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THERAPEUTICAL EFFECTIVENESS OF ACETYLEUGENOL NANOCAPSULES IN A EXPERIMENTAL MODEL OF MELANOMA IN VIVO

Grant number: 12/01257-2
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2012
Effective date (End): March 31, 2013
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal researcher:Sandra Helena Poliselli Farsky
Grantee:Celina Goulart Bexiga
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Nanotechnology has being evidenced in many technological sectors in recent years, including the pharmaceutical, especially for the treatment of cancer, since the drugs currently available to control this disease cause serious adverse effects to the patients. Thus, nanoparticulated systems are becoming important for providing the vectorization of drugs to specific targets, decreasing the dose required for the therapeutical effect and, consequently, the toxicity. However, the mechanisms involved in the therapeutical effectiveness of these compounds need to be better understood. Eugenol is a natural compound which displays antiproliferative and pro-apoptotic activities in different types of cancer cells. Since acetyleugenol showed greater cytotoxicity than eugenol, this study aims to evaluate the effects of acetyleugenol (ACEU) and its nanocapsule formulation (NcACEU) in an in vivo experimental model of melanoma. For this, murine melanoma cells (B16F10) will be injected subcutaneously in the dorsal region of C57B16 mice. The animals will be treated with NcACEU or with ACEU (solution), intraperitoneally (i.p.), at doses of 20 and 100 mg / kg / day, or with their respective controls (Nc, the ACEU vehicle or saline) from the third to the tenth day after the melanoma induction. At the 10th day, the survival rate, tumor growth and the weight of mice will be analysed. Following, animals will be killed and blood will be collected to the analysis of cells (total and differential) and to quantify creatinine, urea, gammaGT, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes; tumor tissue will be collected to the quantification of inflammatory mediators (nitric oxide (NO), interleukin 10 (IL10), prostaglandin E2 (PGE2) and tumor necrosis factor (TNF±)) and the vascular endothelial growth factor (VEGF); liver, kidneys, lungs, lymph nodes and dorsal region will be obtained to histological analysis. This work is part of a larger project of our group that has evaluated the therapeutical effectiveness of nanodrugs, in collaboration with the Guterres' and Pohlmann's research groups, professors at the Federal University of Rio Grande do Sul (UFRGS).