Physiological mechanism for enhancement of paracellular drug transport

Hayashi, Masahiro; Sakai, Toyohiko; Hasegawa, Yoshinori; Nishikawahara, T; Tomioka, Haruyo; Iida, Aiko; Shimizu, Nobuo; Tomita, Mikio; Awazu, Shoji

doi:10.1016/s0168-3659(99)00031-0

Cited by 71 publications

(41 citation statements)

References 10 publications

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“…According to the results, it was considered that one of the action mechanisms of acylcarnitines and organic acids is that the intracellular acidosis increases the calcium level through the decrease in ATP levels, opening the tight junction, which is followed by enhanced transport through the paracellular pathway. Thus, CA appears to be a safe and potent enhancer (21,28). In addition the IND permeation from E-O/W containing CA (1.510 ± 0.067mg) was significantly higher than that obtained from IND-Sol (0.191 ± 0.140).…”

Section: Ex Vivo Permeation Studiesmentioning

confidence: 84%

Permeation Studies of Indomethacin from Different Emulsions for Nasal Delivery and Their Possible Anti-Inflammatory Effects

et al. 2008

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Abstract. The purpose of this research was to develop an emulsion formulation of indomethacin (IND) suitable for nasal delivery. IND was incorporated into the oil phases of oil in water (O/W) and water in oil (W/O) emulsions. For this purpose, different emulsifying agents (Tween 80, Span 80 and Brij 58) were used in two emulsion formulations. When the effects of several synthetic membranes (nylon, cellulose, cellulose nitrate) were compared with the sheep nasal mucosa, the cellulose membrane and sheep nasal mucosa showed similar permeation properties for O/W emulsion (P > 0.05). To examine the absorption characteristics of IND, the anti-inflammatory properties of intravenous solution of IND, intranasal O/W emulsions of IND (with or without enhancers) and intranasal solution of IND (IND-Sol) were investigated in rats with carrageenan-induced paw edema. When citric acid was added to the nasal emulsion, the anti-inflammatory activity was similar to that of intravenous solution (P > 0.05). Finally, it was concluded that, intranasal administration of IND emulsion with citric acid may be considered as an alternative to intravenous and per oral administrations of IND to overcome their adverse effects.

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Section: Ex Vivo Permeation Studiesmentioning

confidence: 84%

Permeation Studies of Indomethacin from Different Emulsions for Nasal Delivery and Their Possible Anti-Inflammatory Effects

et al. 2008

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“…19,20,[22][23][24][25] It was reported that bile salt such as taurocholic acid enhanced permeability by removing epithelial cells, which constitute a major permeability barrier. 26,27) For bile salts, the rank order of the promoting effect was sodium deoxycholateϾsodium glycocholateϾsodium taurocholate.…”

Section: Resultsmentioning

confidence: 99%

Electrophysiological Characterization of Tight Junctional Pathway of Rabbit Cornea Treated with Ophthalmic Ingredients

Nakamura

Yamada

Teshima

et al. 2007

Biological & Pharmaceutical Bulletin

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“…Shepard et al reported that endothelial cell shrinkage might be an important mechanism that is related to endothelial macromolecule permeability (19). It was also found that opening of the tight junctions is dependent on increased [Ca 2+ ] i through interaction with phospholipase C in the membrane and that this process enhances permeability in rodent colonic epithelial cells (7). It is possible that decrease in cell size might be related to increases in the intercellular space.…”

Section: Discussionmentioning

confidence: 99%

“…] i through interaction with phospholipase C in the membrane and that this process enhances permeability in rodent colonic epithelial cells (7). In bovine pulmonary artery endothelial cells, activation of store-operated Ca 2+ entry is associated with intercellular gap formation and increased barrier transport of macromolecules (8).…”

Section: +mentioning

confidence: 99%

P2Y Receptor-Mediated Ca2+ Signaling Increases Human Vascular Endothelial Cell Permeability

et al. 2004

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Abstract. We investigated the effects of P2-receptor agonists on cell size, intracellular calcium levels ( ] i by 2meS-ATP were blocked by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, P2Y 1 -antagonist), thapsigargin (Ca 2+-pump inhibitor), and U73122 (phospholipase C inhibitor). Furthermore, 2meS-ATP (P2Y 1 -receptor agonist) enhanced permeation of FD-4 through the endothelial cell monolayer. The 2meS-ATP-induced enhancement of the permeation was also prevented by PPADS, thapsigargin, and U73122. These results indicate that activation of P2Y receptors induces a decrease in cell size, an increase in [Ca 2+ ] i , and may participate in facilitating macromolecular permeability in HUVEC.

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Physiological mechanism for enhancement of paracellular drug transport

Cited by 71 publications

References 10 publications

Permeation Studies of Indomethacin from Different Emulsions for Nasal Delivery and Their Possible Anti-Inflammatory Effects

Permeation Studies of Indomethacin from Different Emulsions for Nasal Delivery and Their Possible Anti-Inflammatory Effects

Electrophysiological Characterization of Tight Junctional Pathway of Rabbit Cornea Treated with Ophthalmic Ingredients

P2Y Receptor-Mediated Ca2+ Signaling Increases Human Vascular Endothelial Cell Permeability

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