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A method for evaluating drug penetration and absorption through isolated buccal mucosa with highly accuracy and reproducibility

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Abstract

The purpose of the project is to establish a standardized operation method of the in vitro permeability model to maximize mucosal integrity and viability. The model drug lidocaine permeability, 20 kDa fluorescein isothiocyanate-dextran, H&E staining, and mucosal viability were used as evaluation indicators. Firstly, the buccal mucosae of rats, rabbits, dogs, porcine, and humans were analyzed by H&E staining and morphometric analysis to compare the differences. Then, we studied a series of operation methods of isolated mucosa. The buccal mucosae were found to retain their integrity in Kreb’s bicarbonate ringer solution at 4 °C for 36 h. Under the long-term storage method with program cooling, freezing at −80 °C, thawing at 37 °C, and using cryoprotectants of 20% glycerol and 20% trehalose, mucosal integrity and biological viability can be maintained for 21 days. The heat separation method was used to prepare a permeability model with a mucosal thickness of 500 μm, which was considered to be the optimal operation. In summary, this study provided an experimental basis for the selection and operation of in vitro penetration models, standardized the research process of isolated mucosa, and improved the accuracy of permeability studies.

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Availability of data and materials

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Yanji Guangming Meat Factory and Yanji Dongxing Slaughterhouse for providing animal mucosae.

Funding

This work was supported by National Natural Science Foundation of China (82073778), Higher Education Discipline Innovation Project (111 Project D18012), and Natural Science Foundation of Yanbian University. (602020043).

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Authors and Affiliations

  1. Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China

    Shuangqing Wang, Lei Liu, Saige Meng, Zhonggao Gao, Along Zuo & Jianpeng Guo

  2. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China

    Shuangqing Wang & Zhonggao Gao

  3. Yanbian University Hospital, Yanji, 133002, Jilin Province, China

    Yuling Wang

  4. Department of Stomatology, Shengli Oilfield Central Hospital, Dongying, 257000, Shandong Province, China

    Daofeng Liu

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  1. Shuangqing Wang
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  2. Lei Liu
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Contributions

Conceptualization, Jianpeng Guo, Along Zuo, and Zhonggao Gao. Methodology, Shuangqing Wang. Validation, Shuangqing Wang and Lei Liu. Formal analysis, Shuangqing Wang, Saige Meng, Yuling Wang, and Daofeng Liu. Investigation, Lei Liu, Saige Meng, Yuling Wang, and Daofeng Liu. Resources, Jianpeng Guo, Along Zuo, and Zhonggao Gao. Data curation, Shuangqing Wang. Writing–original draft preparation–Shuangqing Wang and Saige Meng. Writing–review and editing–Jianpeng Guo, Along Zuo, and Zhonggao Gao. Visualization, Shuangqing Wang. Supervision, Jianpeng Guo, Along Zuo, and Zhonggao Gao. Project administration, Jianpeng Guo. Funding acquisition, Zhonggao Gao and Along Zuo. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Zhonggao Gao, Along Zuo or Jianpeng Guo.

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Ethics approval and consent to participate

All experiments were carried out in accordance with the Institutional Animal Care and Use Committee of Yanbian University Hospital. Informed consent was obtained from all individual participants included in the study.

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The authors affirm that human research participants provided informed consent for publication of the images in Fig. 1A.

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The authors declare no competing interests.

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Highlights

• Histological analysis of common buccal mucosa

• Glycerol and trehalose – an excellent combination of cryoprotectants

• Evaluation methods of mucosal integrity and biological viability

• The standardized operation of the in vitro permeability model

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Wang, S., Liu, L., Meng, S. et al. A method for evaluating drug penetration and absorption through isolated buccal mucosa with highly accuracy and reproducibility. Drug Deliv. and Transl. Res. 12, 2875–2892 (2022). https://doi.org/10.1007/s13346-022-01151-4

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