Advancements in 5-Fluorouracil-Loaded Liposomal Nanosystems: A Comprehensive Review on Recent Innovations in Nanomedicine for Cancer Therapy

The increasing worldwide cancer prevalence is a result of population aging and expansion and changes in individuals' exposure to risk factors, many of which are linked to socioeconomic progress. 5-Fluorouracil (5-FU) is a primary chemotherapeutic drug used to treat several types of cancer. However, due to the limitations of 5-FU such as rapid metabolism, a short half-life, and limited membrane permeability, a high dosage of 5-FU is needed to reach the appropriate plasma concentration for strong anti-cancer activities, resulting in severe side effects and toxicities. Notably, during the cellular uptake by the tumor, hepatocytes, or other normal cells, the conversion of 5-FU to dihydro fluorouracil (DHFU) by the enzyme dihydropyrimidine dehydrogenase (DPD) is the step that limits the rate of 5-FU breakdown. Furthermore, approximately 80% of the given 5-FU is metabolized by DPD in the liver, thus nanoparticulate drug delivery system such as liposomes could prevent the excessive metabolism of 5-FU in liver, and with efficient tumor targeting properties is desired to lower the unwanted side effects and enhance the anticancer potency of the former. Therefore, the use of nanocarriers to address these issues and improve their therapeutic efficacy is strongly sought after. Liposomes are often used by researchers as nanocarriers to transport 5-FU because of their biocompatibility, drug loading capacity, longer circulation period, and improved permeability. The present review discusses on 5-FU-loaded liposomes, and the importance of former in delivering the desired concentration of drug, particularly to the tumors.