title: Influence of Hydroalcoholic Vehicle on In Vitro Transport of 4-Hydroxy Tamoxifen Through the Mammary Papilla (Nipple).
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 IC50value 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.
authors: Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, South Dakota, 57007, USA.|Department of Pharmaceutics and Ind. Pharmacy, College of Pharmacy, Al-Azhar University, Assiut, Egypt.
authors: Fahd M
authors: FM
authors: Alsharif
authors: Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, South Dakota, 57007, USA.|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: Kaushalkumar
authors: K
authors: Dave
authors: Department of Pharmaceutics and Ind. Pharmacy, College of Pharmacy, Al-Azhar University, Cairo, Egypt.
authors: Ahmed M
authors: AM
authors: Samy
authors: Department of Pharmaceutics and Ind. Pharmacy, College of Pharmacy, Al-Azhar University, Assiut, Egypt.
authors: Khaled I
authors: KI
authors: Saleh
authors: Department of Pharmaceutics and Ind. Pharmacy, College of Pharmacy, Al-Azhar University, Assiut, Egypt.
authors: Mohamed A
authors: MA
authors: Amin
authors: Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, South Dakota, 57007, USA. Omathanu.perumal@sdstate.edu.
authors: Omathanu
authors: O
authors: Perumal
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy; D016503:Drug Delivery Systems; D005260:Female; D009558:Nipples / Q000378:metabolism*; D014677:Pharmaceutical Vehicles; D012995:Solubility; D013552:Swine; D013629:Tamoxifen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D014677:Pharmaceutical Vehicles; D013629:Tamoxifen; C016601:afimoxifene
keywords: 4-hydroxy tamoxifen; breast cancer; hydroalcoholic vehicle; mammary papilla; topical delivery