Oridonin-loaded liposomes targeting lung cancer: formulation and delivery in vitro and in vivo.

PURPOSE: Oridonin (ORI) is an ent-kaurene tetracyclic diterpenoid with anti-tumor activities in various tumor cell lines. However, its hydrophobicity and non-targeting have greatly limited the clinical application of ORI. In the present study, long-circulating liposomes loading ORI and targeting lung cancer cells were established to solve these problems.

METHODS

1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene-glycol (DSPE-PEG), modified with a homing peptide with the sequence YSAYPDSVPMMSK (YSA), was employed to constitute the matrix of liposomes in combination with soybean lecithin and cholesterol. Meanwhile, the characterization, stability, in vitro release, and delivery in vitro and in vivo of the prepared liposomes were studied.

RESULTS

The results revealed that the prepared ORI-loaded liposomes exhibited a regular sphere with particle size of 140.64 ± 12.94 nm. The prepared liposomes showed good stability at 5 °C and sustained release profile in PBS solution. YSA modification to the liposomes enabled increased uptake by human lung cancer A549 cells, thereby increasing cytotoxicity on A549 cells. The pharmacokinetics study showed a higher area under the concentration time curve (AUC), a longer mean residence time (MRT), a slower plasma clearance (CL) and a prolonged half life time (t1/2) for ORI-loaded liposomes. Of important, the prepared liposomes exhibited a concentrated distribution in tumor tissues after intravenous injection. Therefore, ORI-loaded liposomes significantly inhibited tumor growth in tumor xenograft nude mice inoculated with A549 cells.

CONCLUSION

In conclusion, the constructed ORI-loaded liposomes might be a novel and promising delivery system for ORI in the treatment of lung cancer.