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Evaluation of an Anhydrous Permeation-Enhancing Vehicle for Percutaneous Absorption of Hormones

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Abstract

The efficiency and safety of hormone delivery through the skin partly depend on the appropriate choice of vehicle and the type of formulation. The present study reports the skin cytotoxicity, irritancy, and safety of a newly developed anhydrous permeation-enhancing base (APEB) and the percutaneous absorption of progesterone, testosterone, estriol, and estradiol in APEB formulations. Using the human skin EpiDerm model, cell death was not observed after 4 h of exposure to APEB and was 48% after 24 h, indicating its mild to non-irritating property. APEB did not change the expression level of skin cell proliferation markers including PCNA, MCL-1, iNOS, and NFκB proteins, and apoptosis was minimal after 8-h exposure. The in vivo skin irritation and sensitization evaluation of APEB using a Human Repeat Insult Patch Test showed no adverse reaction of any kind during the course of the study. These results indicate the safety of APEB on skin tissues. The hormone percutaneous absorption was performed using human cadaver abdomen skin tissues and the Franz diffusion system, and hormone concentrations were determined by ELISA. Absorption was observed as early as 2 h of application and accumulated after 24 h to 2851 ± 66 ng/cm2, 2338 ± 594 ng/cm2, 55 ± 25 ng/cm2, and 341 ± 122 ng/cm2 for progesterone, testosterone, estriol, and estradiol, respectively. A steady flux rate of absorption of the hormones was observed within 24 h of application. These results suggest that APEB can be used as a vehicle to deliver these hormones through the skin and into the bloodstream for hormone replacement therapy.

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Acknowledgements

The authors would like to thank BioScreen Testing Service, Inc. (Torrance, CA) for conducting HRIPT for skin irritation and sensitization.

Funding

This work was supported by Professional Compounding Centers of America (PCCA), the manufacturer of APEB and VersaBase Cream.

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Authors and Affiliations

  1. Professional Compounding Centers of America (PCCA), 9901 South Wilcrest Drive, Houston, Texas, 77099, United States of America

    Guiyun Song, Daniel Banov, Hui Song, Yi Liu, Kendice Ip & August S. Bassani

  2. Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, United States of America

    Benigno C. Valdez

Authors
  1. Guiyun Song
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  2. Daniel Banov
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  3. Hui Song
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  4. Yi Liu
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  5. Kendice Ip
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  6. August S. Bassani
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  7. Benigno C. Valdez
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Contributions

G. Song, K. Ip, H. Song, and B. Valdez contributed to the conception and design of the study and analysis and interpretation of data. G. Song, Y. Liu, and B. Valdez wrote the manuscript. D. Banov and A. Bassani were responsible for the research approach, funding, analysis of data, and critical revision of the article. All of the authors contributed to the final version of the manuscript.

Corresponding author

Correspondence to Guiyun Song.

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Conflict of Interest

The authors G. Song, D. Banov, H, Song, Y. Liu, K. Ip, and A. Bassani are employees of PCCA, the manufacturer of the proprietary bases VersaBase® Cream (VBC) and anhydrous permeation-enhancing base (APEB).

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Song, G., Banov, D., Song, H. et al. Evaluation of an Anhydrous Permeation-Enhancing Vehicle for Percutaneous Absorption of Hormones. AAPS PharmSciTech 23, 198 (2022). https://doi.org/10.1208/s12249-022-02352-3

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