Center for Intelligent Nano- Bio Materials (CINBM), Department of Bioinspired Science and Department of Chemistry and Nano Science (Ewha Global Top 5 program-2011), Ewha Womans University, Seoul 120-750, Republic of Korea.
Curr Pharm Des. 2013;19(41):7196-202. doi: 10.2174/138161281941131219123718.
A methotrexate (MTX)-loaded layered double hydroxide (LDH) nanoparticle system was synthesized by intercalating MTX into the interlayer spaces of LDH. In vivo pharmacokinetic study demonstrated that the MTX-LDH hybrid had similar kinetic behaviors as free MTX, showing a rapid decline in the plasma MTX level, with characteristics of a biexponential function. However, the hybrid system remarkably suppressed tumor growth in human osteosarcoma-bearing mice compared to an equivalent amount of free MTX. Using MTX-LDH nanoparticles, a significantly high amount of MTX was delivered to target tumor tissue, whereas a low level was found in normal tissues. Moreover, LDH nanocarriers did not accumulate in any specific tissue nor cause acute toxicity up to the applied dose for the hybrid system. These results suggest that the MTX-LDH nanohybrid system has great potential as an anti-cancer drug with enhanced in vivo anti-tumor activity and bioavailability in target tumor tissue along with reduced side effects.
甲氨蝶呤（MTX）负载层状双氢氧化物（LDH）纳米粒子系统是通过将 MTX 嵌入 LDH 的层间空间来合成的。体内药代动力学研究表明，MTX-LDH 杂化物具有与游离 MTX 相似的动力学行为，表现出血浆 MTX 水平的快速下降，具有双指数函数的特征。然而，与等量的游离 MTX 相比，该杂化系统显著抑制了人骨肉瘤荷瘤小鼠的肿瘤生长。使用 MTX-LDH 纳米粒子，大量的 MTX 被递送到靶肿瘤组织，而在正常组织中发现的 MTX 水平较低。此外，LDH 纳米载体不会在任何特定组织中积累，也不会在应用于杂化系统的剂量范围内引起急性毒性。这些结果表明，MTX-LDH 纳米杂化物系统具有作为抗癌药物的巨大潜力，可增强体内抗肿瘤活性和靶肿瘤组织中的生物利用度，同时降低副作用。
