Paul Kenneth G, Frigo Timothy B, Groman Jesse Y, Groman Ernest V
Advanced Magnetics, Inc., 61 Mooney Street, Cambridge, Massachusetts 02138-1038, USA.
Bioconjug Chem. 2004 Mar-Apr;15(2):394-401. doi: 10.1021/bc034194u.
Investigation into the effect of the reducing sugar of dextran on formation and stability of dextran-coated ultrasmall superparamagnetic iron oxides (USPIO) has demonstrated that reduction of the terminal reducing sugar can have a significant effect on particle size, coating stability, and magnetic properties. Four aspects of polysaccharide-coated USPIO particle synthesis were investigated: (i) the effect reduction of the terminal polysaccharide sugar has upon polysaccharide usage, particle size, stability, and magnetic susceptibility; (ii) the effect an exogenous reducing sugar can have upon particle synthesis; (iii) the effect the molecular weight of the reduced polysaccharide has on particle synthesis; and (iv) the effectiveness of reduced and native dextrans in stabilizing a preformed magnetic sol. For low molecular weight dextrans (MW <or=10 kDa), reduction resulted in a 10 fold or greater decrease in the carbohydrate-to-iron ratio necessary during particle formation to produce the desired particle size (<20 nm). Particles prepared at the equivalent dextran-to-iron ratio using the equivalent native dextrans yielded larger particles except for a 70 kDa dextran where reduced and native dextran yielded identical particles with respect to size and magnetic properties. The stability of particle size and coating was studied using 10 kDa native and reduced dextran. Particles prepared with reduced dextran yielded a more stable coating as evidenced by stability on autoclaving. For native dextrans (MW < 70 kDa), small (<or=30 nm) particles could be obtained at much higher dextran-to-iron ratios, but only the 10 kDa dextran gave a particle with comparable magnetic properties (susceptibility > 20,000 x 10(-6) cgs). Similar results were obtained with a 12 kDa pullulan. The effect of polysaccharide molecular weight on particle size was studied, wherein higher molecular weight reduced dextrans produced larger particles. The effectiveness of the reduced and native dextrans in stabilizing a preformed magnetic sol was compared. Reduced dextrans were found to be superior for stabilizing the magnetic sol. The observed effects of reduction of the terminal sugar in dextran compared with the native dextran were modeled using the Langmuir adsorption isotherm. A good fit of experimental data with this model was found.
对葡聚糖还原糖对葡聚糖包被的超小超顺磁性氧化铁（USPIO）形成及稳定性影响的研究表明，末端还原糖的还原对粒径、包被稳定性和磁性有显著影响。研究了多糖包被的USPIO颗粒合成的四个方面：（i）末端多糖糖的还原对多糖用量、粒径、稳定性和磁化率的影响；（ii）外源性还原糖对颗粒合成的影响；（iii）还原多糖的分子量对颗粒合成的影响；（iv）还原葡聚糖和天然葡聚糖对稳定预制磁溶胶的有效性。对于低分子量葡聚糖（MW≤10 kDa），还原导致形成所需粒径（<20 nm）的颗粒时所需的碳水化合物与铁的比例降低10倍或更多。使用等量天然葡聚糖以等量葡聚糖与铁的比例制备的颗粒产生更大的颗粒，但对于70 kDa的葡聚糖，还原葡聚糖和天然葡聚糖在尺寸和磁性方面产生相同的颗粒。使用10 kDa天然和还原葡聚糖研究了粒径和包被的稳定性。用还原葡聚糖制备的颗粒产生更稳定的包被，高压灭菌后的稳定性证明了这一点。对于天然葡聚糖（MW<70 kDa），在高得多的葡聚糖与铁的比例下可以获得小（≤30 nm）颗粒，但只有10 kDa的葡聚糖产生具有可比磁性（磁化率>20,000×10⁻⁶ cgs）的颗粒。用12 kDa的支链淀粉也得到了类似的结果。研究了多糖分子量对粒径的影响，其中较高分子量的还原葡聚糖产生更大的颗粒。比较了还原葡聚糖和天然葡聚糖对稳定预制磁溶胶的有效性。发现还原葡聚糖在稳定磁溶胶方面更优越。使用朗缪尔吸附等温线对葡聚糖中末端糖还原与天然葡聚糖相比观察到的影响进行了建模。发现实验数据与该模型拟合良好。
