Local drug delivery system for the treatment of tongue squamous cell carcinoma in rats

Kakabadze,Mariam Z.; Paresishvili,Teona; Mardaleishvili,Konstantine; Vadachkoria,Zurab; Kipshidze,Nicholas; Jangavadze,Mikheil; Karalashvili,Lia; Ghambashidze,Ketevan; Chakhunashvili,David; Kakabadze,Zurab

doi:10.3892/ol.2021.13131

Local drug delivery system for the treatment of tongue squamous cell carcinoma in rats

Authors:
- Mariam Z. Kakabadze
- Teona Paresishvili
- Konstantine Mardaleishvili
- Zurab Vadachkoria
- Nicholas Kipshidze
- Mikheil Jangavadze
- Lia Karalashvili
- Ketevan Ghambashidze
- David Chakhunashvili
- Zurab Kakabadze
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Affiliations: Department of Clinical Anatomy and Operative Surgery, Iv. Javakhishvili Tbilisi State University, 0179 Tbilisi, Georgia, Department of Clinical Anatomy, Tbilisi State Medical University, 0186 Tbilisi, Georgia, Department of Head and Neck Surgery, Mardaleishvili Medical Center, 0179 Tbilisi, Georgia, Department of Child and Adolescent Maxillo‑facial Surgery and Surgical Stomatology, Tbilisi State Medical University, 0186 Tbilisi, Georgia, Department of Interventional Cardiology, Cardiovascular Research Foundation, New York, NY 10019, USA
Published online on: November 11, 2021 https://doi.org/10.3892/ol.2021.13131
Article Number: 13
Copyright: © Kakabadze et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study describes a local drug delivery system with two functions, which can suppress tumor growth and accelerate wound healing. Thе system consists of a two‑layer multicomponent fibrin‑based gel (MCPFTG). The internal layer of MCPFTG, which is in direct contact with the wound surface, contains cisplatin placed on a CultiSpher‑S collagen microcarrier. The external layer of MCPFTG consists of a CultiSpher‑S microcarrier with lyophilized bone marrow stem cells (BMSCs). The efficacy of MCPFTG was evaluated in a rat model of squamous cell carcinoma of the tongue created with 4‑nitroquinoline 1‑oxide. The results of the study showed that, within 20‑25 days, a non‑healing wound of the tongue was formed in animals that underwent only 85% resection of squamous cell carcinoma, while rapid progression of the residual tumor was concomitantly observed. Immunohistochemical methods revealed high expression of cyclin D1 and low expression of E‑cadherin in these animals. Additionally, high expression of p63 and Ki‑67 was noted. In 80% of animals with squamous cell carcinoma of the tongue that were treated with MCPFTG after 85% tumor resection, a noticeable suppression of tumor growth was evident throughout 150 days, and tumor recurrence was not detected. Immunohistochemistry revealed low or moderate expression of cyclin D1, and high expression of E‑cadherin throughout the whole observation period. The MCPFTG‑based local drug delivery system was shown to be effective in suppressing tumor growth and preventing recurrence. MCPFTG decreased the toxicity of cisplatin and enhanced its antitumor activity. In addition, lyophilized paracrine BMSC factors present in MCPFTG accelerated wound healing after tumor removal. Thus, the present study suggests novel opportunities for the development of a multifunctional drug delivery system for the treatment of squamous cell carcinoma.

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