Multifunctional nanostructured lipid carrier containing 5-fluorouracil and siRNA for treatment of skin cancer

• Grant number: 17/04335-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2017
• End date: February 28, 2019
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Maria Vitória Lopes Badra Bentley
• Grantee: Juliana dos Santos Rosa
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Skin cancer is the most frequent type of cancer in Brazil, accounting for between 25% and 30% of registered cases of malignancy. The three most common types of skin cancer are basal cell and squamous cell carcinoma (non-melanoma types) and malignant cutaneous melanoma (melanoma type). The various therapeutic strategies for topical treatment of skin cancer, although effective in some cases, still have limitations due to the low penetration of drugs in the skin and inefficacy of drugs in single therapies, given the complex cascade of events that occur in the pathological process Of cancer. Thus, multifunctional release systems, formed by nanocarriers and the association of therapeutic molecules acting on different cancer targets, represent an innovative and important therapeutic strategy.In view of the above, the present project aims at the development of a multifunctional system that associates antineoplastic therapy and gene silencing therapy. Nanostructured lipid nanocarriers (CLNs) associated with two types of drugs, 5-Fluorouracil (5-FU) and a gene silencer, which will act on different therapeutic targets in a synergistic way in the treatment of cancer, will be developed.5-FU is a pyrimidine analog, in this way, interferes with the synthesis of DNA. BCL-2 protein is an anti-apoptotic protein and is overexpressed in several types of cancer. The gene silencing of this protein may be promoted by a specific siRNA, which will be an event of gene repression through the degradation of messenger RNA (mRNA). The studies will involve the standardization of techniques for obtaining CLNs, incorporation / complexation of the drugs, physico-chemical and morphological characterization of the obtained systems, skin penetration in vitro in animal skin model, cellular cytotoxicity studies, cellular uptake and transfection and Finally the evaluation of efficacy in cancer cell lines.The experimental strategy suggested in this proposal will result in a technological and therapeutic feasibility study of multifunctional CLNs for topical skin cancer therapy. (AU)