Loss of integrity of doxorubicin liposomes during transcellular transportation evidenced by fluorescence resonance energy transfer effect.

The aim of this work was to elucidate the influence of liposome characteristics on the transcellular process by in vitro studies that would enable designing more efficient oral formulations. Various liposomes with different properties were prepared, including 100-500 nm, anionic, cationic and PEGylated liposomes. All liposomes were labeled by fluorescence resonance energy transfer (FRET) probes to evaluate their integrity in cellular uptake and transport. The FRET fluorescent intensity is proportional to the amount of intact liposomes, which was used to calculate the amount of intact liposomes in cellular uptake and transport. The liposomal structures were found to lose their integrity during or after uptake and only about 20% intact liposomes were detected in cells. However, more cationic liposomes were transported integrally across cell monolayer and accounted for 40.49% of total transport by triple culture models of Caco-2/HT29-MTX/Raji B. These results suggest that liposomes could improve cellular uptake and transport of the payloads significantly, but only a small fraction of liposomes are transported integrally across epithelial monolayer. The study is therefore helpful to rationally fabricate more efficient oral liposomes for poorly water-soluble drugs or biomacromolecules.