Abstract P1-10-16: In vitro delivery of model fluorescent dyes through the mammary papilla

Abstract

Abstract In the United States, 100,000 women each year are diagnosed with atypical hyperplasia (AH), significantly increasing their risk of developing breast cancer. However, only 40% of patients accept breast cancer preventive treatment, in part, due to systemic side effects. The localization of pre-cancerous cells within the ducts or lobules of the breast permits a local treatment strategy employing the innate mammary ducts. This expansive tree-like structure extends throughout the entire breast and may serve as a conduit for local delivery of therapeutics, thereby minimizing side effects associated with current preventive treatment strategies. This study examines how lipophilicity influences diffusion through porcine tissue using a model hydrophilic dye, Sulforhodamine B (SRB), and a model lipophilic dye, Nile Red (NR). Porcine nipple or skin tissue was positioned in a Franz diffusion cell and the formulations were applied topically. With equivalent dye concentrations applied to the donor surface, we noted no significant difference in total dye permeation when comparing diffusion through skin versus nipple tissue or when comparing SRB versus NR after 48 hours. However, the diffusion coefficient for both NR and SRB through the nipple was almost 700-fold greater compared to through the skin indicating improved drug delivery via the nipple. Additionally, after 48 hours there was significantly higher retention of SRB in the nipple and skin compared to NR. When we further looked at the distribution of each dye within the nipple using fluorescence microscopy, we saw a distinction in the localization of each dye. Fluorescence micrographs show that lipophilic NR is retained within the ducts while the hydrophilic SRB diffuses throughout the entire tissue section, suggesting that hydrophobicity impacts the ability of molecules to diffuse from the duct into the surrounding tissue. This suggests that lipophilic carriers may be effective for delivery of cancer therapeutics or preventative agents targeting the mammary ducts, where AH is localized. Citation Format: Kurtz SL, Lawson LB. In vitro delivery of model fluorescent dyes through the mammary papilla [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-10-16.