A self-assembled nanocarrier loading teniposide improves the oral delivery and drug concentration in tumor.
A self-assembled nanocarrier loading teniposide improves the oral delivery and drug concentration in tumor.
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DOI：
10.1016/j.jconrel.2012.12.018
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发表时间：
2013-02
期刊：
影响因子：
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通讯作者：
Zhiwen Zhang;Li Ma;Shijun Jiang;Zeying Liu;Jian Huang;Lingli Chen;Haijun Yu;Yaping Li
中科院分区：
文献类型：
--
作者：
Zhiwen Zhang;Li Ma;Shijun Jiang;Zeying Liu;Jian Huang;Lingli Chen;Haijun Yu;Yaping Li
We attempted to improve the oral delivery of lipophilic teniposide to achieve higher drug concentration in tumor by self-assembled nanocarrier for further oral chemotherapy. The teniposide loaded self-assembled nanocarrier (TSN) was spherical nanometric particles with narrow size distribution. The intestinal absorption of teniposide from TSN was obviously improved 4.09- and 6.35-fold in duodenum and jejunum at 0.5h after oral administration, then significantly decreased with the prolongation of time. The cellular uptake of TSN in Caco-2 cell monolayer was significantly enhanced over 3 folds and increased with incubation time. Moreover, TSN could be internalized into Caco-2 cell monolayer through clathrin-mediated endocytosis pathway, and then mainly transported into the systemic circulation via portal vein and intestinal lymphatic pathway. The pharmacokinetic results indicated that the AUC0-tvalue of TSN in rats was significantly improved 5.41-fold than that of teniposide solution, moreover, the teniposide concentration in tumor from TSN was obviously improved over 7-fold in tumor bearing mice. The captured image indicated that the oral administered TSN could specifically accumulate in tumor in the xenograft model. Therefore, the self-assembled nanocarrier was promising to enhance the oral delivery of lipophilic teniposide and its concentration in tumor for oral chemotherapy.
