| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Cancer Research Institute [S. K. H., D. P.] and Department of Pharmacology [D. P.], University of California, San Francisco, California 94143-0128; Departments of Experimental Pathology and Experimental Therapeutics [E. M.] and Department of Nuclear Medicine [S. G.], Roswell Park Cancer Institute Buffalo, New York 14263; and Liposome Technology Inc., Menlo Park, California 94025 [D. D. L., F. J. M.]
2 To whom requests for reprints should be addressed, at Cancer Research Institute, Box 128, University of California, San Francisco, CA 94143.
Three different liposome types were compared for blood clearance and tissue uptake in mice bearing C-26 colon carcinoma growing either s.c. or in liver. Therapeutic experiments were performed with the liposome preparation showing the highest tumor uptake. Liposomes were composed of solid-phase phosphatidylcholine, either distearoyl phosphatidylcholine or hydrogenated soy phosphatidylcholine, and cholesterol at a 2:1 molar ratio. These liposomes were compared with similar but sterically stabilized liposomes (SL) which, in addition, contained either GM1 ganglioside or phosphatidylethanolamine derivatized with poly(ethylene glycol). Pharmacokinetic analysis of drug disposition was based on the areas under the curve for liposome-entrapped 67Ga uptake per gram of tissue up to 96 h following i.v. injection. The highest tissue area under the curve values with both liposome types were obtained in spleen, liver, and tumor. However, the sterically stabilized liposomes gave an area under the curve value 2-3-fold higher in the s.c. tumor and about 2-fold lower in liver and spleen. The therapeutic efficacy of doxorubicin (DOX) and epirubicin (EPI) encapsulated in poly(ethylene glycol)-derivatized phosphatidylethanolamine-containing liposomes was compared with that of free drug at two doses, 6 and 9 (or 10) mg/kg animal weight. Liposomes containing drug were injected either as a single dose, at different times following tumor implantation, or as three weekly doses starting 10 days after implantation. When injected as a single dose, liposome-encapsulated DOX had the maximal effect on tumor growth when injected 6 to 9 days after tumor implantation. When injected as three weekly doses, with treatment starting with a delay of 10 days, tumors which had grown to a size of 
0.05–0.1 cm3 regressed in groups of animals treated with either liposome-encapsulated drug (SL-DOX or SL-EPI) but continued to grow unabated in untreated mice and in mice receiving either of the free drugs. Survival of tumor-bearing animals treated with either SL-EPI or SL-DOX was significantly prolonged. Animals receiving saline, EPI, or DOX survived a mean of 50, 62, and 49 days, respectively, following tumor implantation. Eight of nine and nine of 10 animals receiving 6 and 9 mg/kg SL-EPI, respectively, survived to 120 days. Ten of 10 animals in both groups receiving 6 and 9 mg/kg SL-DOX survived to 120 days. None of the surviving animals in the SL-EPI and SL-DOX group showed any histological evidence of tumor at the conclusion of the experiment (120 days). These data show that EPI and DOX encapsulated in sterically stabilized liposomes are significantly more active against C-26 colon carcinoma than is free drug. These two drugs appear to have similar potency under the experimental conditions used in this study.
1 This work was supported by NIH Grant CA 25526-07A3 and American Cancer Society Grant RD264.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 3/30/92. Accepted 10/ 5/92.
This article has been cited by other articles:
|
|
 |
|
  L. E. Harrison, M. Bryan, L. Pliner, and T. Saunders Phase I Trial of Pegylated Liposomal Doxorubicin with Hyperthermic Intraperitoneal Chemotherapy in Patients Undergoing Cytoreduction for Advanced Intra-abdominal Malignancy Ann. Surg. Oncol., May 1, 2008; 15(5): 1407 - 1413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Lee, E. R. Gillies, M. E. Fox, S. J. Guillaudeu, J. M. J. Frechet, E. E. Dy, and F. C. Szoka A single dose of doxorubicin-functionalized bow-tie dendrimer cures mice bearing C-26 colon carcinomas PNAS, November 7, 2006; 103(45): 16649 - 16654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. B. Kirpotin, D. C. Drummond, Y. Shao, M. R. Shalaby, K. Hong, U. B. Nielsen, J. D. Marks, C. C. Benz, and J. W. Park Antibody Targeting of Long-Circulating Lipidic Nanoparticles Does Not Increase Tumor Localization but Does Increase Internalization in Animal Models. Cancer Res., July 1, 2006; 66(13): 6732 - 6740. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Gabizon, D. Tzemach, A. T. Horowitz, H. Shmeeda, J. Yeh, and S. Zalipsky Reduced toxicity and superior therapeutic activity of a mitomycin C lipid-based prodrug incorporated in pegylated liposomes. Clin. Cancer Res., March 15, 2006; 12(6): 1913 - 1920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Arnold, D. E. Mager, J. E. Slack, and R. M. Straubinger Effect of Repetitive Administration of Doxorubicin-Containing Liposomes on Plasma Pharmacokinetics and Drug Biodistribution in a Rat Brain Tumor Model Clin. Cancer Res., December 15, 2005; 11(24): 8856 - 8865. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-Y. Lee, H.-C. Wu, Y.-L. Tseng, and C.-T. Lin A Novel Peptide Specifically Binding to Nasopharyngeal Carcinoma For Targeted Drug Delivery Cancer Res., November 1, 2004; 64(21): 8002 - 8008. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Nishiyama, S. Okazaki, H. Cabral, M. Miyamoto, Y. Kato, Y. Sugiyama, K. Nishio, Y. Matsumura, and K. Kataoka Novel Cisplatin-Incorporated Polymeric Micelles Can Eradicate Solid Tumors in Mice Cancer Res., December 15, 2003; 63(24): 8977 - 8983. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Snyder, W. R. Greco, D. A. Bellnier, L. Vaughan, and B. W. Henderson Photodynamic Therapy: A Means to Enhanced Drug Delivery to Tumors Cancer Res., December 1, 2003; 63(23): 8126 - 8131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Lee, T. Tanaka, T. Murai, M. Kondo, J. Kimura, W. Su, T. Kitagawa, T. Ito, H. Matsuda, and M. Miyasaka Novel Chondroitin Sulfate-binding Cationic Liposomes Loaded with Cisplatin Efficiently Suppress the Local Growth and Liver Metastasis of Tumor Cells in Vivo Cancer Res., August 1, 2002; 62(15): 4282 - 4288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zhou, R. Mazurchuk, and R. M. Straubinger Antivasculature Effects of Doxorubicin-containing Liposomes in an Intracranial Rat Brain Tumor Model Cancer Res., May 1, 2002; 62(9): 2561 - 2566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Park, K. Hong, D. B. Kirpotin, G. Colbern, R. Shalaby, J. Baselga, Y. Shao, U. B. Nielsen, J. D. Marks, D. Moore, et al. Anti-HER2 Immunoliposomes: Enhanced Efficacy Attributable to Targeted Delivery Clin. Cancer Res., April 1, 2002; 8(4): 1172 - 1181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. Marina, D. Cochrane, E. Harney, K. Zomorodi, S. Blaney, N. Winick, M. Bernstein, and M. P. Link Dose Escalation and Pharmacokinetics of Pegylated Liposomal Doxorubicin (Doxil) in Children with Solid Tumors: A Pediatric Oncology Group Study Clin. Cancer Res., February 1, 2002; 8(2): 413 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tamagawa, K. Shimizu, T. Ebine, Y. Maitani, T. Fukui, K.-i. Kawai, and N. Takahashi Antitumor Efficacy in Vitro and in Vivo of Falconensones, a New Type of Polyene Clin. Cancer Res., November 1, 2001; 7(11): 3551 - 3558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Sparano, U. Malik, L. Rajdev, C. Sarta, U. Hopkins, and A. C. Wolff Phase I Trial of Pegylated Liposomal Doxorubicin and Docetaxel in Advanced Breast Cancer J. Clin. Oncol., June 15, 2001; 19(12): 3117 - 3125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. PERVAIZ Reactive oxygen-dependent production of novel photochemotherapeutic agents FASEB J, March 1, 2001; 15(3): 612 - 617. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Emfietzoglou, K. Kostarelos, and G. Sgouros An Analytic Dosimetry Study for the Use of Radionuclide-Liposome Conjugates in Internal Radiotherapy J. Nucl. Med., March 1, 2001; 42(3): 499 - 504. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. T. M. Dams, P. Laverman, W. J. G. Oyen, G. Storm, G. L. Scherphof, J. W. M. van der Meer, F. H. M. Corstens, and O. C. Boerman Accelerated Blood Clearance and Altered Biodistribution of Repeated Injections of Sterically Stabilized Liposomes J. Pharmacol. Exp. Ther., March 1, 2000; 292(3): 1071 - 1079. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. C. Drummond, O. Meyer, K. Hong, D. B. Kirpotin, and D. Papahadjopoulos Optimizing Liposomes for Delivery of Chemotherapeutic Agents to Solid Tumors Pharmacol. Rev., December 1, 1999; 51(4): 691 - 744. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Fielding, L. Moon-Mcdermott, R. O. Lewis, and M. J. Horner Pharmacokinetics and Urinary Excretion of Amikacin in Low-Clearance Unilamellar Liposomes after a Single or Repeated Intravenous Administration in the Rhesus Monkey Antimicrob. Agents Chemother., March 1, 1999; 43(3): 503 - 509. [Abstract] [Full Text]
|
|
|
|
 |
|
 M Amantea, M S Newman, T M Sullivan, A Forrest, and P K Working Relationship of dose intensity to the induction of palmar-plantar erythrodysesthia by pegylated liposomal doxorubicin in dogs Human and Experimental Toxicology, January 1, 1999; 18(1): 17 - 26. [Abstract] [PDF]
|
|
|
|
|
|
M. J. Parr, D. Masin, P. R. Cullis, and M. B. Bally Accumulation of Liposomal Lipid and Encapsulated Doxorubicin in Murine Lewis Lung Carcinoma: The Lack of Beneficial Effects by Coating Liposomes with Poly(ethylene glycol) J. Pharmacol. Exp. Ther., March 1, 1997; 280(3): 1319 - 1327. [Abstract] [Full Text]
|
|
|
|
|
|
L. D. Mayer, G. Dougherty, T. O. Harasym, and M. B. Bally The Role of Tumor-Associated Macrophages in the Delivery of Liposomal Doxorubicin to Solid Murine Fibrosarcoma Tumors J. Pharmacol. Exp. Ther., March 1, 1997; 280(3): 1406 - 1414. [Abstract] [Full Text]
|
|
|
|
 |
|
 F. D. Cirisano and B. Y. Karlan The Role of the HER-2/neu Oncogene in Gynecologic Cancers Reproductive Sciences, May 1, 1996; 3(3): 99 - 105. [Abstract] [PDF]
|
|
|
|
 |
|
 D. Lasic and D Papahadjopoulos Liposomes revisited Science, March 3, 1995; 267(5202): 1275 - 1276. [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
