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

被引：46

作者：

Hirai, M. ^{[2
]}

Minematsu, H. ^{[2
]}

Hiramatsu, Y. ^{[2
]}

Kitagawa, H. ^{[2
]}

Otani, T. ^{[2
]}

Iwashita, S. ^{[2
]}

Kudoh, T.

Chen, L.

Li, Y.

Okada, M.

Salomon, D. S. ^{[3
]}

Igarashi, K. ^{[2
]}

Chikuma, M. ^{[4
]}

Seno, M. ^{[1
]}

机构：

[1] Okayama Univ, Grad Sch Nat Sci & Technol, Dept Med & Bioengn Sci, Lab Nanobiotechnol,Kita Ku, Okayama 7008530, Japan

[2] Katayama Chem Ind Co LTD, R&D Div, Osaka 5620015, Japan

[3] NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA

[4] Osaka Univ Pharmaceut Sci, Osaka 569109, Japan

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2010年 / 391卷 / 1-2期

关键词：

Cisplatin; Cis-diamminedinitratoplatinum (II); Liposome; E-selectin; Sialyl Lewis(x); LONG-CIRCULATING LIPOSOMES; STEALTH LIPOSOMES; THERAPEUTIC INDEX; MICE BEARING; E-SELECTIN; PHASE-I; CANCER; PHARMACOKINETICS; ACCUMULATION; CARCINOMA;

D O I：

10.1016/j.ijpharm.2010.02.030

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 COOP. 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. (C) 2010 Elsevier B.V. All rights reserved.

引用

页码：274 / 283

页数：10

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