title: Transpapillary (Nipple) Delivery of Macromolecules to the Breast: Proof of Concept Study.
abstract: Localized drug delivery to the breast can maximize drug concentration at the target site and minimize systemic drug distribution. To this end, the study explored the feasibility of delivering macromolecules to the breast through mammary papilla (nipple). The in vitro penetration of model macromolecules (inulin, dextran, ovalbumin, and bovine serum albumin) varying in molecular weight from 5 to 67 kDa was studied using excised porcine and human mammary papilla. The penetration of macromolecules decreased with increase in molecular weight. The penetration of the macromolecules was significantly higher through the mammary papilla in comparison to breast skin. In vitro penetration of the macromolecules was similar in human and porcine mammary papilla. Iontophoresis was used to enhance the transport of bovine serum albumin (BSA) through the mammary papilla. The flux and cumulative amount permeated was increased by 2- to 4-fold by iontophoresis. The macromolecules were transported through the ducts and the surrounding connective tissue in the mammary papilla. Overall, the results from this study for the first time demonstrate the feasibility of delivering macromolecules through the mammary papilla. These findings have implications for developing safe and effective localized therapeutic approaches for breast cancer.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University , Brookings, South Dakota 57007, United States.
authors.forename: Kaushalkumar
authors.initials: K
authors.lastname: Dave
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University , Brookings, South Dakota 57007, United States.
authors.forename: Fahd M
authors.initials: FM
authors.lastname: Alsharif
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University , Brookings, South Dakota 57007, United States.
authors.forename: Omathanu
authors.initials: O
authors.lastname: Perumal
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001940:Breast / Q000378:metabolism*; D003911:Dextrans / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007444:Inulin / Q000378:metabolism; D007478:Iontophoresis; D008856:Microscopy, Fluorescence; D008970:Molecular Weight; D009558:Nipples / Q000378:metabolism*; D010047:Ovalbumin / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013552:Swine
chemical_list: D003911:Dextrans; D012710:Serum Albumin, Bovine; D007444:Inulin; D010047:Ovalbumin
keywords: BSA; breast cancer; iontophoresis; macromolecules; mammary papilla; nipple; topical; transdermal