Hu Fu-Qiang, Ren Guo-Fei, Yuan Hong, Du Yong-Zhong, Zeng Su
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, PR China.
Colloids Surf B Biointerfaces. 2006 Jul 1;50(2):97-103. doi: 10.1016/j.colsurfb.2006.04.009. Epub 2006 May 5.
Stearic acid grafted chitosan oligosaccharide (CSO-SA) with different degree of amino substitution (SD) was synthesized by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-mediated coupling reaction. The critical micelle concentration (CMC) of CSO-SA with different SD was about 0.06, 0.04, 0.01 mg/ml, respectively. With the increase of micelle concentration, the micelle size decreased, and the zeta potential increased. On the other hand, with the increase of SD of CSO-SA, the micelle size and zeta potential decreased due to the increased hydrophobic interaction of SA and the reduced free amino groups. To increase the stability of the micelle in vivo and controll drug release, the shells of micelles were cross-linked by glutaraldehyde. By controlling the molar ratio of CSO-SA to glutaraldehyde, the cross-linking of intra-micelle could be reached, and the nanoparticle with smaller size than that of its initial micelle was obtained. Paclitaxel was then used as model drug to incorporate into the micelles, and the surfaces of the micelles were further cross-linked by glutaraldehyde to form drug loaded and shell cross-linked nanoparticles. The effects of drug loading, SD of CSO-SA and cross-link degree on the size, zeta potential, drug entrapment efficiency and in vitro drug release behavior of micelles and its cross-linked nanoparticles were investigated. The higher drug entrapment efficiencies (above 94%) were observed in all case. The charged amounts of drug did not affect the drug release behavior. The drug release rate decreased with the increase of SD of CSO-SA and cross-link degree.
通过1-乙基-3-(3-二甲基氨基丙基)碳二亚胺(EDC)介导的偶联反应合成了具有不同氨基取代度(SD)的硬脂酸接枝壳寡糖(CSO-SA)。不同SD的CSO-SA的临界胶束浓度(CMC)分别约为0.06、0.04、0.01mg/ml。随着胶束浓度的增加，胶束尺寸减小，zeta电位增加。另一方面，随着CSO-SA的SD增加，由于SA疏水相互作用增强和游离氨基减少，胶束尺寸和zeta电位降低。为提高胶束在体内的稳定性并控制药物释放，用戊二醛对胶束壳进行交联。通过控制CSO-SA与戊二醛的摩尔比，可实现胶束内交联，得到尺寸比初始胶束更小的纳米颗粒。然后以紫杉醇为模型药物包载于胶束中，并用戊二醛进一步交联胶束表面，形成载药且壳交联的纳米颗粒。考察了载药量、CSO-SA的SD和交联度对胶束及其交联纳米颗粒的尺寸、zeta电位、药物包封率和体外药物释放行为的影响。在所有情况下均观察到较高的药物包封率(高于94%)。药物的电荷量不影响药物释放行为。药物释放速率随CSO-SA的SD和交联度的增加而降低。
