Unlocking the Promise of Repurposed Clotrimazole for Skin Cancer Therapy Utilizing Nanosuspension - A Promising Anticancer Gel

Abstract

Skin cancer is one of the most commonly diagnosed cancers globally. Although melanoma is the deadliest form of skin cancer, non-melanoma skin cancers also contribute significantly to patients’ morbidity. Yet, current skin cancer treatments often have limitations, which raises an urgency to repurpose existing medications and utilize the most advanced new drug delivery systems, like nanotechnology, to boost effectiveness, reduce side effects, and break down barriers in cancer treatment. Clotrimazole is an antimycotic drug that has been used for years to treat fungal skin infections; moreover, recent studies have highlighted its potential benefits for skin cancer. However, its nanosuspension gel formulation for skin cancer has not been investigated. This study is the first to assess a nanosuspension gel containing clotrimazole for skin cancer in comparison to the commercially available clotrimazole cream, Candistan®. Soybean lecithin was used as a nano-based drug carrier within a Carbopol gel. The physicochemical properties of the nanocarrier and the gel were assessed and optimized. The optimized formulation was then tested in the skin cancer rat model. The results demonstrated a significant improvement in both histopathological and biochemical analyses compared to those of the commercial clotrimazole product. The clotrimazole nanosuspension gel effectively reduced skin inflammation and cell proliferation in rats, significantly lowering the levels of VEGF, NF-κB-p65, KI-67, and Sox 2. These findings provide strong evidence for the potential of clotrimazole nanosuspension gel as an effective innovative treatment for skin cancer due to its anti-inflammatory and anti-proliferative properties and improved bioavailability.