Cationic liposomes loaded with doxorubicin targeting to the tumor neovasculature in vitro

This study was conducted to investigate the in vitro characteristics of cationic liposomes composed of 3β-［N-［2-(N′,N′-dimethylamino)ethyl］ carbamoyl］ cholesterol (DC-Chol) and dipalmitoylphosphatidylcholine loaded with doxorubicin (DXR), and to provide useful information for the in vivo tumor vascular targeting of cationic liposomes. Cationic liposomes composed of different amounts of DC-Chol (0 mol%, 10 mol%, 25 mol%, 50 mol%) were loaded with the conventional anti-cancer drug doxorubicin. Their size, zeta potential, encapsulation efficiency, and DXR release in vitro were investigated. Moreover, their uptake by rat aortic endothelial cells (RAECs) was observed at 15 min, 30 min, 1 h, and 4 h of incubation. FITC-Dextran was iv injected to the H22 tumor-bearing KM mice to stain the neovasculature. The characteristics of resulting DXR-loaded cationic liposomes were in stable characteristics with particle sizes around 100-200 nm and capsulation efficiency greater than 90%. Increased cationic lipid led to enhanced zeta potential, and meanwhile it also resulted in quick release of the loaded drug, indicating increased slits or pores on the membrane upon the addition of DC-Chol. RAECs could more avidly take up DXR-loaded cationic liposomes when the content of DC-Chol increased in the liposomes, and DXR were quickly released in the cytoplasm and transported to the nuclei. The neovasculature stained by FITC-Dextran was clearly observed. DXR-cationic liposomes composed of DC-Chol could be used for tumor vascular targeting in vivo for further study.