Development and application of multifunctional nanocarriers for intraductal delivery of chemotherapy aiming at Breast Cancer treatment

Abstract

In this project, we propose the development and evaluation of nanoemulsions functionalized with hyaluronic acid for localized intraductal treatment of Ductal Carcinoma In Situ and other breast lesions (which increase the risk for development of invasive forms of Breast Cancer) combining efficacy, selectivity and reduction of systemic adverse effects of chemotherapy. In order to potentialize the cytotoxic effects and reduce resistance, we propose the co-incorporation of 3 active compounds: (i) paclitaxel, a cytotoxic agent, effective in various types of tumors, (ii) elacridar, a potent inhibitor of efflux transporter P-gp, associated with the development of resistance to chemotherapy (including paclitaxel) and (iii) perillyl alcohol, a monoterpene capable of potentializing the cytotoxic effect of other compounds. After nanoemulsion obtainment and characterization, we will assess the cellular effects and application of the nanocarriers in 2D and 3D models, cell uptake, mammary retention and efficacy in an animal model of chemically induced carcinogenesis. With this project, we aim to contribute to the development of a localized, more effective and safer platform for Breast Cancer treatment. (AU)