The need of pharmacological strategies to preclude breast cancer development motivated us to develop a non-aqueous 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 ∼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.

中文翻译：

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用于延长乳腺组织中芬维A胺释放和预防乳腺癌发展的微乳

预防乳腺癌发展的药理学策略的需要促使我们开发一种非水性微乳 (ME)，该微乳 (ME) 能够在乳腺组织中给药后形成储库，并吸收间质液以延长类维生素 A 芬维A 胺的释放。选定的 ME 由磷脂酰胆碱/三辛精/丙二醇 (45:5:50, w/w/w) 组成，液滴直径为 175.3 ± 8.9 nm。吸水后，随着水含量的增加，ME在体外依次转变为层状相、凝胶和含有层状相的乳液，并在 9 天后在体外释放出 30% 的芬维A胺。与缓慢释放一致，ME 在细胞培养物中形成了一个贮库并增加了芬维A胺 IC ₅₀与溶液相比，MCF-7 和 T-47D 细胞中的值分别增加了 68.3 倍和 13.2 倍。在非细胞毒性浓度下，ME 减少了 75.9% 的 T-47D 细胞迁移和球体生长，导致约 30% 的结构更小。体内形成的贮库将荧光染料的释放时间延长了 30 天，而不会产生任何局部刺激。在化学诱导致癌作用的临床前模型中，ME 给药每 3 周持续 3 个月显着降低（4.7 倍）乳腺肿瘤的发生率并增加 II 型胶原蛋白的表达，这可能有助于限制扩散。这些有希望的结果支持 ME 作为乳腺癌预防性治疗的潜在适用性。