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羟丙基-β-环糊精强化的紫杉醇固体脂质纳米粒作为口服给药系统。

Solid lipid nanoparticles of paclitaxel strengthened by hydroxypropyl-β-cyclodextrin as an oral delivery system.

机构信息

College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Yuseonggu, Daejeon 305-764, Republic of Korea.

出版信息

Int J Mol Med. 2012 Oct;30(4):953-9. doi: 10.3892/ijmm.2012.1086. Epub 2012 Aug 3.

Abstract

The objective of this study was to evaluate the potential of surface-modified paclitaxel (PTX)-incorporated solid lipid nanoparticles with hydroxypropyl-β-cyclodextrin (smPSH). The smPSH released 89.70 ± 3.99% of its entrapped PTX within 24 h when placed in dissolution medium containing sodium lauryl sulfate. The cellular uptake of PTX from smPSH in Caco-2 cells was 5.3-fold increased compared to a PTX solution based on a Taxol formulation. Moreover, smPSH showed an increased cytotoxicity compared to PTX solution. In addition, AUC (5.43 µg•h/ml) and Cmax (1.44 µg/ml) of smPSH were higher than those (1.81 µg•h/ml and 0.73 µg/ml) of PTX solution. The drug concentration of smPSH (11.12 ± 4.45 ng/mg of lymph tissue) in lymph nodes was higher than that of the PTX solution (0.89 ± 0.75 ng/mg of lymph tissue), suggesting that more PTX was transported to the lymphatic vessels in the form of smPSH. In conclusion, smPSH have a potential as an alternative delivery system for oral administration of PTX.

摘要

本研究旨在评估载紫杉醇(PTX)的表面修饰固体脂质纳米粒与羟丙基-β-环糊精(smPSH)的潜力。当将 smPSH 置于含有十二烷基硫酸钠的溶解介质中时,其包封的 PTX 在 24 小时内释放了 89.70±3.99%。与基于 Taxol 制剂的 PTX 溶液相比,smPSH 中 PTX 在 Caco-2 细胞中的细胞摄取增加了 5.3 倍。此外,smPSH 显示出比 PTX 溶液更高的细胞毒性。此外,smPSH 的 AUC(5.43µg•h/ml)和 Cmax(1.44µg/ml)均高于 PTX 溶液(1.81µg•h/ml 和 0.73µg/ml)。淋巴结中 smPSH(11.12±4.45ng/mg 淋巴组织)的药物浓度高于 PTX 溶液(0.89±0.75ng/mg 淋巴组织),这表明更多的 PTX 以 smPSH 的形式被转运到淋巴管中。总之,smPSH 具有作为 PTX 口服给药的替代递药系统的潜力。

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