Folate-targeted long-circulating 5-fluorouracil liposomes: preparation, characterization, anti-tumor effect and pharmacokinetic profile in rats

5-Fluorouracil (5-Fu) is a chemotherapy drug that can treat various cancers. However, its short plasma half-life and severe adverse reactions limit its wide application in clinical utility. To overcome these drawbacks, in this study, 5-Fu long-circulating liposomes (SSL-5-Fu Lip) were prepared by the film hydration method. DSPE-PEG₂₀₀₀-FA was conjugated to the surface of SSL-5-Fu Lip through amidation reaction, resulting in the successful preparation of FA-SSL-5-Fu Lip. The particle size and zeta potential were measured. The encapsulation efficiency of 5-Fu was determined by high-performance liquid chromatography (HPLC), and the drug loading was calculated. The stability of FA-SSL-5-Fu Lip was evaluated at 4 °C based on particle size and PDI. Pharmacokinetic studies were conducted in male Sprague-Dawley (SD) rats. The average particle size of the liposomes was 139.11 ± 3.1 nm, and the zeta potential was -4.30 ± 0.91 mV. The encapsulation efficiency and drug loading of 5-Fu were 76.88 ± 4.23% and 24.14 ± 0.97%, respectively. The half-lives of 5-Fu and FA-SSL-5-Fu Lip were 0.319 h and 1.059 h, respectively. It can be preliminarily proved that FA-SSL-5-Fu Lip has the effect of prolonging circulation time. Compared with free 5-Fu, it prolongs the circulation time of the drug in the body, laying a foundation for its clinical application.