An alternative hybrid lipid nanosystem combining cytotoxic and magnetic properties as a tool to potentiate antitumor effect of 5-fluorouracil.

ABSTRACT

AIMS: Colorectal cancer is the third most frequent type of cancer and the second leading cause of cancer-related deaths worldwide. The majority of cases are diagnosed at a later stage, leading to the need for more aggressive treatments such as chemotherapy. 5-Fluorouracil (5-FU), known for its high cytotoxic properties has emerged as a chemotherapeutic agent. However, it presents several drawbacks such as lack of specificity and short half-life. To reduce these drawbacks, several strategies have been designed namely chemical modification or association to drug delivery systems. MATERIALS AND METHODS: Current research was focused on the design, physicochemical characterization and in vitro evaluation of a lipid-based system loaded with 5-FU. Furthermore, aiming to maximize preferential targeting and release at tumour sites, a hybrid lipid-based system, combining both therapeutic and magnetic properties was developed and validated. For this purpose, liposomes co-loaded with 5-FU and iron oxide (II, III) nanoparticles were accomplished. KEY FINDINGS: The characterization of the developed nanoformulation was performed in terms of incorporation parameters, mean size and surface charge. In vitro studies assessed in a murine colon cancer cell line confirmed that 5-FU antiproliferative activity was preserved after incorporation in liposomes. In same model, iron oxide (II, III) nanoparticles did not exhibit cytotoxic properties. Additionally, the presence of these nanoparticles was shown to confer magnetic properties to the liposomes, allowing them to respond to external magnetic fields. SIGNIFICANCE: Overall, a lipid nanosystem loading a chemotherapeutic agent displaying magnetic characteristics was successfully designed and physicochemically characterized, for further in vivo applications.