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

被引：9
作者：
Alsharif, Fahd M. [1 ,2 ]
Dave, Kaushalkumar [1 ,3 ]
Samy, Ahmed M. [4 ]
Saleh, Khaled I. [2 ]
Amin, Mohamed A. [2 ]
Perumal, Omathanu [1 ]
机构：
[1] South Dakota State Univ, Coll Pharm, Dept Pharmaceut Sci, Brookings, SD 57007 USA
[2] Al Azhar Univ, Coll Pharm, Dept Pharmaceut & Ind Pharm, Assiut, Egypt
[3] US FDA, Div Biopharmaceut, Off New Drug Prod, Off Pharmaceut Qual,Ctr Drug Evaluat & Res, Silver Spring, MD USA
[4] Al Azhar Univ, Dept Pharmaceut & Ind Pharm, Coll Pharm, Cairo, Egypt
来源：
AAPS PHARMSCITECH | 2017年 / 18卷 / 04期
关键词：
4-hydroxy tamoxifen; breast cancer; hydroalcoholic vehicle; mammary papilla; topical delivery; ESTROGEN-RECEPTOR MODULATORS; NORMAL BREAST-TISSUE; STRATUM-CORNEUM; SKIN PERMEATION; CANCER CELLS; PREVENTION; ENDOXIFEN; ESTRADIOL; THERAPY; WOMEN;
D O I：
10.1208/s12249-016-0608-x
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
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 4hydroxy 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.
引用
收藏
页码：1366 / 1373
页数：8
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