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Rhamnolipids Enhance in Vivo Oral Bioavailability of Poorly Absorbed Molecules

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Abstract

Purpose

This report describes the effect of rhamnolipids (RLs) on the tight junctions (TJ) of the intestinal epithelium using the rat in-situ closed loop model.

Methods

We investigated the transport of 5 (6)-carboxyfluorescein (CF) and fluorescein isothiocyanate-labeled dextrans with average molecular weights of 4.4 and 10 kDa (FD-4 and FD-10) when co-administered with different concentrations of RLs. Lactate dehydrogenase (LDH) leakage assay and histopathological examination of treated intestinal loops were used to assess potential toxicity of RLs. Further, the effect of kaempferol on accelerating the resealing of the tight junctions in vivo was also investigated

Results

Data shows that administration of different RLs concentrations (1.0–5.0% v/v) increased CF absorption through rat intestine by 2.84- and 15.82-folds with RLs concentrations of 1.0% and 5.0% v/v, respectively. RLs exhibited size-dependent increase on FD-4 and FD-10 absorption. Dosing RLs at 1.0% v/v didn’t cause a significant LDH leakage or histopathological changes to intestinal mucosa compared to higher concentrations, which showed a progressive damaging effect. Using kaempferol, a natural flavonoid that stimulates the assembly of the TJs, proved to enhance the recovery of barrier properties of the intestinal mucosa treated with high concentrations of RLs (2.5% and 5% v/v).

Conclusions

These results collectively illustrate the ability of RLs to enhance oral bioavailability of different molecules across the intestinal epithelial membrane in a concentration- and time-dependent fashion.

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Abbreviations

AUC:

The total area under the curve

CF:

5(6)-carboxyfluorescein

Cmax:

The peak plasma concentration

ER:

Enhancement ratio

FD-4:

Fluorescein isothiocyanate-labeled dextrans with average molecular weights of 4.4 kDa

FD-10:

Fluorescein isothiocyanate-labeled dextrans with average molecular weights of 10 kDa

H&E:

Hematoxylin and eosin

i.p:

Intraperitoneal

JAM:

Junctional adhesion molecules

LDH:

Lactate dehydrogenase

PBS:

Phosphate-buffered saline

RLs:

Rhamnolipids

TJs:

Tight junctions

Tmax:

Time required to reach Cmax (Tmax)

ZO:

Zonula occludens

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Authors and Affiliations

  1. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University,, Ismailia, 41522, Egypt

    El-Sayed Khafagy

  2. College of Engineering, Department of Biomedical Engineering, Cellular Engineering & Nano-Therapeutics Laboratory, University of Michigan, Ann Arbor, Michigan, 48109, USA

    El-Sayed Khafagy & Mohamed E. H. ElSayed

  3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University,, Ismailia, 41522, Egypt

    Mona F. El-Azab

  4. University of Michigan, Macromolecular Science and Engineering Program, Ann Arbor, Michigan, 48109, USA

    Mohamed E. H. ElSayed

  5. Department of Biomedical Engineering, University of Michigan, 1101 Beal Avenue, Lurie Biomedical Engineering Building, Room 2150, Ann Arbor, Michigan, 48109, USA

    Mohamed E. H. ElSayed

Authors
  1. El-Sayed Khafagy
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  2. Mona F. El-Azab
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Correspondence to Mohamed E. H. ElSayed.

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Khafagy, ES., El-Azab, M.F. & ElSayed, M.E.H. Rhamnolipids Enhance in Vivo Oral Bioavailability of Poorly Absorbed Molecules. Pharm Res 34, 2197–2210 (2017). https://doi.org/10.1007/s11095-017-2227-y

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