Dodecylmaltoside Modulates Bicellular Tight Junction Contacts To Promote Enhanced Permeability
Intestinal permeation enhancers are a crucial component of many oral formulations, without which many drugs would show an insufficient absorption in the gut. The present study sought to provide a better understanding of the molecular interaction of such absorption enhancers with the intestine, by investigating the effect of the surfactant-like permeation enhancer dodecylmaltoside (DDM) on Caco-2 cells. The extent to which the action of DDM is apportioned between the para- and transcellular routes was addressed by examining the transport of relevant marker compounds ([3H]-mannitol and [3H]-propranolol, respectively). In the case of [3H]-mannitol, a robust permeation enhancement was achieved with 0.5 mM DDM (∼6-fold), whereas little effect was seen on the permeation of [3H]-propranolol. Concomitantly measured TEER values revealed a rapid onset of action of DDM with a swift recovery and complete restitution (>90%) within 4 h after washout. To localize the site(s) of action of DDM at the absorptive surface of Caco-2 cells, sulfo-NHS-SS-biotin, a membrane-impermeable compound, was applied apically. In the presence of 0.5 mM DDM, translocated biotin was found to be accumulated toward bicellular contacts, whereas no biotin permeation was observed in untreated control cells. Western blot analysis of DDM-treated and untreated Caco-2 cells revealed an interaction of DDM with specific tight junction associated proteins, resulting in a reduction of claudin-3 and -4 and also occludin, as well as a depletion of claudin-2 from lipid rafts. Collectively, the results presented provide a more in depth understanding of the molecular mechanism(s) underlying the permeation-enhancing actions of DDM.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2017 |
|---|---|
| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
|---|---|
| Enthalten in: |
Molecular pharmaceutics - 14(2017), 12 vom: 04. Dez., Seite 4734-4740 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Gradauer, K [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
3OWL53L36A |
|---|
| Anmerkungen: |
Date Completed 27.07.2018 Date Revised 25.10.2018 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1021/acs.molpharmaceut.7b00297 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM276543939 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM276543939 | ||
| 003 | DE-627 | ||
| 005 | 20231225012241.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2017 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1021/acs.molpharmaceut.7b00297 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0921.xml |
| 035 | |a (DE-627)NLM276543939 | ||
| 035 | |a (NLM)28985076 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Gradauer, K |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Dodecylmaltoside Modulates Bicellular Tight Junction Contacts To Promote Enhanced Permeability |
| 264 | 1 | |c 2017 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 27.07.2018 | ||
| 500 | |a Date Revised 25.10.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Intestinal permeation enhancers are a crucial component of many oral formulations, without which many drugs would show an insufficient absorption in the gut. The present study sought to provide a better understanding of the molecular interaction of such absorption enhancers with the intestine, by investigating the effect of the surfactant-like permeation enhancer dodecylmaltoside (DDM) on Caco-2 cells. The extent to which the action of DDM is apportioned between the para- and transcellular routes was addressed by examining the transport of relevant marker compounds ([3H]-mannitol and [3H]-propranolol, respectively). In the case of [3H]-mannitol, a robust permeation enhancement was achieved with 0.5 mM DDM (∼6-fold), whereas little effect was seen on the permeation of [3H]-propranolol. Concomitantly measured TEER values revealed a rapid onset of action of DDM with a swift recovery and complete restitution (>90%) within 4 h after washout. To localize the site(s) of action of DDM at the absorptive surface of Caco-2 cells, sulfo-NHS-SS-biotin, a membrane-impermeable compound, was applied apically. In the presence of 0.5 mM DDM, translocated biotin was found to be accumulated toward bicellular contacts, whereas no biotin permeation was observed in untreated control cells. Western blot analysis of DDM-treated and untreated Caco-2 cells revealed an interaction of DDM with specific tight junction associated proteins, resulting in a reduction of claudin-3 and -4 and also occludin, as well as a depletion of claudin-2 from lipid rafts. Collectively, the results presented provide a more in depth understanding of the molecular mechanism(s) underlying the permeation-enhancing actions of DDM | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a claudins | |
| 650 | 4 | |a lipid rafts | |
| 650 | 4 | |a maltoside | |
| 650 | 4 | |a permeation enhancement | |
| 650 | 4 | |a tight junctions | |
| 650 | 7 | |a Detergents |2 NLM | |
| 650 | 7 | |a Glucosides |2 NLM | |
| 650 | 7 | |a Mannitol |2 NLM | |
| 650 | 7 | |a 3OWL53L36A |2 NLM | |
| 650 | 7 | |a dodecyl maltoside |2 NLM | |
| 650 | 7 | |a 69227-93-6 |2 NLM | |
| 650 | 7 | |a Propranolol |2 NLM | |
| 650 | 7 | |a 9Y8NXQ24VQ |2 NLM | |
| 700 | 1 | |a Iida, M |e verfasserin |4 aut | |
| 700 | 1 | |a Watari, A |e verfasserin |4 aut | |
| 700 | 1 | |a Kataoka, M |e verfasserin |4 aut | |
| 700 | 1 | |a Yamashita, S |e verfasserin |4 aut | |
| 700 | 1 | |a Kondoh, M |e verfasserin |4 aut | |
| 700 | 1 | |a Buckley, S T |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Molecular pharmaceutics |d 2004 |g 14(2017), 12 vom: 04. Dez., Seite 4734-4740 |w (DE-627)NLM154556807 |x 1543-8392 |7 nnns |
| 773 | 1 | 8 | |g volume:14 |g year:2017 |g number:12 |g day:04 |g month:12 |g pages:4734-4740 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1021/acs.molpharmaceut.7b00297 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 14 |j 2017 |e 12 |b 04 |c 12 |h 4734-4740 | ||