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• W1963806424 abstract "Abstract Enhanced delivery of doxorubicin (DXR) to colon 26 in mice was studied by the long-circulating liposomes (LCL) composed of distearoylphosphatidylcholine cholesterol (DSPC CH) (1 1. m m) and 6 mol° distearoyl phosphatidyl ethanolamine (DSPE) derivatives of poly(ethylene glycol) (PEG) with an average molecular weight of 1000. LCL was approximately 100 nm in mean diameter and encapsulated DXR with > 98% entrapping efficiency by the transmembrane pH gradient method. The control liposomes (LP) which had the same lipid composition, similar size and DXR entrapment as LCL. but did not have amphipathic PEG. were used for comparison. Liposomal DXR and free DXR were injected intravenously at a dose of 5 mg DXR kg to Balb c mice implanted subcutaneously with colon 26 carcinoma. DXR encapsulated in LCL showed high blood levels up to 24 h after injection, compared with the corresponding DXR-LP and free DXR. The value of the area under the curve (AUC) of blood was approximately 2.4-or 810-fold higher than that of DXR-LP or free DXR. respectively. LCL decreased the uptake amount of DXR by the reticuloendothelial system (RES) of liver and spleen. Both liposomal formulations effectively reduced the DXR concentrations in heart compared with free DXR. Compared with DXR-LP or free drug. DXR-LCL produced an approximately 3.6-or 10.5-fold increased DXR level in tumor. respectively, at 6 h after injection. The AUC value of tumor tissue for DXR-LCL was 3.4-or 9.4-fold higher than that of DXR-LP or free DXR. respectively. These high tumor levels of DXR by LCL corresponded to the prolonged residence feature of liposomes. Therapeutic experiments were performed with three different formulations of DXR. Administration of DXR-LCL at a dose of 10 mg DXR kg resulted in effective retardation of tumor growth and 2-fold prolongation of survival times compared with DXR-LP. free drug and saline. Our results indicate that DXR encapsulated in long-circulating liposomes is significantly more active against colon 26 carcinoma than the conventional liposome (DSPC CH. 1:1. m m) formulation of DXR and free drug. Thus long-circulating liposomes should be useful carriers of chemotherapeutic agents for the treatment of solid tumor." @default.
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• W1963806424 date "1995-12-01" @default.
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• W1963806424 title "Enhanced tumor targeting and improved antitumor activity of doxorubicin by long-circulating liposomes containing amphipathic poly(ethylene glycol)" @default.
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• W1963806424 doi "https://doi.org/10.1016/0378-5173(95)04074-9" @default.
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