In vitro and in vivo studies of lipid-based nanocarriers for oral N3-o-toluyl-fluorouracil delivery

Lipid-based drug delivery systems show great potential for enhancing oral bioavailability but have not been broadly applied, largely due to lack of general formulation guidance. In the previous studies, three different formulations including anionic SLNs, cationic SLNs, and liposomes were investigated and significantly enhanced the oral bioavailability of N-3-o-toluyl-fluorouracil (TFu) compared with its aqueous suspension, which indicated their high potential as oral delivery carriers. In order to define which formulation is worthy of being further researched and developed, the studies on Caco-2 cell model and rat intestine were investigated. In both studies of crossing Caco-2 cell monolayers and the single-pass intestinal perfusion (SPIP) in rat, SLNs exhibited much more capability to enhance transport of TFu than liposomes. More specifically, in cell study, the P-app values of cationic SLNs (p < 0.01) and anionic SLNs (p < 0.05) were significantly higher than liposomes. Especially the cationic SLNs present the most effective capacity. During SPIP study, both Ka and uptake percentage of these three different formulations followed a rank order: anionic SLN > cationic SLN > liposomes. In addition, the P-eff of different nanocarriers in various intestinal segments indicated they all exhibited site-dependent absorption behavior. By comparing the transmucosal behavior of these nanocarriers in vitro and in vivo, the anionic SLNs were identified to be more effective in the transport of TFu and were worthy of being further researched and developed.