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Biorresponsive systems for sustained drug release and breast cancer chemoprevention

Grant number: 17/23213-0
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2018
Effective date (End): February 29, 2020
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Luciana Biagini Lopes
Grantee:Giovanna Cassone Salata
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:13/16617-7 - Nanostructured systems for topical delivery and co-localization of chemopreventive and chemoterapeutic agents in the skin and breast tissue, AP.JP

Abstract

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)

Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ALEXSANDRA CONCEIÇÃO APOLINÁRIO; GIOVANNA CASSONE SALATA; ARTHUR F. R. BIANCO; CLAUDIO FUKUMORI; LUCIANA BIAGINI LOPES. ABRINDO A CAIXA DE PANDORA DOS NANOMEDICAMENTOS: HÁ REALMENTE MUITO MAIS ‘ESPAÇO LÁ EMBAIXO’. Química Nova, v. 43, n. 2, p. 212-225, Fev. 2020.
CARVALHO, VANESSA F. M.; SALATA, GIOVANNA C.; DE MATOS, JENYFFER K. R.; COSTA-FERNANDEZ, SANDRA; CHORILLI, MARLUS; STEINER, ALEXANDRE A.; DE ARAUJO, GABRIEL L. B.; SILVEIRA, EDILBERTO R.; COSTA-LOTUFO, V, LETICIA; LOPES, LUCIANA B. Optimization of composition and obtainment parameters of biocompatible nanoemulsions intended for intraductal administration of piplartine (piperlongumine) and mammary tissue targeting. International Journal of Pharmaceutics, v. 567, AUG 15 2019. Web of Science Citations: 2.
MOJEIKO, GABRIELA; DE BRITO, MOACIR; SALATA, GIOVANNA C.; LOPES, LUCIANA B. Combination of microneedles and microemulsions to increase celecoxib topical delivery for potential application in chemoprevention of breast cancer. International Journal of Pharmaceutics, v. 560, p. 365-376, APR 5 2019. Web of Science Citations: 3.
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, v. 548, n. 1, p. 454-465, SEP 2018. Web of Science Citations: 5.

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