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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR PHARMACEUTICS; v. 18, n. 9, p. 3401-3417, SEP 6 2021.
• Citações Web of Science: 0

Resumo

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)

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