E. K., Lindmark, T., & Artursson, P. (1993) · Pharmaceutical Research · doi:10.1023/a:1018909210879 · Cited by 221 · see citing works
Paracellular Diffusion in Caco-2 Cell Monolayers: Effect of Perturbation on the Transport of Hydrophilic Compounds That Vary in Charge and Size
Knipp, G. T., Ho, N. F. H., Barsuhn, C. L., & Borchardt, R. T. (1997) · Journal of Pharmaceutical Sciences · doi:10.1021/js9700309 · Cited by 208 · see citing works
Zonula Occludens Toxin Structure-Function Analysis
Pierro, M. D., Lu, R., Uzzau, S., Wang, W., Margaretten, K., Pazzani, C., Maimone, F., & Fasano, A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009674200 · Cited by 206 · see citing works
Self-citation
Biogenesis of tight junctions: The c-terminal domain of occludin mediates basolateral targeting
Matter, K., & Balda, M. S. (1998) · Journal of Cell Science · doi:10.1242/jcs.111.4.511 · Cited by 189 · see citing works
Cloning of a gene (zot) encoding a new toxin produced by Vibrio cholerae
Baudry, B., Fasano, A., Ketley, J., & Kaper, J. B. (1992) · Infection and Immunity · doi:10.1128/iai.60.2.428-434.1992 · Cited by 188 · see citing works
Self-citation
Mechanisms of absorption enhancement and tight junction regulation
Hochman, J. H., & Artursson, P. (1994) · Journal of Controlled Release · doi:10.1016/0168-3659(94)90072-8 · Cited by 186 · see citing works
Applications of the Caco-2 model in the design and development of orally active drugs: elucidation of biochemical and physical barriers posed by the intestinal epithelium
Gan, L.-S. L., & Thakker, D. R. (1997) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(96)00427-9 · Cited by 176 · see citing works
The epithelial tight junction: Structure, function and preliminary biochemical characterization
Stevenson, B. R., Anderson, J. M., & BULLIVANT, S. (1988) · Molecular and Cellular Biochemistry · doi:10.1007/bf00226141 · Cited by 176 · see citing works
The enterotoxic effect of zonula occludens toxin on rabbit small intestine involves the paracellular pathway
Fasano, A., Uzzau, S., Fiore, C., & Margaretten, K. (1997) · Gastroenterology · doi:10.1053/gast.1997.v112.pm9041245 · Cited by 172 · see citing works
Self-citation
Absorption-Enhancing Mechanism of EDTA, Caprate, and Decanoylcarnitine in Caco-2 Cells
Tomita, M., Hayashi, M., & Awazu, S. (1996) · Journal of Pharmaceutical Sciences · doi:10.1021/js9504604 · Cited by 169 · see citing works
One hundred years of journal publication
Appel, T. A. (1998) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1998.274.1.c1 · Cited by 164 · see citing works
Flux Measurements across Caco-2 Monolayers May Predict Transport in Human Large Intestinal Tissue
Rubas, W., Cromwell, M. E. M., Shahrokh, Z., Villagran, J., Nguyen, T. N. Q., Wellton, M., Nguyen, T.-H., & Mrsny, R. J. (1996) · Journal of Pharmaceutical Sciences · doi:10.1021/js950267+ · Cited by 160 · see citing works
N-Trimethylated Chitosan Chloride (TMC) Improves the Intestinal Permeation of the Peptide Drug Buserelin In Vitro (Caco-2 Cells) and In Vivo (Rats)
Thanou, M., Florea, B. I., Langemeÿer, M. W. E., et al. (2000) · Pharmaceutical Research · doi:10.1023/a:1007558206506 · Cited by 145 · see citing works
Involvement of a Heterotrimeric G Protein α Subunit in Tight Junction Biogenesis
Denker, B. M., Saha, C., Khawaja, S., & Nigám, S. K. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.42.25750 · Cited by 134 · see citing works
Expression of the catalytic domain of myosin light chain kinase increases paracellular permeability
Hecht, G. A., Pestic, L., Nikčević, G., Koutsouris, A., Tripuraneni, J., Lorimer, D. D., Nowak, G., Guerriero, V., Elson, E. L., & de Lanerolle, P. (1996) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1996.271.5.c1678 · Cited by 133 · see citing works
Identification of Isoforms of G Proteins and PKC that Colocalize with Tight Junctions
Dodane, V., & Kachar, B. (1996) · The Journal of Membrane Biology · doi:10.1007/s002329900020 · Cited by 125 · see citing works
Differential solubilization of proteins, phospholipids, and cholesterol of erythrocyte membranes by detergents
Kirkpatrick, F. H., Gordesky, S. E., & Marinetti, G. V. (1974) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(74)90254-5 · Cited by 111 · see citing works
Absorption-enhancing mechanism of sodium caprate and decanoylcarnitine in Caco-2 cells.
Tomita, M., Hayashi, M., & AWAZU, S. (1995) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)24472-x · Cited by 102 · see citing works
Chemical Stability of Nucleic Acid–Derived Drugs
Pogocki, D., & Schöneich, C. (2000) · Journal of Pharmaceutical Sciences · doi:10.1002/(sici)1520-6017(200004)89:4 · Cited by 100 · see citing works
Dodecylphosphocholine-mediated enhancement of paracellular permeability and cytotoxicity in Caco-2 cell monolayers
Liu, D.-Z., LeCluyse, E. L., & Thakker, D. R. (1999) · Journal of Pharmaceutical Sciences · doi:10.1021/js990094e · Cited by 96 · see citing works
Cytotoxicity of Absorption Enhancers in Caco-2 Cell Monolayers
Sakai, M., Imai, T., Ohtake, H., et al. (1998) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.1998.tb03319.x · Cited by 87 · see citing works
Absorption Enhancement in Intestinal Epithelial Caco-2 Monolayers by Sodium Caprate: Assessment of Molecular Weight Dependence and Demonstration of Transport Routes
Lindmark, T., Schipper, N. G. M., Lazorova, L., et al. (1998) · Journal of drug targeting · doi:10.3109/10611869808995876 · Cited by 84 · see citing works
Intestinal zonulin: open sesame!
Fasano, A. (2001) · Gut · doi:10.1136/gut.49.2.159 · Cited by 80 · see citing works
Self-citation
Extracellular ATP, intracellular calcium and canalicular contraction in rat hepatocyte doublets
Kitamura, T., Brauneis, U., Gatmaitan, Z., & Arias, I. M. (1991) · Hepatology · doi:10.1002/hep.1840140411 · Cited by 78 · see citing works
Zonula Occludens Toxin Increases the Permeability of Molecular Weight Markers and Chemotherapeutic Agents Across the Bovine Brain Microvessel Endothelial Cells
Karyekar, C. S., Fasano, A., Raje, S. V., et al. (2003) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.10310 · Cited by 77 · see citing works
Self-citation
Toxins and the gut: role in human disease
Fasano, A. (2002) · Gut · doi:10.1136/gut.50.suppl_3.iii9 · Cited by 74 · see citing works
Self-citation
The Molecular Weight Dependence of Nasal Absorption: The Effect of Absorption Enhancers
Donovan, M. D., Flynn, G. L., & Amidon, G. L. (1990) · Pharmaceutical Research · doi:10.1023/a:1015904730599 · Cited by 71 · see citing works
In vitro and in vivo analysis of the mechanism of absorption enhancement by palmitoylcarnitine.
Hochman, J. H., Fix, J. A., & LeCluyse, E. L. (1994) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)38767-7 · Cited by 70 · see citing works
Expression of Vibrio cholerae zonula occludens toxin and analysis of its subcellular localization
Uzzau, S., Cappuccinelli, P., & Fasano, A. (1999) · Microbial Pathogenesis · doi:10.1006/mpat.1999.0312 · Cited by 68 · see citing works
Self-citation
Affinity Purification and Partial Characterization of the Zonulin/Zonula Occludens Toxin (Zot) Receptor from Human Brain
Lu, R., Wang, W., Uzzau, S., Vigorito, R. D., Zielke, H. R., & Fasano, A. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0740320.x · Cited by 67 · see citing works
Self-citation
Absorption Enhancement, Structural Changes in Tight Junctions and Cytotoxicity Caused by Palmitoyl Carnitine in Caco-2 and IEC-18 Cells
Duizer, E., Wulp, C. V. D., Versantvoort, C. H. M., et al. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37802-4 · Cited by 66 · see citing works
Cross-talk between enteric pathogens and the intestine
Uzzau, S., & Fasano, A. (2000) · Cellular Microbiology · doi:10.1046/j.1462-5822.2000.00041.x · Cited by 60 · see citing works
Self-citation
Characterization of XerC‐ and XerD‐dependent CTX phage integration in Vibrio cholerae
McLeod, S. M., & Waldor, M. K. (2004) · Molecular Microbiology · doi:10.1111/j.1365-2958.2004.04309.x · Cited by 60 · see citing works
Enhanced Permeability of Molecular Weight Markers and Poorly Bioavailable Compounds Across Caco-2 Cell Monolayers Using the Absorption Enhancer, Zonula Occludens Toxin
Cox, D. S., Raje, S. V., Gao, H., et al. (2002) · Pharmaceutical Research · doi:10.1023/a:1020709513562 · Cited by 58 · see citing works
Absorption-Enhancing Effects of Sodium Caprate and Palmitoyl Carnitine in Rat and Human Colons
Shimazaki, T., Tomita, M., Sadahiro, S., et al. (1998) · Digestive Diseases and Sciences · doi:10.1023/a:1018835829643 · Cited by 56 · see citing works
Zonula Occludens Toxin Is a Powerful Mucosal Adjuvant for Intranasally Delivered Antigens
Marinaro, M., Tommaso, A. D., Uzzau, S., et al. (1999) · Infection and Immunity · doi:10.1128/iai.67.3.1287-1291.1999 · Cited by 56 · see citing works
In vitro models for selection of development candidates. Permeability studies to define mechanisms of absorption enhancement
LeCluyse, E. L., & Sutton, S. C. (1997) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(96)00434-6 · Cited by 53 · see citing works
Enhancing the permeation of marker compounds and enaminone anticonvulsants across Caco-2 monolayers by modulating tight junctions using zonula occludens toxin
Cox, D. S. (2001) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/s0939-6411(01)00172-2 · Cited by 50 · see citing works
Effect of anionic surfactants, nonionic surfactants and neutral salts on the conformation of spin-labeled erythrocyte membrane proteins
Kirkpatrick, F. H., & Howard, E. S. (1973) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(73)90351-9 · Cited by 49 · see citing works
Purification and preliminary characterization of the zonula occludens toxin receptor from human (CaCo2) and murine (IEC6) intestinal cell lines
Uzzau, S., Lu, R., Wang, W., Fiore, C., & Fasano, A. (2001) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2001.tb09437.x · Cited by 46 · see citing works
Self-citation
The Impact of ΔG on the Oral Bioavailability of Low Bioavailable Therapeutic Agents
Salama, N. N., Fasano, A., Thakar, M., et al. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.073205 · Cited by 45 · see citing works
Self-citation
Topical Effects of Absorption Enhancing Agents on the Rectal Mucosa of Rats in Vivo
van Hoogdalem, E. J., Vermeij-Kerrs, C., de Boer, A. G., et al. (1990) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600791004 · Cited by 40 · see citing works
Cellular microbiology: can we learn cell physiology from microorganisms?
Fasano, A. (1999) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1999.276.4.c765 · Cited by 40 · see citing works
Self-citation
Affinity purification of the hepatic high-density lipoprotein receptor identifies two acidic glycoproteins and enables further characterization of their binding properties
Hidaka, H., & Fidge, N. (1992) · Biochemical Journal · doi:10.1042/bj2840161 · Cited by 40 · see citing works
Effect of the biologically active fragment of zonula occludens toxin, ΔG, on the intestinal paracellular transport and oral absorption of mannitol
Salama, N. N., Fasano, A., Lu, R., et al. (2003) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(02)00589-6 · Cited by 39 · see citing works
Self-citation
Intranasal toxicity of selected absorption enhancers.
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Zonula occludens toxin (Zot) interferes with the induction of nasal tolerance to gliadin
Rossi, M., Maurano, F., Luongo, D., et al. (2002) · Immunology Letters · doi:10.1016/s0165-2478(02)00038-x · Cited by 9 · see citing works
Tight junctions: facts and models.
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Authors: SALAMA, N., EDDINGTON, N., & FASANO, A.
Affiliations: University of Maryland, Baltimore (US)
Corresponding author: FASANO, A
ORCID: SALAMA, N
Venue: Advanced Drug Delivery Reviews
Publisher: Elsevier BV
Published: 2006-04-20
Volume: 58
Issue: 1
Pages: 15-28
ISSN: 0169-409X (ISSN-L)
DOI: 10.1016/j.addr.2006.01.003
OpenAlex: W2153192347
Cited by: 357
References: 95
Citations by year: 2026: 10 · 2025: 14 · 2024: 10 · 2023: 17 · 2022: 14 · 2021: 15 · 2020: 20 · 2019: 13 · 2018: 17 · 2017: 17 · 2016: 17 · 2015: 17 · 2014: 27 · 2013: 26 · 2012: 22
FWCI: 12.93
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Advanced Drug Delivery Reviews (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
Keywords: tight junctions, absorption enhancers, zonula occludens toxin, zot, intestinal epithelium, occludin, claudins, ZO-1, ZO-2, ZO-3, cingulin, tight junction modulation, drug delivery
MeSH terms: Animals, Cholera Toxin, Pharmaceutical Preparations, Endotoxins, Humans, Intestinal Absorption, Drug Delivery Systems, Tight Junctions

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Tight junction modulation and its relationship to drug delivery

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