Tyner Katherine M, Schiffman Scott R, Giannelis Emmanuel P
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
J Control Release. 2004 Mar 24;95(3):501-14. doi: 10.1016/j.jconrel.2003.12.027.
A novel method of delivering non-ionic, poorly water-soluble drugs such as campthothecin was developed. Camptothecin was first incorporated into micelles derived from negatively charged surfactants. The negatively charged micelles were then encapsulated in nanoparticles of magnesium-aluminum layered double hydroxides (LDHs) by an ion exchange process. The resulting nanobiohybrids released camptothecin rapidly with complete release within 10 min at both pH 4.8 and 7.2. The LDH complex with carmine released carmine within 30 min at pH 4.8, but took over 70 days at pH 7.2. When administered to Glioma cells in vitro, the nanobiohybrid containing camptothecin resulted in significantly lower survival times compared to untreated cells, or to cells incubated with the surfactant, the pristine LDH, or water (delivery medium). The encapsulation method allowed for an approximately threefold increase in solubility of camptothecin. In addition, the modification of the surface of the LDH provided potential site-directing of the nanohybrids. These enhancements to the delivery scheme suggest the potential use of these hybrids for a variety of drug therapies.
开发了一种递送非离子型、水溶性差的药物(如喜树碱)的新方法。首先将喜树碱掺入由带负电荷的表面活性剂衍生的胶束中。然后通过离子交换过程将带负电荷的胶束封装在镁铝层状双氢氧化物(LDH)纳米颗粒中。所得的纳米生物杂化物在pH 4.8和7.2时均在10分钟内快速释放喜树碱,且完全释放。与胭脂红形成的LDH复合物在pH 4.8时30分钟内释放胭脂红,但在pH 7.2时需要70多天。当在体外给予胶质瘤细胞时,与未处理的细胞相比,含有喜树碱的纳米生物杂化物导致存活时间显著缩短,与用表面活性剂、原始LDH或水(递送介质)孵育的细胞相比也是如此。这种封装方法使喜树碱的溶解度提高了约三倍。此外,LDH表面的修饰为纳米杂化物提供了潜在的位点导向。这些对递送方案的改进表明这些杂化物在多种药物治疗中的潜在用途。