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

Author(s)

Macena de Araujo, Jaiza Samara ^[1] ; Volpato, Maria Cristina ^[1] ; Muniz, Bruno Vilela ^[1] ; Augusto Xavier, Gabriela Gama ^[1] ; Maia Martinelli, Claudia Cristina ^[1] ; Vianna Lopez, Renata Fonseca ^[2] ; Groppo, Francisco Carlos ^[1] ; Franz-Montan, Michelle ^[1]

Affiliation

^[1] Univ Campinas UNICAMP, Piracicaba Dent Sch, Dept Biosci, BR-13414903 Piracicaba, SP - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: PHARMACEUTICS; v. 13, n. 5 MAY 2021.
• Web of Science Citations: 0

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 degrees 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 k omega 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. (AU)

• FAPESP's process: 11/23475-9 - Permeation studies of lidocaine across mucosal oral epithelium
• Grantee: Claudia Cristina Maia Martinelli
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 12/06974-4 - Development, biocompatibility and permeation studies on gel formulations of poly-epsilon-caprolactone nanocapsules containing local anesthetics
• Grantee: Michelle Franz Montan Braga Leite
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 16/14630-4 - Evaluation method to measure integrity of oral mucosa epithelium for permeation studies
• Grantee: Gabriela Gama Xavier Augusto
• Support Opportunities: Scholarships in Brazil - Scientific Initiation