Nanoemulsion-based transdermal delivery of third-generation steroidal and non-steroidal aromatase inhibitors in preclinical models.

Sep 30, 2024

Experts: Lanyang Gao,Lin Gao,Shiyao Huang,Lei Sun,Mei Li,Chen Shen,Youyou Chen,Ruihao Tan,Yuji Chen,Chengguo Zhan,Frank Heinrich Wieland,Yingying Liu,Yinan Zhang,Yao Luo

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.

Author

admin

View all posts

ABOUT THE EXPERTS

Lanyang Gao,Lin Gao,Shiyao Huang,Lei Sun,Mei Li,Chen Shen,Youyou Chen,Ruihao Tan,Yuji Chen,Chengguo Zhan,Frank Heinrich Wieland,Yingying Liu,Yinan Zhang,Yao Luo

Lanyang Gao

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.

Lin Gao

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.

Shiyao Huang

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.

Lei Sun

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.

Mei Li

Department of Laboratory Medicine/Sichuan Medical Laboratory Clinical Medicine Research Center, Innovation Institute for Integration of Medicine and Engineering, West China Hospital, Sichuan University, Chengdu, China.

Chen Shen

Department of Laboratory Medicine/Sichuan Medical Laboratory Clinical Medicine Research Center, Innovation Institute for Integration of Medicine and Engineering, West China Hospital, Sichuan University, Chengdu, China.

Youyou Chen

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.

Ruihao Tan

School of Chemical Science and Engineering, Tongji University, Shanghai, China.

Yuji Chen

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.

Chengguo Zhan

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.

Frank Heinrich Wieland

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.

Yingying Liu

School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine (Shanghai), Shanghai Jiao Tong University, Shanghai, China.

Yinan Zhang

School of Chemical Science and Engineering, Tongji University, Shanghai, China.

Yao Luo

Department of Laboratory Medicine/Sichuan Medical Laboratory Clinical Medicine Research Center, Innovation Institute for Integration of Medicine and Engineering, West China Hospital, Sichuan University, Chengdu, China.