Breast cancer is the second most incident tumor in the world, presenting high mortality index. Nowadays, preventive actions include risk factors control, mammographic screening, preventive mastectomy and few chemopreventive pharmacological strategies associated with low adhesion of patients due to the serious adverse effects. Studies have shown that retinoids are capable of inhibiting mammary tumors in animals and humans for their important role in regulating cell growth and differentiation. Fenretinide is derivated of retinoic acid and, for its ability to accumulate in breast tissue, is considered promising for chemoprevention. However, in addition to presenting serious systemic adverse effects, its high lipophilicity results in low oral bioavailability. To overcome these limitations and allow the use of this drug in chemoprevention, the present study aims the development of a nanostructured system for sustained release of Fenretinide in the breast tissue. Specifically, it is proposed the development of an economically viable fluid precursor formulation which, through subcutaneous administration and absorption of water in situ, turning into a hexagonal phase capable of sustaining the local release of the drug. Precursor formulations will be developed through the combination of monolein, phosphatidylcholine, propyleneglycol, tricaprilin and water. The affinity between composition and formed phase, intumescence kinetics and in vitro release will be studied in order to evaluate how the composition affects the properties of the system. A formulation will then be selected (optimized formulation) for evaluation of its formation and ability to sustain the release of compounds in vivo. Its efficacy and selectivity will be evaluated in 2D and 3D models, by studying its influence on viability and proliferation of tumor and non-transformed cells. With this study, we aim to contribute to the development of a more effective and well accepted platform for the chemoprevention of breast cancer. (AU)
News published in Agência FAPESP Newsletter about the scholarship:
JUNQUEIRA GARCIA, MARIA TERESA;
GONCALVES, THALITA PEDRALINO;
MARTINS, ERICKA SAO FELIX;
MARTINS, TEREZA SILVA;
DE ABREU FANTINI, MARCIA CARVALHO;
REGAZI MINARINI, PAULO ROBERTO;
FERNANDEZ, SANDRA COSTA;
SALATA, GIOVANNA CASSONE;
LOPES, LUCIANA BIAGINI.
Improvement of cutaneous delivery of methylene blue by liquid crystals.
International Journal of Pharmaceutics,
Web of Science Citations: 5.
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