Antitumor Activity of Doxorubicin Encapsulated in Poly (ethylene glycol)-Coated Liposomes
The antitumor activity of doxorubicin (DXR) which had been encapsulated in poly (ethylene glycol) (PEG)-coated long-circulating liposomes was examined in mice inoculated with colon 26 carcinoma cells. Six mol% of the distearoylphosphatidylethanolamine derivative of PEGs with different molecular weig...
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| Published in | Biological & pharmaceutical bulletin Vol. 18; no. 9; pp. 1234 - 1237 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Tokyo
The Pharmaceutical Society of Japan
1995
Maruzen Japan Science and Technology Agency |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0918-6158 1347-5215 |
| DOI | 10.1248/bpb.18.1234 |
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| Abstract | The antitumor activity of doxorubicin (DXR) which had been encapsulated in poly (ethylene glycol) (PEG)-coated long-circulating liposomes was examined in mice inoculated with colon 26 carcinoma cells. Six mol% of the distearoylphosphatidylethanolamine derivative of PEGs with different molecular weights was incorporated in liposomes (90-110nm, mean diameter) composed of distearoylphosphatidylcholine/cholesterol (1/1, molar ratio), and the encapsulating efficiency of DXR in liposomes was more than 98% by the pH gradient method. Each concentration of DXR in blood and tumor tissue was significantly greater after administration of the drug encapsulated in PEG-coated liposomes (DXR-PEG-liposome) compared to the non-coated control liposomes or non-encapsulated free drug. DXR-PEG-liposome prepared with PEG1000 (DXR-PEG1000-liposome) more effectively increased the level of DXR in blood and tumor than did the preparations with PEG5000 or PEG12000. A single treatment with DXR-PEG1000-liposome (10mg DXR/kg) resulted in increased survival time. Further therapeutic improvement in terms of tumor growth retardation and prolongation of survival time were observed following multiple treatments with DXR-PEG1000-liposome (3×5mg DXR/kg). Long-circulating liposome coating optimized PEGs should be useful for the delivery of chemotherapeutic agents for the treatment of solid tumors. |
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| AbstractList | The antitumor activity of doxorubicin (DXR) which had been encapsulated in poly (ethylene glycol) (PEG)-coated long-circulating liposomes was examined in mice inoculated with colon 26 carcinoma cells. Six mol% of the distearoylphosphatidylethanolamine derivative of PEGs with different molecular weights was incorporated in liposomes (90-110nm, mean diameter) composed of distearoylphosphatidylcholine/cholesterol (1/1, molar ratio), and the encapsulating efficiency of DXR in liposomes was more than 98% by the pH gradient method. Each concentration of DXR in blood and tumor tissue was significantly greater after administration of the drug encapsulated in PEG-coated liposomes (DXR-PEG-liposome) compared to the non-coated control liposomes or non-encapsulated free drug. DXR-PEG-liposome prepared with PEG1000 (DXR-PEG1000-liposome) more effectively increased the level of DXR in blood and tumor than did the preparations with PEG5000 or PEG12000. A single treatment with DXR-PEG1000-liposome (10mg DXR/kg) resulted in increased survival time. Further therapeutic improvement in terms of tumor growth retardation and prolongation of survival time were observed following multiple treatments with DXR-PEG1000-liposome (3×5mg DXR/kg). Long-circulating liposome coating optimized PEGs should be useful for the delivery of chemotherapeutic agents for the treatment of solid tumors. The antitumor activity of doxorubicin (DXR) which had been encapsulated in poly(ethylene glycol) (PEP)-coated long-circulating liposomes was examined in mice inoculated with colon 26 carcinoma cells. Six mol% of the distearoylphosphatidylethanolamine derivative of PEGs with different molecular weights was incorporated in liposomes (90-110 nm, mean diameter) composed of distearoylphosphatidylcholine/cholesterol (1/1, molar ratio), and the encapsulating efficiency of DXR in liposomes was more than 98% by the pH gradient method. Each concentration of DXR in blood and tumor tissue was significantly greater after administration of the drug encapsulated in PEG-coated liposomes (DXR-PEG-liposome) compared to the non-coated control liposomes or non-encapsulated free drug. DXR-PEG-liposome prepared with PEG1000 (DXR-PEG1000-liposome) more effectively increased the level of DXR in blood and tumor than did the preparations with PEG5000 or PEG 12000. A single treatment with DXR-PEG1000-liposome (10 mg DXR/kg) resulted in increased survival time. Further therapeutic improvement in terms of tumor growth retardation and prolongation of survival time were observed following multiple treatments with DXR-PEG1000-liposome (3 x 5 mg DXR/kg). Long-circulating liposome coating optimized PEGs should be useful for the delivery of chemotherapeutic agents for the treatment of solid tumors. The antitumor activity of doxorubicin (DXR) which had been encapsulated in poly(ethylene glycol) (PEP)-coated long-circulating liposomes was examined in mice inoculated with colon 26 carcinoma cells. Six mol% of the distearoylphosphatidylethanolamine derivative of PEGs with different molecular weights was incorporated in liposomes (90-110 nm, mean diameter) composed of distearoylphosphatidylcholine/cholesterol (1/1, molar ratio), and the encapsulating efficiency of DXR in liposomes was more than 98% by the pH gradient method. Each concentration of DXR in blood and tumor tissue was significantly greater after administration of the drug encapsulated in PEG-coated liposomes (DXR-PEG-liposome) compared to the non-coated control liposomes or non-encapsulated free drug. DXR-PEG-liposome prepared with PEG1000 (DXR-PEG1000-liposome) more effectively increased the level of DXR in blood and tumor than did the preparations with PEG5000 or PEG 12000. A single treatment with DXR-PEG1000-liposome (10 mg DXR/kg) resulted in increased survival time. Further therapeutic improvement in terms of tumor growth retardation and prolongation of survival time were observed following multiple treatments with DXR-PEG1000-liposome (3 x 5 mg DXR/kg). Long-circulating liposome coating optimized PEGs should be useful for the delivery of chemotherapeutic agents for the treatment of solid tumors.The antitumor activity of doxorubicin (DXR) which had been encapsulated in poly(ethylene glycol) (PEP)-coated long-circulating liposomes was examined in mice inoculated with colon 26 carcinoma cells. Six mol% of the distearoylphosphatidylethanolamine derivative of PEGs with different molecular weights was incorporated in liposomes (90-110 nm, mean diameter) composed of distearoylphosphatidylcholine/cholesterol (1/1, molar ratio), and the encapsulating efficiency of DXR in liposomes was more than 98% by the pH gradient method. Each concentration of DXR in blood and tumor tissue was significantly greater after administration of the drug encapsulated in PEG-coated liposomes (DXR-PEG-liposome) compared to the non-coated control liposomes or non-encapsulated free drug. DXR-PEG-liposome prepared with PEG1000 (DXR-PEG1000-liposome) more effectively increased the level of DXR in blood and tumor than did the preparations with PEG5000 or PEG 12000. A single treatment with DXR-PEG1000-liposome (10 mg DXR/kg) resulted in increased survival time. Further therapeutic improvement in terms of tumor growth retardation and prolongation of survival time were observed following multiple treatments with DXR-PEG1000-liposome (3 x 5 mg DXR/kg). Long-circulating liposome coating optimized PEGs should be useful for the delivery of chemotherapeutic agents for the treatment of solid tumors. |
| Author | UNEZAKI, Sakae TSUCHIYA, Seishi IWATSURU, Motoharu HOSODA, Junichi MARUYAMA, Kazuo |
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| References | 10) Blume G., Cevec G., Biochim. Biophys. Acta, 1029, 91 (1990). 2) Mayhew E., Rustum Y., Vail W.J., Cancer Drug Deliv., 1, 43 (1983). 8) Gabizon A., Price D.C., Huberty J., Bresalier R.S., Papahadjopoulos D., Cancer Res., 50, 6371 (1990). 22) Gabizon A., Cancer Res., 52, 891 (1992). 14) Unezaki S., Maruyama K., Ishida O., Takahashi N., Iwatsuru M., J. Drug Target., 1, 287 (1993). 20) Woodle M.C., Lasic D.D., Biochim. Biophys. Acta, 1113, 171 (1992). 24) Maruyama K., Unezaki S., Takahashi N., Iwatsuru M., Biochim. Biophys. Acta, 1149, 209 (1993). 1) Olson F., Mayhew E., Maslow D., Rustum Y., Szoka F., Eur. J. Cancer Clin. Oncol., 18, 167 (1982). 25) Unezaki S., Maruyama K., Takahashi N., Koyama M., Yuda T., Suginaka A., Iwatsuru M., Pharm. Res., 11, 1180 (1994). 21) Mayhew E., Lasic D., Babbar S., Martin F.J., Int. J. Cancer, 51, 302 (1992). 5) Allen T.M., Chonn A., FEBS Lett., 223, 42 (1987). 6) Allen T.M., Hansen C., Rutledge J., Biochim. Biophys. Acta, 981, 27 (1989). 19) Vaage J., Mayhew E., Lasic D., Martin F., Int. J. Cancer, 51, 942 (1992). 13) Maruyama K., Yuda T., Okamoto A., Kojima S., Suginaka A., Iwatsuru M., Biochim. Biophys. Acta, 1128, 44 (1992). 17) Mayer L.D., Bally M.B., Cullis P.R., Biochim. Biophys. Acta, 857, 123 (1986). 18) Masuike J., Odake J., Kohagura M., Noda T., Takemoto T., Yakugaku Zasshi, 104, 620 (1984). 11) Klibanov A.L., Maruyama K., Beckerleg A.M., Torchilin V.P., Huang L., Biochim. Biophys. Acta, 1062, 142 (1991). 4) Gabizon A., Meshorer A., Barenholz Y., J. Nat. Cancer Inst., 77, 459 (1986). 15) Papahadjopoulos D., Allen T.M., Gabizon A., Mayhew E., Matthay K., Huang S.K., Lee K.D., Woodle M.C., Lasic D.D., Redemann C., Martin F.J., Proc. Natl. Acad. Sci. U.S.A., 88, 11460 (1991). 26) Senior J., Delgado C., Fisher D., Tilcock C., Gregoriadis G., Biochim. Biophys. Acta, 1062, 77 (1991). 12) Allen T.M., Hansen C., Martin F., Redemann C., Young A.Y., Biochim. Biophys. Acta, 1066, 29 (1991). 9) Klivanov A.L., Maruyama K., Torchilin V.P., Huang L., FEBS Lett., 268, 235 (1990). 16) Szoka F., Papahadjopoulos D., Proc. Natl. Acad. Sci. U.S.A., 75, 4149 (1978). 23) Vaage J., Donovan D., Mayhew E., Uster P., Woodle M., Int. J. Cancer, 54, 959 (1993). 7) Gabizon A., Papahadjopoulos D., Proc. Natl. Acad. Sci. U.S.A., 85, 6949 (1988). 27) Mori A., Klivanov A.L., Torchilin V.P., Huang L., FEBS Lett., 284, 263 (1991). 3) Gabizon A., Goren D., Fuks Z., Meshorer A., Barenholz Y., Br. J. Cancer, 51, 681 (1985). |
| References_xml | – reference: 8) Gabizon A., Price D.C., Huberty J., Bresalier R.S., Papahadjopoulos D., Cancer Res., 50, 6371 (1990). – reference: 1) Olson F., Mayhew E., Maslow D., Rustum Y., Szoka F., Eur. J. Cancer Clin. Oncol., 18, 167 (1982). – reference: 18) Masuike J., Odake J., Kohagura M., Noda T., Takemoto T., Yakugaku Zasshi, 104, 620 (1984). – reference: 24) Maruyama K., Unezaki S., Takahashi N., Iwatsuru M., Biochim. Biophys. Acta, 1149, 209 (1993). – reference: 17) Mayer L.D., Bally M.B., Cullis P.R., Biochim. Biophys. Acta, 857, 123 (1986). – reference: 11) Klibanov A.L., Maruyama K., Beckerleg A.M., Torchilin V.P., Huang L., Biochim. Biophys. Acta, 1062, 142 (1991). – reference: 22) Gabizon A., Cancer Res., 52, 891 (1992). – reference: 7) Gabizon A., Papahadjopoulos D., Proc. Natl. Acad. Sci. U.S.A., 85, 6949 (1988). – reference: 9) Klivanov A.L., Maruyama K., Torchilin V.P., Huang L., FEBS Lett., 268, 235 (1990). – reference: 10) Blume G., Cevec G., Biochim. Biophys. Acta, 1029, 91 (1990). – reference: 25) Unezaki S., Maruyama K., Takahashi N., Koyama M., Yuda T., Suginaka A., Iwatsuru M., Pharm. Res., 11, 1180 (1994). – reference: 4) Gabizon A., Meshorer A., Barenholz Y., J. Nat. Cancer Inst., 77, 459 (1986). – reference: 14) Unezaki S., Maruyama K., Ishida O., Takahashi N., Iwatsuru M., J. Drug Target., 1, 287 (1993). – reference: 16) Szoka F., Papahadjopoulos D., Proc. Natl. Acad. Sci. U.S.A., 75, 4149 (1978). – reference: 2) Mayhew E., Rustum Y., Vail W.J., Cancer Drug Deliv., 1, 43 (1983). – reference: 6) Allen T.M., Hansen C., Rutledge J., Biochim. Biophys. Acta, 981, 27 (1989). – reference: 23) Vaage J., Donovan D., Mayhew E., Uster P., Woodle M., Int. J. Cancer, 54, 959 (1993). – reference: 20) Woodle M.C., Lasic D.D., Biochim. Biophys. Acta, 1113, 171 (1992). – reference: 5) Allen T.M., Chonn A., FEBS Lett., 223, 42 (1987). – reference: 15) Papahadjopoulos D., Allen T.M., Gabizon A., Mayhew E., Matthay K., Huang S.K., Lee K.D., Woodle M.C., Lasic D.D., Redemann C., Martin F.J., Proc. Natl. Acad. Sci. U.S.A., 88, 11460 (1991). – reference: 26) Senior J., Delgado C., Fisher D., Tilcock C., Gregoriadis G., Biochim. Biophys. Acta, 1062, 77 (1991). – reference: 27) Mori A., Klivanov A.L., Torchilin V.P., Huang L., FEBS Lett., 284, 263 (1991). – reference: 12) Allen T.M., Hansen C., Martin F., Redemann C., Young A.Y., Biochim. Biophys. Acta, 1066, 29 (1991). – reference: 13) Maruyama K., Yuda T., Okamoto A., Kojima S., Suginaka A., Iwatsuru M., Biochim. Biophys. Acta, 1128, 44 (1992). – reference: 19) Vaage J., Mayhew E., Lasic D., Martin F., Int. J. Cancer, 51, 942 (1992). – reference: 3) Gabizon A., Goren D., Fuks Z., Meshorer A., Barenholz Y., Br. J. Cancer, 51, 681 (1985). – reference: 21) Mayhew E., Lasic D., Babbar S., Martin F.J., Int. J. Cancer, 51, 302 (1992). |
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| Snippet | The antitumor activity of doxorubicin (DXR) which had been encapsulated in poly (ethylene glycol) (PEG)-coated long-circulating liposomes was examined in mice... The antitumor activity of doxorubicin (DXR) which had been encapsulated in poly(ethylene glycol) (PEP)-coated long-circulating liposomes was examined in mice... |
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| SubjectTerms | Animals Antibiotics, Antineoplastic - administration & dosage Antineoplastic agents Biological and medical sciences Chemotherapy doxorubicin Doxorubicin - administration & dosage Doxorubicin - pharmacokinetics Drug Carriers drug delivery system liposome Liposomes long-circulating liposome Male Medical sciences Mice Mice, Inbred BALB C Neoplasms, Experimental - drug therapy Pharmacology. Drug treatments poly (ethylene glycol) Polyethylene Glycols - administration & dosage |
| Title | Antitumor Activity of Doxorubicin Encapsulated in Poly (ethylene glycol)-Coated Liposomes |
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