The objective of this study was to prepare cubosomal nanoparticles containing a hydrophilic anticancer drug 5-fluorouracil (5-FU) for liver targeting. Cubosomal dispersions were prepared by disrupting a cubic gel phase of monoolein and water in the presence of Poloxamer 407 as a stabilizer. Cubosomes loaded with 5-FU were characterized in vitro and in vivo. In vitro, 5-FU-loaded cubosomes entrapped 31.21% drug and revealed nanometer-sized particles with a narrow particle size distribution. In vitro 5-FU release from cubosomes exhibited a phase of rapid release of about half of the entrapped drug during the first hour, followed by a relatively slower drug release as compared to 5-FU solution. In vivo biodistribution experiments indicated that the cubosomal formulation significantly (P
Graphical abstract 5-Fluorouracil (5-FU) was successfully incorporated into cubosomal nanoparticles. Cubosomes loaded with 5-FU exhibited reasonable in vitro characteristics. Moreover, in vivo biodistribution of 5-FU in rat׳s liver indicated that the cubosomal formulation increased 5-FU liver concentration (nearly 5-fold) compared to 5-FU solution. In conclusion, cubosomes containing 5-FU has significant liver targeting properties.