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.). PEG-liposomes i.v.; 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 mm 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.