Resistivity Technique for the Evaluation of the Integrity of Buccal and Esophageal Epithelium Mucosa for In Vitro Permeation Studies: Swine Buccal and Esophageal Mucosa Barrier Models

Abstract

Permeation assays are important for the development of topical formulations applied on buccal mucosa. Swine buccal and esophageal epithelia are usually used as barriers for these assays, while frozen epithelia have been used to optimize the experimental setup. However, there is no consensus on these methods. In transdermal studies, barrier integrity has been evaluated by measuring electrical resistance (ER) across the skin, which has been demonstrated to be a simple, fast, safe, and cost-effective method. Therefore, the aims here were to investigate whether ER might also be an effective method to evaluate buccal and esophageal epithelium mucosa integrity for in vitro permeation studies, and to establish a cut-off ER value for each epithelium mucosa model. We further investigated whether buccal epithelium could be substituted by esophageal epithelium in transbuccal permeation studies, and whether their permeability and integrity were affected by freezing at −20 °C for 3 weeks. Fresh and frozen swine buccal and esophageal epithelia were mounted in Franz diffusion cells and were then submitted to ER measurement. Permeation assays were performed using lidocaine hydrochloride as a hydrophilic drug model. ER was shown to be a reliable method for evaluating esophageal and buccal epithelia. The esophageal epithelium presented higher permeability compared to the buccal epithelium. For both epithelia, freezing and storage led to decreased electrical resistivity and increased permeability. We conclude that ER may be safely used to confirm tissue integrity when it is equal to or above 3 kΩ for fresh esophageal mucosa, but not for buccal epithelium mucosa. However, the use of esophageal epithelium in in vitro transmucosal studies could overestimate the absorption of hydrophilic drugs. In addition, fresh samples are recommended for these experiments, especially when hydrophilic drugs are involved.

Polymeric Micelles Enhance Mucosal Contact Time and Deposition of Fluocinolone Acetonide

“…Porcine esophageal epithelium is commonly used to represent buccal mucosa in in vitro permeation studies due to similarities in histology and permeability with human oral buccal mucosa [ 14 , 39 ]. FA is a hydrophobic drug with low solubility and high permeability, which is attracted to lipids and repelled by water.…”

Buccal Permeation of Polysaccharide High Molecular Weight Compounds: Effect of Chemical Permeation Enhancers

“…The model membrane used for this kind of experiment should be, however, very well characterized. In the literature, there is some evidence indicating that the porcine esophageal mucosa is a relevant model of the buccal epithelium [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. However, most of these studies have been performed with low MW compounds, and these results cannot be directly extrapolated to hydrophilic macromolecules, probably characterized by different penetration pathways [ 37 ].…”

In Vitro Skin Delivery of Griseofulvin by Layer-by-Layer Nanocoated Emulsions Stabilized by Whey Protein and Polysaccharides

“…The reading was determined at 1 kHz with a maximum voltage of 300 mV root-mean-square average in the parallel equivalent circuit mode, using an alternating current [ 46 ]. Only skin samples with an electric resistance higher than 10 kΩ were considered suitable for the studies [ 47 , 48 , 49 ]. The compartments of the Franz-type diffusion cells were emptied, and the acceptor compartments were filled with 2 mL of pH 7.4 phosphate buffer containing 10% methanol for increased solubility of griseofulvin, while the donor compartments were filled with either 1 mL of emulsion, equivalent amounts of dry emulsion, 180 mg, or equivalent amounts of the dry emulsion were redispersed in 1 mL of pure citrate-phosphate buffer pH 5.0.…”