Ding Yongling, Shen Shirley Z, Sun Huadong, Sun Kangning, Liu Futian, Qi Yushi, Yan Jun
Key Laboratory for Liquid-solid Structural Evolution and Processing of Materials (Ministry of Education), Engineering Ceramics Key Laboratory of Shandong Province, Shandong University, Jinan 250061, PR China; School of Materials Science and Engineering, University of Jinan, Jinan 250022, PR China.
Materials Science & Engineering, CSIRO, Highett Vic 3190, Australia.
Mater Sci Eng C Mater Biol Appl. 2015 Mar;48:487-98. doi: 10.1016/j.msec.2014.12.036. Epub 2014 Dec 9.
In this study, a novel hydrogel, chitosan (CS) crosslinked carboxymethyl-β-cyclodextrin (CM-β-CD) polymer modified Fe3O4 magnetic nanoparticles was synthesized for delivering hydrophobic anticancer drug 5-fluorouracil (CS-CDpoly-MNPs). Carboxymethyl-β-cyclodextrin being grafted on the Fe3O4 nanoparticles (CDpoly-MNPs) contributed to an enhancement of adsorption capacities because of the inclusion abilities of its hydrophobic cavity with insoluble anticancer drugs through host-guest interactions. Experimental results indicated that the amounts of crosslinking agent and bonding times played a crucial role in determining morphology features of the hybrid nanocarriers. The nanocarriers exhibited a high loading efficiency (44.7±1.8%) with a high saturation magnetization of 43.8emu/g. UV-Vis spectroscopy results showed that anticancer drug 5-fluorouracil (5-Fu) could be successfully included into the cavities of the covalently linked CDpoly-MNPs. Moreover, the free carboxymethyl groups could enhance the bonding interactions between the covalently linked CDpoly-MNPs and anticancer drugs. In vitro release studies revealed that the release behaviors of CS-CDpoly-MNPs carriers were pH dependent and demonstrated a swelling and diffusion controlled release. A lower pH value led to swelling effect and electrostatic repulsion contributing to the protonation amine impact of NH3(+), and thus resulted in a higher release rate of 5-Fu. The mechanism of 5-Fu encapsulated into the magnetic chitosan nanoparticles was tentatively proposed.
在本研究中,合成了一种新型水凝胶,即壳聚糖(CS)交联羧甲基-β-环糊精(CM-β-CD)聚合物修饰的Fe3O4磁性纳米颗粒,用于递送疏水性抗癌药物5-氟尿嘧啶(CS-CDpoly-MNPs)。羧甲基-β-环糊精接枝到Fe3O4纳米颗粒(CDpoly-MNPs)上,由于其疏水腔通过主客体相互作用与不溶性抗癌药物的包合能力,有助于提高吸附能力。实验结果表明,交联剂的用量和键合次数在决定杂化纳米载体的形态特征方面起着关键作用。纳米载体表现出高负载效率(44.7±1.8%),饱和磁化强度高达43.8emu/g。紫外-可见光谱结果表明,抗癌药物5-氟尿嘧啶(5-Fu)能够成功地包合到共价连接的CDpoly-MNPs的腔内。此外,游离的羧甲基基团可以增强共价连接的CDpoly-MNPs与抗癌药物之间的键合相互作用。体外释放研究表明,CS-CDpoly-MNPs载体的释放行为依赖于pH值,呈现出溶胀和扩散控制释放。较低的pH值导致溶胀效应和静电排斥,这是由于NH3(+)的质子化胺作用,从而导致5-Fu的释放速率更高。初步提出了5-Fu包封到磁性壳聚糖纳米颗粒中的机制。