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 doxorubic in (DOX) encapsulated in two different types of liposomes against hepa toma 22 (H22) and sarcoma 180 (S180) tumors were examined in mice. Lip osomes were composed of dipalmitoylphosphatidylcholine (DPPC) and soyb ean-derived sterol mixture (SS) at a 7:4 molar ratio (DPPC/SS-liposome s), a new stabilizer like cholesterol, and 6 mol% distearoylphosphatid ylethanolamine (DSPE) derivatized with poly(ethylene glycol) (PEG) (DP PC/SS/PEG-liposomes). Pharmacokinetic analysis of drug disposition was based on the areas under the curve (AUG) for liposome-encapsulated DO X uptake per gram tissue up to 24 h following i.v. injection. The high est 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 indi cate that the encapsulation of DOX in either DPPC/SS- or DPPC/SS/PEG-l iposomes markedly prolonged the blood circulation time. The antitumor efficacy of DOX encapsulated in liposomes was compared with that of th e free drug at two doses, 5 and 10 mg/kg. The antitumor efficacy of DO X encapsulated in DPPC/SS- and DPPC/SS/PEG-liposomes was different bet ween 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-l iposomes markedly more active (ILS: 32.1 and 97.7%, respectively, P < 0.001), reflecting ions circulation. The antitumor efficacy of the DPP C/SS/PEG-liposomes against S180 tumor-bearing mice was significantly h igh but that of DPPC/SS-liposomes was not, in comparison with free DOX . (C) 1997 Elsevier Science B.V.