論文 - 詳細
| RRC ID | 69603 |
|---|---|
| 著者 | 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. |
| タイトル | Novel and simple loading procedure of cisplatin into liposomes and targeting tumor endothelial cells. |
| ジャーナル | Int J Pharm |
| 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. |
| 巻・号 | 391(1-2) |
| ページ | 274-83 |
| 公開日 | 2010-5-31 |
| DOI | 10.1016/j.ijpharm.2010.02.030 |
| PII | S0378-5173(10)00171-7 |
| PMID | 20211714 |
| MeSH | Animals Antineoplastic Agents / administration & dosage* Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacokinetics Cell Line, Tumor Cells, Cultured Cisplatin / administration & dosage* Cisplatin / chemistry Cisplatin / pharmacokinetics Drug Delivery Systems / adverse effects Drug Delivery Systems / methods* E-Selectin / metabolism Female Liposomes* Mice Mice, Inbred BALB C Oligosaccharides / administration & dosage* Oligosaccharides / chemistry Sialyl Lewis X Antigen Survival Rate Xenograft Model Antitumor Assays |
| IF | 4.845 |
| リソース情報 | |
| ヒト・動物細胞 | Ehrlich(RCB0142) |