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A mucoadhesive patch loaded with freeze-dried liposomes for the local treatment of oral tumors

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Abstract

Oral cancers affect millions of people globally, with increasing incidences among adults aged 35 and above. Poor drug uptake by lesions in the oral cavity following systemic administration, as well as limited localized treatment modalities for oral tumors, result in poor patient quality of life and high mortality. Here, we describe a solid, dissolvable, bioadhesive alginate patch containing freeze-dried doxorubicin-loaded liposomes as a local treatment for oral tumors located on the tongue. By varying the alginate-to-liposome ratio in the mucoadhesive patch, we could control the degree of bioadhesion to the tongue and the release profile of the drug-loaded liposomes from the matrix. In vitro, exposing squamous cell carcinoma (SCC) to the alginate mucoadhesive patch or tablet resulted in dose-dependent cancer-cell death. In vivo, the efficacy of the local treatment was demonstrated in mice bearing orthotopic SCC tumors in the tongue. The bioadhesive patch, applied directly above the lesion, significantly reduced the tumor size and treatment-associated side effects compared to implanted patches or systemic drug administration. This study demonstrates that local bioadhesive therapies are effective in treating cancers of the oral cavity.

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Acknowledgements

The authors acknowledge the support of the Technion Integrated Cancer Center (TICC), the Russell Berrie Nanotechnology Institute (RBNI), and the Lorry I. Lokey Interdisciplinary Center for Life Sciences & Engineering. The authors wish to thank Dr. Naama Koifman for her help with cryo-SEM imaging. The authors would like to thank Ms. Natalie Page for proofreading of the article.

Funding

This project received funding from the Israel Ministry of Economy for a Kamin Grant (52752, 63379, 69230). A. Schroeder acknowledges the contribution of European Union’s Horizon 2020 research and innovation programme under grant agreement No 680242-ERC-[Next-Generation Personalized Diagnostic Nanotechnologies for Predicting Response to Cancer Medicine]; Israel Science Foundation (1778/13, 1421/17); Israel Ministry of Science and Technology (3–17418); Phospholipid Research Center Grant (ASC-2018–062/1–1); Leventhal 2020 COVID19 Research Fund (ATS #11947); Louis family Cancer Research Fund; a Mallat Family Foundation grant; The Unger Family Fund; Carrie Rosenblatt Cancer Research Fund; Alon and Taub Fellowships.

Supplementary data are available online, and from the corresponding author upon reasonable request.

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Author notes

  1. Layan Habib and Mohammed Alyan contributed equally to this work.

Authors and Affiliations

  1. The Inter-Departmental Program of Biotechnology, Technion - Israel Institute of Technology, Haifa, Israel

    Layan Habib & Mohammed Alyan

  2. The Louis Family Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Department of Chemical Engineering, Technion – Israel Institute of Technology, Haifa, Israel

    Mohammed Alyan, Jeny Shklover, Janna Shainsky & Avi Schroeder

  3. Department of Chemical Engineering, Technion – Israel Institute of Technology, Haifa, Israel

    Havazelet Bianco-Peled

  4. Department of Oral and Maxillofacial Surgery, Baruch Padeh Medical Center, Poriya, Israel

    Yasmine Ghantous & Imad Abu El-Naaj

  5. The Russell Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Haifa, Israel

    Havazelet Bianco-Peled

  6. Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel

    Imad Abu El-Naaj

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  1. Layan Habib
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Contributions

Material preparation, data collection, and data analysis were done by Layan Habib, Mohammed Alyan, and Yasmine Ghantous. All authors contributed to the study’s conception and design and read and approved the final manuscript.

Corresponding author

Correspondence to Avi Schroeder.

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Ethics approval and consent to participate

All animal experiments were approved by, and were in compliance with, the Technion ethics committee (Approval numbers IL-056–05-16, IL-098–08-20), and all national and institutional guidelines for the care and use of laboratory animals were followed. No human studies were carried out by the authors for this article.

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Competing interests

 Based on the research funding, a provisional patent application was submitted by Bianco-Peled H, Schroeder A, Abu El-Naaj I, Habib L, Alyan M and Ghantous Y.

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Habib, L., Alyan, M., Ghantous, Y. et al. A mucoadhesive patch loaded with freeze-dried liposomes for the local treatment of oral tumors. Drug Deliv. and Transl. Res. 13, 1228–1245 (2023). https://doi.org/10.1007/s13346-022-01224-4

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