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
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...
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| Format: | Article |
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MDPI AG
2021-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/5/643 |
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| author | Jaiza Samara Macena de Araújo Maria Cristina Volpato Bruno Vilela Muniz Gabriela Gama Augusto Xavier Claudia Cristina Maia Martinelli Renata Fonseca Vianna Lopez Francisco Carlos Groppo Michelle Franz-Montan |
| author_facet | Jaiza Samara Macena de Araújo Maria Cristina Volpato Bruno Vilela Muniz Gabriela Gama Augusto Xavier Claudia Cristina Maia Martinelli Renata Fonseca Vianna Lopez Francisco Carlos Groppo Michelle Franz-Montan |
| author_sort | Jaiza Samara Macena de Araújo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T11:45:55Z |
| format | Article |
| id | doaj.art-17507a140ed341cdaadff638974d526d |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T11:45:55Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-17507a140ed341cdaadff638974d526d2023-11-21T18:03:45ZengMDPI AGPharmaceutics1999-49232021-04-0113564310.3390/pharmaceutics13050643Resistivity Technique for the Evaluation of the Integrity of Buccal and Esophageal Epithelium Mucosa for In Vitro Permeation Studies: Swine Buccal and Esophageal Mucosa Barrier ModelsJaiza Samara Macena de Araújo0Maria Cristina Volpato1Bruno Vilela Muniz2Gabriela Gama Augusto Xavier3Claudia Cristina Maia Martinelli4Renata Fonseca Vianna Lopez5Francisco Carlos Groppo6Michelle Franz-Montan7 Department of Biosciences, Piracicaba Dental School, University of Campinas-UNICAMP, Piracicaba 13414-903, São Paulo, Brazil Department of Biosciences, Piracicaba Dental School, University of Campinas-UNICAMP, Piracicaba 13414-903, São Paulo, Brazil Department of Biosciences, Piracicaba Dental School, University of Campinas-UNICAMP, Piracicaba 13414-903, São Paulo, Brazil Department of Biosciences, Piracicaba Dental School, University of Campinas-UNICAMP, Piracicaba 13414-903, São Paulo, Brazil Department of Biosciences, Piracicaba Dental School, University of Campinas-UNICAMP, Piracicaba 13414-903, São Paulo, Brazil School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo-USP, Ribeirão Preto 14040-903, São Paulo, Brazil Department of Biosciences, Piracicaba Dental School, University of Campinas-UNICAMP, Piracicaba 13414-903, São Paulo, Brazil Department of Biosciences, Piracicaba Dental School, University of Campinas-UNICAMP, Piracicaba 13414-903, São Paulo, BrazilPermeation 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.https://www.mdpi.com/1999-4923/13/5/643membrane resistivityesophageal epitheliumbuccal epitheliummucosal drug deliveryin vitro modelstransbuccal drug delivery |
| spellingShingle | Jaiza Samara Macena de Araújo Maria Cristina Volpato Bruno Vilela Muniz Gabriela Gama Augusto Xavier Claudia Cristina Maia Martinelli Renata Fonseca Vianna Lopez Francisco Carlos Groppo Michelle Franz-Montan 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 Pharmaceutics membrane resistivity esophageal epithelium buccal epithelium mucosal drug delivery in vitro models transbuccal drug delivery |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | membrane resistivity esophageal epithelium buccal epithelium mucosal drug delivery in vitro models transbuccal drug delivery |
| url | https://www.mdpi.com/1999-4923/13/5/643 |
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