Comparative pharmacokinetics and antitumor efficacy of doxorubicin encapsulated in soybean-derived sterols and poly(ethylene glycol) liposomes in mice

The blood clearance, tissue uptake and antitumor efficacy of doxorubicin (DOX) encapsulated in two different types of liposomes against hepatoma 22 (H22) and sarcoma 180 (S180) tumors were examined in mice. Liposomes were composed of dipalmitoylphosphatidylcholine (DPPC) and soybean-derived sterol mixture (SS) at a 7:4 molar ratio (DPPC/SS-liposomes), a new stabilizer like cholesterol, and 6 mol% distearoylphosphatidylethanolamine (DSPE) derivatized with poly(ethylene glycol) (PEG) (DPPC/SS/PEG-liposomes). Pharmacokinetic analysis of drug disposition was based on the areas under the curve (AUG) for liposome-encapsulated DOX uptake per gram tissue up to 24 h following i.v. injection. The highest tissue AUC values with both liposome types were obtained in spleen and liver. The serum AUC value of DPPC/SS/PEG-liposomes was 1.3 times higher than that of DPPC/SS-liposomes (P < 0.05). These findings indicate that the encapsulation of DOX in either DPPC/SS- or DPPC/SS/PEG-liposomes markedly prolonged the blood circulation time. The antitumor efficacy of DOX encapsulated in liposomes was compared with that of the free drug at two doses, 5 and 10 mg/kg. The antitumor efficacy of DOX encapsulated in DPPC/SS- and DPPC/SS/PEG-liposomes was different between the H22 and S180 tumor. DPPC/SS-liposomes were significantly more active against the H22 tumor than the free drug and the DPPC/SS/PEG-liposomes markedly more active (ILS: 32.1 and 97.7%, respectively, P < 0.001), reflecting ions circulation. The antitumor efficacy of the DPPC/SS/PEG-liposomes against S180 tumor-bearing mice was significantly high but that of DPPC/SS-liposomes was not, in comparison with free DOX. (C) 1997 Elsevier Science B.V.