Nanostructured lipid carriers for co-encapsulation and sustained release of fenretinide and perillyl alcohol in the mammary tissue aiming at prevention of development and recurrences of Breast Cancer

• Grant number: 22/00997-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: December 01, 2022
• End date: January 31, 2027
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Luciana Biagini Lopes
• Grantee: Isabella Draszesski Malagó
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/13877-1 - Nanocarriers for localized treatment and chemoprevention of breast tumors, AP.JP2
• Associated scholarship(s): 25/04793-2 - Evaluation of chondroitin sulfate/hyaluronic acid blended hydrogels as a novel subcutaneous drug and peptide delivery system, BE.EP.DD

Abstract

In spite of the high incidence of breast cancer, there are few pharmacological strategies available to prevent the development of tumors and recurrences in the high risk population. The available strategies are used systemically and provoke severe adverse effects, like fatigue, reduction of bone density, thromboembolism, cardiovascular symptoms and increased risk of developing other tumors, besides being specific for hormone-dependent tumors. In a previous Scientific Initiation project, we have developed nanostructured lipid carriers (NLC) for fenretinide and perillyl alcohol (POH) release in the mammary tissue as a new pharmacological strategy to reduce breast cancer incidence and recurrence. As from the results, we now propose to expand the characterization and biological evaluation of the developed nanocarriers. Effects of the association between distinct concentrations of the active compounds on the NLC characteristics, its ability to prolong the in vitro release and its cellular effects on T-47D, MCF-7, MDA-MB-231 and MCF-10A cell lines will be evaluated through cytotoxicity, cytostaticity and invasion studies. After optimization of the nanocarrier, cellular uptake and in vitro tumor penetration will be assessed. Spreading of the formulation in tissue will be estimated by two methods, using hydroxypropyl cellulose gel and porcine ear skin. An animal model of induced carcinogenesis, added to hystological analysis, will be used to study the distribution of the compounds in vivo, verifying the system capability of promoting minimal systemic exposure associated to efficacy in preventing breast tumors. (AU)