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Influence of Hydroalcoholic Vehicle on In Vitro Transport of 4-Hydroxy Tamoxifen Through the Mammary Papilla (Nipple)

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Abstract

Majority of breast cancers originate from epithelial cells in the duct and lobules in the breast. Current systemic treatments for breast cancer are associated with significant systemic side effects, thus warranting localized drug delivery approaches. The aim of this study was to investigate the influence of hydroalcoholic vehicle on topical delivery of 4-hydroxy tamoxifen (4-HT) through the mammary papilla (nipple). The in vitro permeability of 4-HT through porcine mammary papilla was studied using different hydroalcoholic vehicles (0, 33.33, and 66.66% alcohol). Nile red was used as a model lipophilic dye to characterize the drug transport pathway in the mammary papilla. The penetration of 4-HT through the mammary papilla increased with increase in alcohol concentration in the vehicle. The solubility of 4-HT was enhanced by increasing alcohol concentration in the vehicle. On the other hand, the epidermis/vehicle partition coefficient decreased with increase in alcohol concentration. The mammary papilla served as a depot and slowly released 4-HT into the receptor medium. Highest drug penetration was observed with saturated drug solution in 66.66% alcohol, and 4-HT levels were comparable to IC50 value of 4-HT. Results from this study demonstrate the possibility of using mammary papilla as a potential route for direct delivery of 4-HT to the breast.

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Acknowledgments

Financial and research support for Fahd M. Alsharif was provided by the Egyptian Cultural and Educational Bureau, Washington DC, USA. This work was funded by the South Dakota Governor’s 2010 Translational Cancer Research Center. Porcine tissues were provided by Dr. Kelley Bruns and Adam Rhody from the Department of Animal Science, South Dakota State University, Brookings, SD, USA.

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Author notes

  1. Kaushalkumar Dave

    Present address: Division of Biopharmaceutics, Office of New Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, South Dakota, 57007, USA

    Fahd M. Alsharif, Kaushalkumar Dave & Omathanu Perumal

  2. Department of Pharmaceutics and Ind. Pharmacy, College of Pharmacy, Al-Azhar University, Assiut, Egypt

    Fahd M. Alsharif, Khaled I. Saleh & Mohamed A. Amin

  3. Department of Pharmaceutics and Ind. Pharmacy, College of Pharmacy, Al-Azhar University, Cairo, Egypt

    Ahmed M. Samy

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  1. Fahd M. Alsharif
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Correspondence to Omathanu Perumal.

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Alsharif, F.M., Dave, K., Samy, A.M. et al. Influence of Hydroalcoholic Vehicle on In Vitro Transport of 4-Hydroxy Tamoxifen Through the Mammary Papilla (Nipple). AAPS PharmSciTech 18, 1366–1373 (2017). https://doi.org/10.1208/s12249-016-0608-x

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  • DOI: https://doi.org/10.1208/s12249-016-0608-x

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