Evaluation of the biological activity of vectorized nanostructured lipid systems for delivery of rapamycin in animal model and breast cancer cell line

• Grant number: 19/18211-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: November 30, 2019
• End date: November 29, 2020
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Marlus Chorilli
• Grantee: Camila Fernanda Rodero
• Supervisor: Juan M. Irache
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: Universidad de Navarra, Spain
• Associated to the scholarship: 17/22758-3 - Evaluation of the nanostructured lipid carriers potential functionalized with folic acid incorporated with rapamycin for breast cancer treatment , BP.DR

Abstract

Breast cancer can be defined as a malignant tumor of epithelial cells that develops in the breast, being considered the second most common type of cancer in the world, with estimated worldwide incidence of approximately 1.6 million of new cases per year. Among the drugs used in therapy, rapamycin stands out, traditionally used as an immunosuppressant and has demonstrated a potent activity against breast cancer, since it is capable of inhibiting the mTOR protein, which is located in the cytoplasm of the cells Regulating growth and progression in the cell cycle. However, it is a lipophilic drug, suffers sequestration by erythrocytes and has chemical instability, factors that compromise the bioavailability. Thus, its incorporation into NLC functionalized with folic acid demonstrates to be an interesting option to enable its use, since these systems can protect the drug from degradation, incorporate hydrophobic drugs, increase the time of Place of action, provide slower and sustained action. The functionalization of the NLC with folic acid allows the release of the drug at the target site by binding in folate receptors that are expressed in low quantity by normal cells and in large quantities by a variety of tumor cells (ovary, Prostate and breast), decreasing the side effects of treatment. In view of the above, the objective of the present work is to develop and characterize NLC functionalized with folic acid for the incorporation of rapamycin and to evaluate its potential in the treatment of breast cancer. The uptake and cell location of the systems will be evaluated by confocal microscopy and flow cytometry. Finally, the carriers will be evaluated for efficacy in breast cancer therapy by cytotoxicity studies and animal models. (AU)