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A new approach for skin tumor treatment: from delivery system characterization to in vivo evaluation
Denize Ainbinder1, Elka Touitou
1Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, POB 12065, Jerusalem, 91120, Israel.
Abstract:
Topical therapy for skin cancer is considered ineffective, due to insufficient penetration of the anticancer drug into the tumor located in the deep layers of the skin. The aim of this work was to investigate a new system, Tumorep DS, tailored to deliver the anti-cancer actives into the tumor cells in the deep skin and to induce cell differentiation. Tumorep DS containing 5-fluorouracil (5-FU) anticancer drug and a sulfoxide derivative, as a differentiation agent, was characterized and tested for storage stability. The system was tested in cell lines, in vitro and in animal models. Experiments were carried out on five cell types: three tumorigenic (TE.354.T, ES-2, and Mel624), one precancerous (HaCaT), and a primary keratinocyte (human normal keratinocytes) cell culture. Treatment of keratinocytes with Tumorep DS resulted in reduction in the percent of keratin 14-positive cells, suggesting its ability to induce cell differentiation. Skin penetration was assessed in vitro in Franz diffusion cells and in vivo. The antitumor effect of the new system evaluated in two skin cancer animal models showed a significant repression of tumor development, which was significantly better statistically than a 5-FU commercial product. Tumorep DS was found to be safe to the skin when tested in vitro in the EpiDerm™ skin irritation test and in animals.
Insights
A novel topical delivery system, Tumorep DS, enhances anti-cancer drug penetration for deep skin tumors. This system demonstrated superior efficacy and safety compared to traditional treatments, offering new hope for skin cancer therapy.
Area of Science:
- Dermatology
- Oncology
- Nanotechnology
- Drug Delivery
Background:
- Topical skin cancer treatment faces challenges with drug penetration into deep skin layers.
- Developing effective delivery systems is crucial for enhancing therapeutic outcomes.
Purpose of the Study:
- To investigate Tumorep DS, a novel system designed for deep skin tumor targeting and cell differentiation.
- To evaluate the efficacy and safety of Tumorep DS containing 5-fluorouracil (5-FU) and a sulfoxide derivative.
Main Methods:
- Tumorep DS was characterized and tested for stability.
- In vitro studies involved five cell types, including tumorigenic, precancerous, and normal keratinocytes.
- In vivo experiments utilized skin cancer animal models and skin penetration assessments.
Main Results:
- Tumorep DS induced keratinocyte differentiation, indicated by reduced keratin 14-positive cells.
- Significant repression of tumor development was observed in animal models, outperforming a commercial 5-FU product.
- Tumorep DS demonstrated safety in skin irritation tests and animal studies.
Conclusions:
- Tumorep DS is a promising topical delivery system for skin cancer treatment.
- The system effectively delivers anti-cancer agents to deep skin tumors and induces cell differentiation.
- Tumorep DS offers a safer and more effective alternative to conventional topical therapies.
