Improvement of biodistribution with PEGylated liposomes containing docetaxel with degradable starch microspheres for hepatic arterial infusion in the treatment of liver metastases: a study in CC-531 liver tumor-bearing WAG RIJ rats.

AIM

To improve the drug concentration in liver metastases, docetaxel was encapsulated in polyethyleneglycol-liposomes and administered regionally with degradable starch microspheres (DSM).

MATERIALS AND METHODS

A rodent model of solitary metastasis (CC-531 adenocarcinoma) was studied. The animals were randomized into six groups and treated with 15 ng/kg docetaxel: I: intravenous (i.v.). II: PEG-liposomes i.v.; III: intraartial (i.a.) via the hepatica artery; IV: i.a.) + DSM; V: PEG-liposomes i.a.; and VI: PEG-liposomes i.a. + DSM. The docetaxel concentration in the serum, liver and liver tumor at defined times (5, 15, 30, 60,120 240 min and 24 h) was measured using HPLC.

RESULTS

The area under the concentration (AUC) versus time curves showed an 11-fold higher concentration in the tumor tissue when comparing the docetaxel-PEG-liposomes i.a. + DSM group to the i.v. group (p<0.01).

CONCLUSION

Compared to intravenous therapy, i.a. therapy with docetaxel-PEG-liposomes + DSM results in higher tumor tissue concentrations.