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Assessment of irritative potential, citotoxicity and retention of nanocarriers in mammary tissue aiming the breast cancer localized treatment

Grant number: 16/23590-6
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): March 01, 2017
Effective date (End): October 31, 2017
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal researcher:Luciana Biagini Lopes
Grantee:Amanda Migotto
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:13/16617-7 - Nanostructured systems for topical delivery and co-localization of chemopreventive and chemoterapeutic agents in the skin and breast tissue, AP.JP

Abstract

Breast cancer is one of the most prevailing tumors worldwide. Among its types, ductal carcinoma in situ (DCIS) currently represents 20-25% of diagnosed cases. Treatment options are invasive and/or have limited action spectrum, mainly represented by surgery, followed by radiotherapy and/or oral tamoxifen. However, this treatment standard has been questioned especially when it comes to low risk DCIS, which has prompted the search for new alternatives for local treatment. Here we propose the intraductal administration of nanocarriers containing C6 Ceramide in an attempt to increase drug concentration at therapeutic target, therefore attenuating adverse effects by reducing systemic exposure. We have developed a cationic oil-in-water nanoemulsion with biadhesive properties conferred by chitosan-modified surface. Based on this fact, the goal of this study is to evaluate cytotoxicity of the formulation and possible synergy or additive effects of ceramide and tributyrin, an oil phase component, included in the formulation for being a pro-drug of butyric acid and thus, cytotoxic against several tumor lineages. In addition, we propose to evaluate the formulation irritation potential, as well as in vivo local retention, key factors to predict nanoemulsion therapeutic potential and its future clinical applicability. (AU)

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