5-Fluorouracil, innovative drug delivery systems to enhance bioavailability for topical use

5-Fluorouracil (5-FU) is a well-known chemotherapy drug, used for over 70 years in the treatment of several types of cancer. Topically, 5-FU has shown potential effect to treat premalignant and malignant lesions. However, the efficiency of topical 5-FU administration is limited to treat superficial pre-carcinogenic lesions. In this review we present the main characteristics of 5-FU, including its mechanism of action, dissolution, and bioavailability. Moreover, we highlight the delivery systems under development that include 5-FU carriers in topical treatments. Microemulsions and nanocarriers have demonstrated significant impact on the bioavailability of 5-FU in vitro and in vivo, increasing the drug effects on deeper layers of the skin, which has shown promising results in the treatment of precancerous and cancerous lesions. According to authors of clinical pilot studies, 5-FU occlusive dressing, 5-FU chemowrap, 5-FU transdermal, and their combination, resulting in a triple therapy, are more effective compared with cream formulation to treat precancer widespread in a skin area. Conclusion: Thus, by this review, we demonstrate that the delivery system under consideration greatly impacts 5-FU effects on the skin. [Display omitted] •Nanocarriers and microemulsions have shown high affinity for skin, promoting targetable delivery of 5-FU for topical use.•Chemowrap and combination therapy are innovative approaches for improving the healing outcome in precancerous skin.•Smart chemowrap using biosensors and pH-sensitive biomaterial can increase the cure rate of widespread skin precancer.