芳香酶抑制剂可有效治疗激素受体阳性乳腺癌，尤其是绝经后女性。然而，口服给药的溶出不一致、吸收变化和副作用的挑战仍然存在。为了解决这些问题，透皮给药已成为一种可行的替代方案。在我们的研究中，我们开发了含有第三代芳香酶抑制剂依西美坦（EXE）或来曲唑（LE）的纳米乳透皮乳膏，并使用巴马小型猪、DMBA诱导乳腺等临床前模型评估了它们的毒性、抗肿瘤作用和雄激素效力。癌症大鼠和睾丸切除的雄性大鼠。我们的研究结果意义重大，表明这两种乳霜都能有效渗透皮肤，显示出令人印象深刻的抗乳腺癌效果。重要的是，EXE 霜在测试剂量下没有器官毒性，为其使用提供了令人放心的安全性。相比之下，LE乳膏在给定剂量下对动物表现出药物分子本身的可逆毒性，在停药和恢复3周后消失。该研究为第三代芳香酶抑制剂的临床安全使用奠定了坚实的基础。它强调了透皮乳膏作为一种有前景的给药载体。© 2024 作者。北京干细胞与再生医学研究院和John Wiley联合出版的《细胞增殖》

Aromatase inhibitors are effective in treating hormone receptor-positive breast cancer, particularly in postmenopausal women. However, the challenges of inconsistent dissolution, variable absorption and side effects with oral administration persist. To address these issues, transdermal delivery has emerged as a viable alternative. In our study, we have developed nanoemulsion-based transdermal creams containing third-generation aromatase inhibitors Exemestane (EXE) or Letrozole (LE) and evaluated their toxicity, anti-tumour effects and androgenic potency using preclinical models including Bama minipigs, DMBA-induced breast cancer rats and orchidectomized male rats. The results of our study are significant, suggesting that both creams effectively penetrated the skin, demonstrating an impressive anti-breast cancer effect. Importantly, EXE cream had no organ toxicity at the tested dose, providing a reassuring safety profile for its use. In contrast, LE cream displayed reversible toxicity from drug molecule itself in animals at the given dose, dissipating after 3 weeks of withdrawal and recovery. This study establishes a solid foundation for the safe clinical use of third-generation aromatase inhibitors. It highlights transdermal creams as a promising drug delivery carrier for administering them.© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.