Gao Lanyang, Gao Lin, Huang Shiyao, Sun Lei, Li Mei, Shen Chen, Chen Youyou, Tan Ruihao, Chen Yuji, Zhan Chengguo, Wieland Frank Heinrich, Liu Yingying, Zhang Yinan, Luo Yao
Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, Academician (Expert) Workstation of Sichuan Province, Department of General Surgery (Hepatopancreatobiliary Surgery), Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou, The Affiliated Hospital Southwest Medical University, Luzhou, China.
School of Chemical Science and Engineering, Tongji University, Shanghai, China.
Cell Prolif. 2025 Mar;58(3):e13753. doi: 10.1111/cpr.13753. Epub 2024 Sep 29.
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.
芳香酶抑制剂在治疗激素受体阳性乳腺癌方面有效，尤其是在绝经后女性中。然而，口服给药存在溶出不一致、吸收可变和副作用等挑战。为了解决这些问题，经皮给药已成为一种可行的替代方法。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）的纳米乳液基透皮乳膏，并使用巴马小型猪、二甲基苯并蒽诱导的乳腺癌大鼠和去势雄性大鼠等临床前模型评估了它们的毒性、抗肿瘤作用和雄激素活性。我们的研究结果意义重大，表明两种乳膏均能有效穿透皮肤，显示出令人印象深刻的抗乳腺癌效果。重要的是，EXE乳膏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乳膏在给定剂量下在动物中显示出药物分子本身的可逆毒性，停药和恢复3周后消失。这项研究为第三代芳香酶抑制剂的安全临床应用奠定了坚实基础。它突出了透皮乳膏作为给药的一种有前途的药物递送载体。
