Dataset Information

Probing the Action of Permeation Enhancers Sodium Cholate and N-dodecyl-?-D-maltoside in a Porcine Jejunal Mucosal Explant System.

ABSTRACT: The small intestinal epithelium constitutes a major permeability barrier for the oral administration of therapeutic drugs with poor bioavailability, and permeation enhancers (PEs) are required to increase the paracellular and/or transcellular uptake of such drugs. Many PEs act as surfactants by perturbing cell membrane integrity and causing permeabilization by leakage or endocytosis. The aim of the present work was to study the action of sodium cholate (NaC) and N-dodecyl-?-D-maltoside (DDM), using a small intestinal mucosal explant system. At 2 mM, both NaC and DDM caused leakage into the enterocyte cytosol of the fluorescent probe Lucifer Yellow, but they also blocked the constitutive endocytotic pathway from the brush border. In addition, an increased paracellular passage of 3-kDa Texas Red Dextran into the lamina propria was observed. By electron microscopy, both PEs disrupted the hexagonal organization of microvilli of the brush border and led to the apical extrusion of vesicle-like and amorphous cell debris to the lumen. In conclusion, NaC and DDM acted in a multimodal way to increase the permeability of the jejunal epithelium both by paracellular and transcellular mechanisms. However, endocytosis, commonly thought to be an uptake mechanism that may be stimulated by PEs, was not involved in the transcellular process.

SUBMITTER: Danielsen EM

PROVIDER: S-EPMC6320951 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Probing the Action of Permeation Enhancers Sodium Cholate and N-dodecyl-β-D-maltoside in a Porcine Jejunal Mucosal Explant System.

Danielsen E Michael EM Hansen Gert H GH

Pharmaceutics 20181002 4

The small intestinal epithelium constitutes a major permeability barrier for the oral administration of therapeutic drugs with poor bioavailability, and permeation enhancers (PEs) are required to increase the paracellular and/or transcellular uptake of such drugs. Many PEs act as surfactants by perturbing cell membrane integrity and causing permeabilization by leakage or endocytosis. The aim of the present work was to study the action of sodium cholate (NaC) and N-dodecyl-β-D-maltoside (DDM), us ...[more]

PMID: 30279382

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Project description:Introduction:Carrier-free autologous mucosal epithelial cell sheets have been clinically utilized as a cell therapy for various epithelial disorders. Fabrication of a transplantable oral mucosal epithelial cell sheet without mouse feeder layers requires a higher seeding density than that of a sheet with mouse feeder layer culture; therefore, a large amount of donor mucosal tissue is needed. However, cell grafts co-cultured with mouse feeder layers are classified by the US Food and Drug Administration (FDA) as xenogeneic products. The goal of this study was to evaluate the utility of oral mucosal epithelial cells expanded by primary explant culture for the fabrication of an adequate number of transplantable epithelial cell sheets without mouse feeder layers. Methods:Small fragments derived from minced oral mucosal tissue were placed into culture dishes for primary explant culture in keratinocyte culture medium. After primary explant culture, the outgrown cells were treated with trypsin-EDTA and were seeded on a temperature-responsive cell culture insert. After subculture, the cultured cells were harvested as a confluent cell sheet from the culture vessel by temperature reduction. Results:Carrier-free human oral mucosal epithelial cell sheets were fabricated in all human cases, and autologous transplantation of the harvested cell sheets showed rapid epithelial regeneration to cover epithelial defects in a rabbit model. The explant culture method, involving the use of small fragments for primary culture, was sufficient for preparing a large number of mucosal epithelial cells without mouse feeder layers. Moreover, oral mucosal epithelial cells derived from the primary explant culture after cryopreservation allowed for the fabrication of cell sheets. Conclusions:This method for fabricating transplantable oral mucosal epithelial cell sheets is an attractive technique for regenerative medicine. It offers a patient-friendly manufacturing method in which a small amount of biopsy material from the patient represents a sufficient epithelial cell source, and a manufacturing plan for preparing cell grafts can be easily tailored.

Dataset Information

Probing the Action of Permeation Enhancers Sodium Cholate and N-dodecyl-?-D-maltoside in a Porcine Jejunal Mucosal Explant System.

Publications

Probing the Action of Permeation Enhancers Sodium Cholate and N-dodecyl-β-D-maltoside in a Porcine Jejunal Mucosal Explant System.

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