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

M. Hirai; H. Minematsu; Y. Hiramatsu; H. Kitagawa; T. Otani; S. Iwashita; Takayuki Kudoh; L. Chen; Y. Li; M. Okada; D. S. Salomon; K. Igarashi; M. Chikuma; M. Seno

doi:10.1016/j.ijpharm.2010.02.030

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

M. Hirai, H. Minematsu, Y. Hiramatsu, H. Kitagawa, T. Otani, S. Iwashita, Takayuki Kudoh, L. Chen, Y. Li, M. Okada, D. S. Salomon, K. Igarashi, M. Chikuma, M. Seno

Research output: Contribution to journal › Article › peer-review

55 Citations (Scopus)

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.

Original language	English
Pages (from-to)	274-283
Number of pages	10
Journal	International Journal of Pharmaceutics
Volume	391
Issue number	1-2
DOIs	https://doi.org/10.1016/j.ijpharm.2010.02.030
Publication status	Published - May 2010

Keywords

Cis-diamminedinitratoplatinum (II)
Cisplatin
E-selectin
Liposome
Sialyl Lewis

ASJC Scopus subject areas

Pharmaceutical Science

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Hirai, M., Minematsu, H., Hiramatsu, Y., Kitagawa, H., Otani, T., Iwashita, S., Kudoh, T., Chen, L., Li, Y., Okada, M., Salomon, D. S., Igarashi, K., Chikuma, M., & Seno, M. (2010). Novel and simple loading procedure of cisplatin into liposomes and targeting tumor endothelial cells. International Journal of Pharmaceutics, 391(1-2), 274-283. https://doi.org/10.1016/j.ijpharm.2010.02.030

Hirai, M, Minematsu, H, Hiramatsu, Y, Kitagawa, H, Otani, T, Iwashita, S, Kudoh, T, Chen, L, Li, Y, Okada, M, Salomon, DS, Igarashi, K, Chikuma, M & Seno, M 2010, 'Novel and simple loading procedure of cisplatin into liposomes and targeting tumor endothelial cells', International Journal of Pharmaceutics, vol. 391, no. 1-2, pp. 274-283. https://doi.org/10.1016/j.ijpharm.2010.02.030

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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 LewisX (CDDP-SLX-Lip) because we previously demonstrated Sialyl LewisX 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.",

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AU - Hirai, M.

AU - Minematsu, H.

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AU - Kitagawa, H.

AU - Otani, T.

AU - Iwashita, S.

AU - Kudoh, Takayuki

AU - Chen, L.

AU - Li, Y.

AU - Okada, M.

AU - Salomon, D. S.

AU - Igarashi, K.

AU - Chikuma, M.

AU - Seno, M.

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AB - 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 LewisX (CDDP-SLX-Lip) because we previously demonstrated Sialyl LewisX 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.

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

Abstract

Keywords

ASJC Scopus subject areas

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