Chemoprevention of Breast Cancer by Transdermal Delivery of α-Santalol through Breast Skin and Mammary Papilla (Nipple)

Purpose Almost all breast cancers originate from epithelial cells lining the milk ducts in the breast. To this end, the study investigated the feasibility of localized transdermal delivery of alpha-santalol, a natural chemopreventive agent to the breast. Methods Different alpha-santalol formulations (cream, solution and microemulsion) were developed and the in vitro permeability was studied using excised animal (porcine and rat) and human breast skin/mammary papilla (nipple). The in vivo biodistribution and efficacy studies were conducted in female rats. A chemical carcinogenesis model of breast cancer was used for the efficacy studies. Results Phospholipid based alpha-santalol microemulsion showed the highest penetration through the nipple and breast skin. Delivery of alpha-santalol through the entire breast (breast skin and nipple) in vivo in rats resulted in significantly higher concentration in the mammary gland compared to transdermal delivery through the breast skin or nipple. There was no measurable alpha-santalol concentration in the blood. Transdermal delivery of alpha-santalol reduced the tumor incidence and tumor multiplicity. Furthermore, the tumor size was significantly reduced with alpha-santalol treatment. Conclusions The findings from this study demonstrate the feasibility of localized transdermal delivery of alpha-santalol for chemoprevention of breast cancer.