Transpapillary iontophoretic delivery of resveratrol loaded transfersomes for localized delivery to breast cancer

Localized drug delivery to the breast tissues is an area of interest as a potential route to ensure site-specific drug delivery. Transpapillary delivery via the mammary papilla has advantages as most breast tumors arise from the milk ducts. The present study explored the plausibility of transpapillary delivery of a phytochemical, resveratrol (RVT), for breast cancer treatment. RVT was encapsulated within the transfersomes (RVT-TRF) to enable a sustained release of the drug using the biomaterial soya phosphatidylcholine (SPC). Iontophoresis was applied to further accelerate the penetration of the RVT-TRF across the mammary papilla to the breast tissue. The RVT-TRF development was optimized by the Design of Experiments (DoE) approach. The in vitro transpapillary iontophoresis study on porcine mammary papilla showed an enhanced penetration of RVT-TRF when compared to passive diffusion. The transpapillary delivery was further confirmed from the in vitro fluorescent microscopy study using FITC conjugated RVT-TRF. The optimized RVT-TRF delivered via transpapillary route showed a higher C_max and AUC when compared to pure RVT given orally. A significant reduction in the tumor volume and the serum biomarker CA 15-3, when evaluated in a chemically induced breast cancer rat model, provided evidence of the effectiveness of the developed formulation when delivered locally via transpapillary route compared to the oral route. Thus the developed RVT-TRF administered via transpapillary iontophoresis technique is a promising strategy enabling a localized delivery for effective breast cancer therapy.