Biomedical Engineering Center, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China.
J Biomed Nanotechnol. 2009 Oct;5(5):557-64. doi: 10.1166/jbn.2009.1073.
In this paper, a chitosan-methotrexate covalently conjugated nanoparticles (CS-MTX-TPP NPs) has been developed as a potential delivery system for methotrexate (MTX). MTX was first conjugated to CS by using glutaraldehyde as cross-linked agent, and followed by the process of ionic gelation between MTX-conjugated CS and sodium tripolyphosphate (TPP) to form CS-MTX-TPP NPs at mild reaction conditions. The hydrodynamic diameter of CS-MTX-TPP NPs and the encapsulation efficiency of MTX were affected by the weight ratio of MTX/CS. At the ratio of 1/11, the mean hydrodynamic diameter of CS-MTX-TPP NPs was the lowest (187.9 +/- 9.0 nm) and the nanoparticles presented the encapsulation efficiency of MTX with 53.0 +/- 3.2%. The characterizations by atomic force microscopy (AFM) and photon correlation spectroscopy (PCS) showed the CS-MTX-TPP NPs had a spherical shape and good dispersion with diameter of sub-200-nm and zeta potential of 30 mV. Additionally, in vitro release test revealed that the stable covalent bonding of CS and MTX was beneficial for providing slow release for MTX. Especially, cellular toxicity study in MCF-7 cancer cells further demonstrated the effective anticancer efficacy of this new type of delivery for MTX.
本文制备了一种壳聚糖-甲氨蝶呤共价连接的纳米粒子（CS-MTX-TPP NPs），作为甲氨蝶呤（MTX）的潜在递送系统。首先，通过戊二醛作为交联剂将 MTX 连接到 CS 上，然后在温和的反应条件下，通过 MTX 修饰的 CS 与三聚磷酸钠（TPP）之间的离子凝胶化过程形成 CS-MTX-TPP NPs。CS-MTX-TPP NPs 的水动力学直径和 MTX 的包封效率受 MTX/CS 重量比的影响。当比例为 1/11 时，CS-MTX-TPP NPs 的平均水动力学直径最低（187.9 ± 9.0nm），纳米粒的 MTX 包封效率为 53.0 ± 3.2%。原子力显微镜（AFM）和光相关光谱（PCS）的表征表明，CS-MTX-TPP NPs 呈球形，具有良好的分散性，粒径在 200nm 以下，Zeta 电位为 30mV。此外，体外释放试验表明 CS 和 MTX 的稳定共价键合有利于 MTX 的缓慢释放。特别是在 MCF-7 癌细胞中的细胞毒性研究进一步证明了这种新型 MTX 递药系统的有效抗癌功效。
