Local Drug Delivery System for the Treatment of Tongue Squamous Cell Carcinoma

Abstract

Background. The global incidence of oral cancer is >300,000 cases, annually resulting in 145,400 cancer-associated deaths. The most widespread malignant tumor of the mouth is squamous cell carcinoma. It occurs in 80-90 % of all oral cancer cases. The treatment of oral squamous cell carcinoma includes surgery, chemotherapy, radiation therapy, and immunotherapy. Surgical resection is a key treatment method for tumors of the oral cavity and oropharynx. However, after tumor resection, the presence of residual tumor cells is frequent, which usually leads to tumor recurrence. Aim.   The aim of this study was to develop a targeted drug delivery system with two functions, which can suppress tumor growth and accelerate wound healing. Material and Methods. The system consists of a two-layer multicomponent fibrin-based gel (MCPFTG). The internal layer of MCPFTG, which comes in direct contact with the wound surface, contains cisplatin that is 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. Results. 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. Conclusion. The local drug delivery systems are promising method of treatment of squamous cell carcinoma. Our system reduces the toxicity of cisplatin and improves its antitumor activity. Thus, the present study suggests novel opportunities for the development of a drug delivery system for the treatment of squamous cell carcinoma.