Development of a novel drug delivery system consisting of an antitumor agent tocopheryl succinate

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• 作者：Susumu Hama ; Satoru Utsumi ; Yuki Fukuda ; Kayoko Nakayama ; Yuriko Okamura ; Hiroyuki Tsuchiya ; Kenji Fukuzawa ; Hedeyoshi Harashima ; Kentaro Kogure
• 关键词：Tocopheryl succinate ; Nanovesicles ; Tumor suppression
• 刊名：Journal of Controlled Release
• 出版年：2012
• 出版时间：10 August, 2012
• 年：2012
• 卷：161
• 期：3
• 页码：843-851
• 全文大小：1001 K

文摘

We have developed a novel drug delivery system (DDS) using an antitumor agent, ¦Á-tocopheryl succinate (TS). TS has attracted attention as a unique anti-cancer drug for its ability to induce apoptosis in various cancer cells. Furthermore, TS itself readily forms nanovesicles (TS-NVs) and is a prospective tool for use as an antitumor DDS. However, TS-NVs are unstable for encapsulating drugs and passive targeting delivery to tumor tissue via enhanced permeation and retention effect. Therefore, to improve the stability of vesicles, we developed a novel nanovesicle consisting of TS and egg phosphatidylcholine (TS-EPC-NVs). The stability of vesicles of TS-EPC-NVs was significantly higher than that of TS-NVs. As a result, the in vivo antitumor activity of TS-EPC-NVs was more potent than that of TS-NVs. The enhanced antitumor activity of TS-EPC-NVs was found to be due to its effective intratumoral distribution. Moreover, the in vitro anticancer efficiency of TS-EPC-NVs increased seven-fold. We suggest that the improvement is due to homogenous cellular uptake and enhanced cytosolic delivery of the nanovesicles via alteration of intracellular trafficking. Furthermore, TS-EPC-NVs encapsulating siRNA showed significant knockdown efficiency. In summary, TS-EPC-NVs represent a novel and attractive drug delivery system. The system shows antitumor activity of the encapsulated drug and the carrier itself.