Novel and simple loading procedure of cisplatin into liposomes and targeting tumor endothelial cells

Novel and simple loading procedure of cisplatin into liposomes and targeting tumor endothelial cells Although intravenous administration of high levels of cisplatin (CDDP) are limited due to its severe side effects, efficient delivery of CDDP directly to the tumor should improve the therapeutic response while potentially by-passing significant side effects. High loading of CDDP into liposomes is one technique that could be used as a potential drug delivery system. Since cis -diamminedinitratoplatinum (CDDP3) is highly soluble in water and converts to CDDP in the presence of chloride ions, we encapsulated CDDP3 into liposomes in the absence of chloride ions and supplemented chloride ions to prepare CDDP-encapsulated liposomes (CDDP-Lip) resulting in a significantly improved loading efficiency of CDDP. We further conjugated the CDDP-Lip with Sialyl Lewis X (CDDP-SLX-Lip) because we previously demonstrated Sialyl Lewis X enhanced efficient accumulation of liposomes into tumors in vivo. CDDP-SLX-Lip treated mice showed a survival rate of 75% at 14 days even if a lethal level of CDDP was injected into mice. Loss of body weight was negligible and no histological abnormality was found in a variety of normal tissues. Accumulation of CDDP-SLX-Lip was about 6 times more than that of CDDP-Lip or CDDP. As the result, there was better antitumor activity of CDDP-SLX-Lip than that of CDDP-Lip with significantly less toxic effects in normal tissues. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png International Journal of Pharmaceutics Elsevier

Novel and simple loading procedure of cisplatin into liposomes and targeting tumor endothelial cells

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Publisher
Elsevier
Copyright
Copyright © 2010 Elsevier B.V.
ISSN
0378-5173
D.O.I.
10.1016/j.ijpharm.2010.02.030
Publisher site
See Article on Publisher Site

Abstract

Although intravenous administration of high levels of cisplatin (CDDP) are limited due to its severe side effects, efficient delivery of CDDP directly to the tumor should improve the therapeutic response while potentially by-passing significant side effects. High loading of CDDP into liposomes is one technique that could be used as a potential drug delivery system. Since cis -diamminedinitratoplatinum (CDDP3) is highly soluble in water and converts to CDDP in the presence of chloride ions, we encapsulated CDDP3 into liposomes in the absence of chloride ions and supplemented chloride ions to prepare CDDP-encapsulated liposomes (CDDP-Lip) resulting in a significantly improved loading efficiency of CDDP. We further conjugated the CDDP-Lip with Sialyl Lewis X (CDDP-SLX-Lip) because we previously demonstrated Sialyl Lewis X enhanced efficient accumulation of liposomes into tumors in vivo. CDDP-SLX-Lip treated mice showed a survival rate of 75% at 14 days even if a lethal level of CDDP was injected into mice. Loss of body weight was negligible and no histological abnormality was found in a variety of normal tissues. Accumulation of CDDP-SLX-Lip was about 6 times more than that of CDDP-Lip or CDDP. As the result, there was better antitumor activity of CDDP-SLX-Lip than that of CDDP-Lip with significantly less toxic effects in normal tissues.

Journal

International Journal of PharmaceuticsElsevier

Published: May 31, 2010

References

  • Improvement of cis -dichlorodiammineplatinum therapeutic index in an animal model
    Cvitkovic, E.; Spaulding, J.; Bethune, V.; Martin, J.; Whitmore, W.F.
  • High dose cis -platinum diammine dichloride: amelioration of renal toxicity by mannitol diuresis
    Hayes, D.M.; Cvitkovic, E.; Golbey, R.B.; Scheiner, E.; Helson, L.; Krakoff, I.H.
  • Accumulation of liposome with Sialyl Lewis X to inflammation and tumor region: application to in vivo bio-imaging
    Hirai, M.; Minematsu, H.; Kondo, N.; Oie, K.; Igarashi, K.; Yamazaki, N.
  • Comparative pharmacokinetics, tissue distribution, and therapeutic effectiveness of cisplatin encapsulated in long-circulating, pegylated liposomes (SPI-077) in tumor-bearing mice
    Newman, M.S.; Colbern, G.T.; Working, P.K.; Engbers, C.; Amantea, M.A.
  • Mechanisms that regulate the function of the selectins and their ligands
    Vestweber, D.; Blanks, J.E.

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