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• W4381952104 endingPage "123175" @default.
• W4381952104 startingPage "123175" @default.
• W4381952104 abstract "Breast cancer (BC) has surpassed lung cancer as the most diagnosed cancer and, in terms of mortality, is the fifth leading cause with 684,996 new deaths (6.7% of all cancer-related deaths) and the highest mortality amongst all cancers (15.5%) in women. Selective estrogen-receptor modulators (SERMs) have been used for the last thirty years for estrogen receptor-positive (ER+) BC prevention and treatment. Tamoxifen (TAM), the most widely used SERM, is orally administered and its long-term oral administration has been associated to toxicity and adverse side effects. Endoxifen (EDX) is one of the known active metabolites of TAM, with an affinity to ERα 100 times higher than TAM. Furthermore, EDX has shown antiproliferative activity against the ER+ BC cell line MCF-7. Alternative administration routes that avoid the metabolic processing of TAM seem an appealing alternative to its oral administration. With this aim, we have prepared a polymeric gel-like solution of Pluronic® F127 as vehicle for topical administration of EDX. In order to shed light on the potential clinical use of this formulation, we have compared it with the standard pharmaceutical form, i.e. orally administered TAM. The biodistribution, antitumor efficacy and toxic effects of topical EDX and oral TAM were evaluated in ER+ tumor xenograft athymic nu/nu mouse models. The results showed a statistically significant antitumor effect and reduced toxicity of topical EDX as compared to oral TAM or empty F127 gel. This novel administration route of SERMs could also have a strong impact in the prevention of BC at early development stages and could help to ameliorate the mortality and morbidity related to this disease." @default.
• W4381952104 created "2023-06-26" @default.
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• W4381952104 date "2023-07-01" @default.
• W4381952104 modified "2023-10-18" @default.
• W4381952104 title "Evaluation of a polymeric topical formulation of Endoxifen in an estrogen receptor positive breast cancer murine model" @default.
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• W4381952104 doi "https://doi.org/10.1016/j.ijpharm.2023.123175" @default.
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