Zhang, X.; Hu, X.; Xie, Y.; Xie, L.; Chen, X.; Peng, M.; Li, D.; Deng, J.; Xiao, D.; Yang, X. Metformin-Loaded Chitosan Hydrogels Suppress Bladder Tumor Growth in an Orthotopic Mouse Model via Intravesical Administration. Molecules2023, 28, 6720.
Zhang, X.; Hu, X.; Xie, Y.; Xie, L.; Chen, X.; Peng, M.; Li, D.; Deng, J.; Xiao, D.; Yang, X. Metformin-Loaded Chitosan Hydrogels Suppress Bladder Tumor Growth in an Orthotopic Mouse Model via Intravesical Administration. Molecules 2023, 28, 6720.
Zhang, X.; Hu, X.; Xie, Y.; Xie, L.; Chen, X.; Peng, M.; Li, D.; Deng, J.; Xiao, D.; Yang, X. Metformin-Loaded Chitosan Hydrogels Suppress Bladder Tumor Growth in an Orthotopic Mouse Model via Intravesical Administration. Molecules2023, 28, 6720.
Zhang, X.; Hu, X.; Xie, Y.; Xie, L.; Chen, X.; Peng, M.; Li, D.; Deng, J.; Xiao, D.; Yang, X. Metformin-Loaded Chitosan Hydrogels Suppress Bladder Tumor Growth in an Orthotopic Mouse Model via Intravesical Administration. Molecules 2023, 28, 6720.
Abstract
Our previous study found that intravesical perfusion metformin has excellent inhibitory effects against bladder cancer (BC). However, this administration route allows the drug to be diluted and excreted in urine. Therefore, increasing the adhesion of metformin to the bladder mucosal layer may prolong the retention time and increase the pharmacological activity. It is well known that chitosan (Cs) has a strong adhesion to the bladder mucosal layer. Thus, this study established a novel for-mulation of metformin to enhance its antitumor activity by extending its retention time. In this research, we prepared Cs freeze-dried powder and investigated the effect of metformin-loaded chitosan hydrogels (MLCH) in vitro and in vivo. The results showed that MLCH had a strong in-hibitory effect against proliferation and colony formation in vitro. The reduction in BC weight and expression of tumour biomarkers in orthotopic mice showed the robust antitumor activity of MLCH via intravesical administration in vivo. The non-toxic profile of MLCH was observed as well, using histological examinations. Mechanistically, MLCH showed stronger functional activation of the AMPK/mTOR signalling pathway compared with metformin alone. These findings highlighted the potential of this novel formulation as an efficient candidate for managing BC via intravesical ad-ministration.
Keywords
chitosan hydrogels; bladder cancer; metformin; intravesical administration; orthotopic model
Subject
Biology and Life Sciences, Other
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
