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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Microemulsion for Prolonged Release of Fenretinide in the Mammary Tissue and Prevention of Breast Cancer Development

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Salata, Giovanna Cassone [1] ; Malago, Isabella D. [1] ; Carvalho Dartora, Vanessa F. M. [1] ; Marcal Pessoa, Ana Flavia [2] ; de Abreu Fantini, Marcia Carvalho [3] ; Costa, Soraia K. P. [1] ; Machado-Neto, Joao Agostinho [1] ; Lopes, Luciana B. [1]
Total Authors: 8
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Farmacol, BR-05508000 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Fac Med, Dept Cirurgia, LIM26, BR-01246903 Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Inst Fis, Dept Fis Aplicada, BR-05508090 Sao Paulo, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: MOLECULAR PHARMACEUTICS; v. 18, n. 9, p. 3401-3417, SEP 6 2021.
Web of Science Citations: 0

The need of pharmacological strategies to preclude breast cancer development motivated us to develop a nonaqueous microemulsion (ME) capable of forming a depot after administration in the mammary tissue and uptake of interstitial fluids for prolonged release of the retinoid fenretinide. The selected ME was composed of phosphatidylcholine/tricaprylin/propylene glycol (45:5:50, w/w/w) and presented a droplet diameter of 175.3 +/- 8.9 nm. Upon water uptake, the ME transformed successively into a lamellar phase, gel, and a lamellar phase-containing emulsion in vitro as the water content increased and released 30% of fenretinide in vitro after 9 days. Consistent with the slow release, the ME formed a depot in cell cultures and increased fenretinide IC50 values by 68.3- and 13.2-fold in MCF-7 and T-47D cells compared to a solution, respectively. At non-cytotoxic concentrations, the ME reduced T-47D cell migration by 75.9% and spheroid growth, resulting in similar to 30% smaller structures. The depot formed in vivo prolonged a fluorochrome release for 30 days without producing any sings of local irritation. In a preclinical model of chemically induced carcinogenesis, ME administration every 3 weeks for 3 months significantly reduced (4.7-fold) the incidence of breast tumors and increased type II collagen expression, which might contribute to limit spreading. These promising results support the potential ME applicability as a preventive therapy of breast cancer. (AU)

FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
Grantee:Maria Vitória Lopes Badra Bentley
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 19/23864-7 - Comprehensive analysis of genomic data for identification and validation of novel therapeutic targets involved in cellular cytoskeleton regulation in acute Leukemia
Grantee:João Agostinho Machado Neto
Support Opportunities: Regular Research Grants
FAPESP's process: 16/06146-5 - Bioavailability of Hydrogen Sulfide in a topical nanoformulation in experimental psoriasis
Grantee:Soraia Katia Pereira Costa
Support Opportunities: Regular Research Grants
FAPESP's process: 17/23213-0 - Biorresponsive systems for sustained drug release and breast cancer chemoprevention
Grantee:Giovanna Cassone Salata
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 18/13877-1 - Nanocarriers for localized treatment and chemoprevention of breast tumors
Grantee:Luciana Biagini Lopes
Support Opportunities: Research Grants - Young Investigators Grants - Phase 2