Since regional
drug administration enables to maintain a high
drug concentration within
tumors, we compared the plasma concentration and biodistribution of
doxorubicin (Dox) from
drug-loaded conventional
liposomes by local or systemic administration. The results demonstrated that
drug concentration was substantially improved in liver as well as a decrease in blood and other organs by spleen injection mimicking portal vein perfusion (regional administration). To further investigate the targeted
therapeutic effect of galactosylated
liposome encapsulated
doxorubicin (Dox) by regional administration, liver targeting
liposomes were prepared by incorporating galactosylated-
DPPE to conventional
liposomes.
Liposome uptake and targeting were verified in vitro and in vivo by fluorescence microscopy and xenogen IVIS imaging system, respectively. The results showed that
galactose targeted
liposomes presented a stronger specific cell uptake by human
hepatocellular carcinoma HepG2 cells compared to the non-targeted
liposomes. In vivo fluorescence imaging showed that the intra-hepatic deposition of conventional and galactosylated
liposomes via spleen injection was more than that via tail vein administration, and galactosylated
liposomes had higher fluorescent intensity over conventional
liposomes in the liver post spleen administration. The anti-
tumor effect of various
drug administration routes for both liposomal formulations was evaluated using a murine liver
metastasis model of
colon cancer. The results indicated that
tumor progression in the liver and mesenteric lymph nodes was significantly suppressed by Dox-loaded galactosylated
liposomes via spleen injection, while no significance was observed in non-targeted formulations. Our data indicated that local perfusion of galactosylated
liposomal doxorubicin had a great promise for the treatment of liver
metastasis from
colon cancer.