Breast cancer, one of the most frequent causes of death among women, accounts for about 25% of new cases annually in Brazil and worldwide. The ductal carcinoma in situ corresponds to approximately 25% of the diagnosed types of breast cancer. Due to the risk to originate invasive cancer, these tumors are usually treated with surgery (conservative and / or radical) followed by radiotherapy and/or oral tamoxifen. However, several groups have questioned the need for this aggressive treatment for low grade lesions, which has prompted the interest and in novel strategies for localized treatment. In this project, we propose the development of bioadhesive nanocarriers for intraductal administration of the drug piplartine as a new strategy for the treatment of ductal carcinoma in situ (DCIS). Piplartine (piperlongumine) is an alkaloid / amide component of Piper species that has significant cytotoxic and antiproliferative activity in several tumor cell lines. Due to the absence of specific formulations for intraductal drug administration the lack of effective therapeutic alternatives capable of locating drugs in the breast tissue avoiding systemic exposure and incidence of side effects, we propose to evaluate cationic, bioadhesive nanocarriers for localization of the active agent piplartine in the breast. The positive charge of the systems will be conferred by surface modification with chitosan or cetylpyridine chloride, while and the bioadhesive potential by hyaluronic acid or chitosan. The selected formulations wii be evaluated for particle size, zeta potential, rheological stability and irritation potential. Subsequently, we will study drug retention in the breast, evaluation of the cytotoxic effects in tumor cell lines in bi and tridimensional culture and animal models of breast cancer.
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