Abstract
Considering the high incidence of breast tumors and the lack of strategies for local management of non-invasive cases, as well as effective, safe and well-accepted chemoprevention alternatives for high-risk population, we propose the development of nanotechnology-based strategies to fill this gap. To increase treatment efficacy, we propose to co-encapsulate combinations of cytotoxic, cicloxigenase-2 inhibitors and anti-proliferative agents, which may potentiate each other effects due to interference with multiple signaling pathways. We will develop nanocarriers for the intraductal, topical and subcutaneous routes, aiming local application to the breast tissue. Nanoemulsions, polyelectrolyte nanoparticles, nanodispersions and microemulsions will be developed, and their diameter, zeta potential, rheological, bioadhesive and swelling properties will be characterized. Subsequently, we will study the influence of composition on skin permeability, skin penetration and percutaneous delivery, irritation potential, formulation residence and drug delivery in the mammary tissue. The influence of nanoencapsulation and association of drugs on cytotoxicity and anti-proliferative effects, as well as selective effects of drugs and formulations against cancer cells will be assessed in 2D cultures and 3D multicellular spheroids. Results from these studies will enable selection of formulations for assessment of in vivo efficacy in models of breast cancer. (AU)
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