El-Sayed Khafagy1,2, Mona F El-Azab3, Mohamed E H ElSayed4,5,6. 1. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University,, Ismailia, 41522, Egypt. 2. College of Engineering, Department of Biomedical Engineering, Cellular Engineering & Nano-Therapeutics Laboratory, University of Michigan, Ann Arbor, Michigan, 48109, USA. 3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University,, Ismailia, 41522, Egypt. 4. College of Engineering, Department of Biomedical Engineering, Cellular Engineering & Nano-Therapeutics Laboratory, University of Michigan, Ann Arbor, Michigan, 48109, USA. melsayed@umich.edu. 5. University of Michigan, Macromolecular Science and Engineering Program, Ann Arbor, Michigan, 48109, USA. melsayed@umich.edu. 6. Department of Biomedical Engineering, University of Michigan, 1101 Beal Avenue, Lurie Biomedical Engineering Building, Room 2150, Ann Arbor, Michigan, 48109, USA. melsayed@umich.edu.
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.
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.
Authors: Raquel F S Gonçalves; Joana T Martins; Luís Abrunhosa; António A Vicente; Ana C Pinheiro Journal: Nanomaterials (Basel) Date: 2021-03-23 Impact factor: 5.076