Effect of dodecylmaltoside (DDM) on uptake of BCS III compounds, tiludronate and cromolyn, in Caco-2 cells and rat intestine model

Deshmukh, D. D.; Nagilla, Rakesh; Ravis, William R.; Betageri, Guru V.

doi:10.3109/10717541003604882

Cited by 9 publications

(3 citation statements)

References 28 publications

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“…This difference in recovery may in part be related to the high dose of PS20 (500 µM, 10 times CMC) used, when compared to LM and TL doses at 200 µM (at approximately CMC), or to 200 µM LMG and 1600 µM NG (doses < CMC), see Table 1. Importantly, LM, TL, and LMG led to a rapid decrease in TEER values, NG however did not, followed by a short time epithelial recovery, the former in agreement with previous studies (Deshmukh et al, 2010;Eley and Triumalashetty, 2001). The data suggested that LM, TL and LMG could be well tolerated surfactants for inclusion as absorption enhancers in pharmaceutical formulations.…”

Section: Caco-2 Cell Monolayers Recovered After Multiple Exposures Tosupporting

confidence: 90%

Nonionic surfactants increase digoxin absorption in Caco-2 and MDCKII MDR1 cells: Impact on P-glycoprotein inhibition, barrier function, and repeated cellular exposure

Al-Ali

Steffansen

Holm

et al. 2018

International Journal of Pharmaceutics

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Nonionic surfactants commonly used in pharmaceutical formulations may have P-glycoprotein (P-gp) inhibiting and/or permeation enhancing effects. The present work aims to distinguish these effects and assess the degree of cellular recovery after multiple exposures to nonionic surfactants. The investigated surfactants were polysorbates (PS): PS20, PS40, PS60, PS65, PS80 and PS85; monosaccharide-based: lauroyl methyl glucamide and n-nonyl-β-D-glucopyranoside; or disaccharide-based: lauryl-β-D-maltoside and trehalose 6-laurate. Bi-directional permeability studies of digoxin and mannitol, and calcein-AM efflux assay were performed in cell cultures. Cellular recovery was evaluated by continuous measurements of transepithelial electrical resistance (TEER) in Caco-2 cell monolayers. Polysorbates with one fatty acid chain decreased the efflux of digoxin through P-gp inhibition in MDCKII MDR1 cells. Mono- and di-saccharide-based surfactants, in a dose dependent manner, enhanced digoxin absorptive permeability without decreasing the secretory permeability in Caco-2 cells, suggesting that the surfactants had a transcellular permeation enhancing effect. Caco-2 cell monolayers recovered to different degrees of 60-100% of the initial TEER values. Calcein-AM assay was found to be non-predictive to surfactants influence on digoxin permeability across cell monolayers. In conclusion, these results may assist, in a mechanism-based, selection of suitable surfactants for formulating oral dosage forms to enhance the absorption of low bioavailable P-gp substrates.

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Section: Caco-2 Cell Monolayers Recovered After Multiple Exposures Tosupporting

confidence: 90%

Nonionic surfactants increase digoxin absorption in Caco-2 and MDCKII MDR1 cells: Impact on P-glycoprotein inhibition, barrier function, and repeated cellular exposure

Al-Ali

Steffansen

Holm

et al. 2018

International Journal of Pharmaceutics

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“…This effect was observed in the control group only because of substantial tissue damage and lack of viability in other treatment groups. Damage‐trigger‐induced decrease of PD and TER correlated with an increase in FITC–dextran and LY P app values (Table 3), which are commonly used low‐permeability markers in permeability experiments 81–83. This observation indicates that damage triggers increased leakiness of intestinal epithelia.…”

Section: Resultsmentioning

confidence: 72%

Suitability of Isolated Rat Jejunum Model for Demonstration of Complete Absorption in Humans for BCS-Based Biowaiver Request

Peternel¹,

Kristan²,

Petrushevska³

et al. 2012

Journal of Pharmaceutical Sciences

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“…Even though the use of maltosides as permeation enhancers has been investigated over several years, ,,, a precise mechanism for this effect has yet to be elucidated. Measuring the TEER recovery after exposing tissues/cells to permeation enhancers can, however, give some fundamental understanding about the principal mode of action.…”

Section: Discussionmentioning

confidence: 99%

Interaction with Mixed Micelles in the Intestine Attenuates the Permeation Enhancing Potential of Alkyl-Maltosides

et al. 2015

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The purpose of the present study was to investigate the interaction of intestinal permeation enhancers with lipid and surfactant components present in the milieu of the small intestine. Maltosides of different chain lengths (decyl-, dodecyl-, and tetradecyl-maltoside; DM, DDM, TDM, respectively) were used as examples of nonionic, surfactant-like permeation enhancers, and their effect on the permeation of FD4 across Caco-2 monolayers was monitored. To mimic the environment of the small intestine, modified versions of fasted and fed state simulated intestinal fluid (FaSSIFmod, FeSSIFmod6.5, respectively) were used in addition to standard transport media (TM). Compared to the buffer control, 0.5 mM DDM led to a 200-fold permeation enhancement of FD4 in TM. However, this was dramatically decreased in FaSSIFmod, where a concentration of 5 mM DDM was necessary in order to elicit a moderate, 4-fold, permeation enhancement. Its capacity to promote permeation was diminished further when FeSSIFmod6.5 was employed. Even when cells were exposed to a concentration of 5 mM, no significant permeation enhancement of FD4 was observed. Analogous effects were observed in the case of DM and TDM, with slight deviations on account of differences in their critical micelle concentration (CMC). This observation was corroborated by calculating the amount of maltoside monomer versus micellar bound maltoside in FaSSIFmod and FeSSIFmod6.5, which demonstrated a reduced amount of free monomer in these fluids. To evaluate the in vivo significance of our findings, DDM solutions in TM, FaSSIFmod, and FeSSIFmod6.5 were used for closed intestinal loop studies in rats. Consistent with the results found in in vitro permeation studies, these investigations illustrated the overwhelming impact of sodium taurocholate/lecithin micelles on the permeation enhancing effect of DDM. While DDM led to a 20-fold increase in FD4 bioavailability when it was applied in TM, no significant permeation enhancement was seen in FaSSIFmod/FeSSIFmod6.5. Collectively, these investigations highlight the importance of using biorelevant media when evaluating the potency of permeation enhancers. In doing so, this ensures improved correlations between in vitro and in vivo studies and thus enables an early and more accurate assessment of promising permeation enhancers.

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Effect of dodecylmaltoside (DDM) on uptake of BCS III compounds, tiludronate and cromolyn, in Caco-2 cells and rat intestine model

Cited by 9 publications

References 28 publications

Nonionic surfactants increase digoxin absorption in Caco-2 and MDCKII MDR1 cells: Impact on P-glycoprotein inhibition, barrier function, and repeated cellular exposure

Nonionic surfactants increase digoxin absorption in Caco-2 and MDCKII MDR1 cells: Impact on P-glycoprotein inhibition, barrier function, and repeated cellular exposure

Suitability of Isolated Rat Jejunum Model for Demonstration of Complete Absorption in Humans for BCS-Based Biowaiver Request

Interaction with Mixed Micelles in the Intestine Attenuates the Permeation Enhancing Potential of Alkyl-Maltosides

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